Evidence-Based Complementary and Alternative Medicine

Evidence-Based Complementary and Alternative Medicine / 2016 / Article

Review Article | Open Access

Volume 2016 |Article ID 9232593 | https://doi.org/10.1155/2016/9232593

Sensen Chi, Gaimei She, Dan Han, Weihua Wang, Zhao Liu, Bin Liu, "Genus Tinospora: Ethnopharmacology, Phytochemistry, and Pharmacology", Evidence-Based Complementary and Alternative Medicine, vol. 2016, Article ID 9232593, 32 pages, 2016. https://doi.org/10.1155/2016/9232593

Genus Tinospora: Ethnopharmacology, Phytochemistry, and Pharmacology

Academic Editor: Nunziatina De Tommasi
Received03 May 2016
Revised10 Jul 2016
Accepted13 Jul 2016
Published28 Aug 2016


The genus Tinospora includes 34 species, in which several herbs were used as traditional medicines by indigenous groups throughout the tropical and subtropical parts of Asia, Africa, and Australia. The extensive literature survey revealed Tinospora species to be a group of important medicinal plants used for the ethnomedical treatment of colds, headaches, pharyngitis, fever, diarrhea, oral ulcer, diabetes, digestive disorder, and rheumatoid arthritis. Indian ethnopharmacological data points to the therapeutic potential of the T. cordifolia for the treatment of diabetic conditions. While Tinospora species are confusing in individual ingredients and their mechanisms of action, the ethnopharmacological history of those plants indicated that they exhibit antidiabetic, antioxidation, antitumor, anti-inflammation, antimicrobial, antiosteoporosis, and immunostimulation activities. While the clinical applications in modern medicine are lacking convincing evidence and support, this review is aimed at summarizing the current knowledge of the traditional uses, phytochemistry, biological activities, and toxicities of the genus Tinospora to reveal its therapeutic potentials and gaps, offering opportunities for future researches.

1. Introduction

The genus Tinospora (Menispermaceae), 34 species included, is a large glabrous deciduous climbing shrub [1]. The species have been widely distributed throughout the tropical and subtropical parts of Asia, Africa, and Australia. At present, 6 species and 2 varieties are found in China, in which T. hainanensis and T. guangxiensis Lo. as endemic species are mainly distributed in Guangxi and Hainan. T. sinensis and T. capillipes are officially listed in the 2015 edition of the Chinese Pharmacopoeia (中民共国药典) with the Chinese names “Kuan Jin Teng” (宽筋藤) and “Jin Guo Lan” (金果), respectively [2]. Those herbs in genus Tinospora are mostly heat-clearing and detoxifying (清热解). And they are commonly used as domestic folk medicine for the treatment of colds, headaches, pharyngitis, fever, diarrhea, oral ulcer, digestive disorder, and rheumatoid arthritis. For instance, Indian Ayurveda usually employs T. cordifolia in treatment for diabetes. Its obvious antidiabetic properties attract modern researches’ attention [3]. T. sinensis is the major composition in a famous traditional formula “Si Wei Zang Mu Xiang” powder (四味藏), used for the treatment of wind-heat disease (热病) and deficiency-heat syndrome (热证) [3, 4]. This family is a rich source of terpenes and alkaloids; the ongoing exploration for bioactive constituents also revealed the presence of C6-C3 derivatives, polysaccharides, and other components with exact structures. Modern pharmacological researches and clinical practices demonstrated that Tinospora species possess a wide spectrum of activities, including antidiabetic [3], antioxidation [5, 6], antitumor [7, 8], anti-inflammation [9, 10], antimicrobial [11], antiosteoporosis [12], and immunostimulation effect [13]. In clinic, genus Tinospora is commonly used to protect and support the immune system, to prevent upper respiratory infections, to lower oral ulcer, to treat diabetes, to be an adjunctive therapy in cancer, and to protect the liver. However, a systematic review of these studies has not been performed to date. This paper summarized the research achievements of the medicine plants in genus Tinospora ranging from clinical studies to phytochemistry and pharmacology areas. It is expected that such a paper would on one hand serve as an available database for future researches and on the other hand enable experts in the field to determine if the research on genus Tinospora is on proper path.

2. Traditional Uses and Ethnopharmacology

Those species in this genus have traditionally been used as therapeutic remedies (Table 1). On the basis of our investigations, they are clinically applied for the treatment of fever and parasitic diseases, mouth, skin, respiratory, and urinary tract infections, oral ulcer, and diabetes, in addition to being an adjunctive therapy in cancer and to protecting the liver [1422]. The official record about species in China of genus Tinospora appeared in “Bencao Gangmu Shiyi” [Zhao Xuemin, Qing dynasty, year 1765, Bencao Gangmu Shiyi (本草纲拾遗)]. It is recorded that T. capillipes is primarily used on the therapy of dysentery, diarrhea, and abdominal pain with heat, toxic furuncle ulcer and sore throat. It is also the traditional medicine of Mao, Dong, and Yao minority of China, being applied to the treatment of acute laryngopharyngitis, tonsillitis, gastroenteritis, and bacillary dysentery [23, 24]. Earlier, “Jingzhu Bencao” [Dimaer·Danzeng PengCuo, Qing dynasty, year 1745, Jingzhu Bencao (晶珠)], which is an ancient Chinese Tibetan medicinal encyclopedia, recorded that T. sinensis has been used for relieving rigidity of muscle and activating collaterals (舒筋) and alleviating pain (活血止痛). Its tropism of taste is Xin and Ku and in the liver channel (辛, , 肝经). Chinese Dai Medicine (学) claimed that T. sinensis could also regulate and invigorate the blood (调补气血) and tranquilize the mind (神). It is clinically used to treat palpitation (心) and improve the frail physique (体弱无力). Thailand Lanna Medicine (泰兰纳医学) claimed that T. sinensis was more inclined to clear the heat and cool off the fire (清热火) inside the body, thus usually clinically applied to relieve high fever and ameliorate the symptoms of diabetes [1526]. In India, T. cordifolia referred to as Guduchi (plant which protects from diseases, Sanskrit) has been described in ancient text books of Ayurveda including Sushrut Samhita and Charak Samhita [27]. According to Ayurveda, T. cordifolia itself possesses a bitter, pungent, and astringent taste. The bitter taste is said to improve metabolic activity, even at a cellular level. It is documented to treat gastrointestinal diseases including dyspepsia, flatulence, gastritis, jaundice, diarrhea, splenomegaly, and hemorrhoids. It has a role in the treatment of metabolic disorders such as diabetes and kidney disorders, and it is currently more inclined to be a research focus. It is prescribed for intermittent fevers, infective conditions, urinary disorders, skin diseases, and eye diseases. In combination with other herbs, it is commonly used as an ingredient to treat gout and rheumatoid arthritis. And the well-ground whole plant is applied to fractures. Moreover, T. cordifolia shows healthy effects due to its various nutritious compounds and is considered as a general tonic [27, 28]. The diverse, significant ethnomedicinal properties possessed by this genus could be the basis for further researches to investigate the phytochemical and pharmacological aspects of this genus.

SpeciesPreparation name/formulationMain compositionsMedicinal usesReferences

T. sinensisDecoctionLiquidambar formosana Hance 
Speranskia tuberculata (Bge.) Baill.
Angelica sinensis (Oliv.) Diels 
Clematis chinensis Osbeck 
Bombyx mori Linnaeus 
Cinnamomum cassia Presl 
Achyranthes bidentata Bl.
Spatholobus suberectus Dunn 
Aconitum kusnezoffii Reichb.
Atractylodes lancea (Thunb.) 
Asarum heterotropoides Fr. Schmidt var. mandshuricum (Maxim.) Kitag.
Knee joint osteoarthritis [14]

T. sinensisQutan Tongluo Tang (通络汤)Arca subcrenata Lischke 
Arisaema cum Bile
Drynaria fortune (Kunze) J. Sm.
Dipsacus asper Wall. ex Henry 
Angelica sinensis (Oliv.) Diels 
Chaenomeles speciosa (Sweet) Nakai 
Eucommia ulmoides Oliv.
Paeonia lactiflora Pall.
Corydalis yanhusuo W. T. Wang 
Angelica pubescens Maxim. F. biserrata Shan et Yuan 
Akebia quinata (Thunb.) Decne.
Lumbar disc herniation [15]

T. sinensisHuoxue Shujin Xunxifang (活血舒筋熏洗方)Clematis chinensis Osbeck 
Sparganium stoloniferum Buch.-Ham.
Curcuma phaeocaulis Val.
Uncaria rhynchophylla (Miq.) Miq. ex Havil.
Carthamus tinctorius L.
Salvia miltiorrhiza Bge.
Ligusticum chuanxiong Hort.
Achyranthes bidentata Bl.
Aconitum kusnezoffii Reichb.
Aucklandia lappa Decne.
Ankylosis [16]

T. sinensisSisheng Tang (四生)Rheum palmatum L.
Clematis chinensis Osbeck 
Speranskia tuberculata (Bge.) Baill.
Chaenomeles speciosa (Sweet) Nakai 
Arisaema erubescens (Wall.) Schott 
Aconitum kusnezoffii Reichb.
Aconitum carmichaelii Debx.
Fracture [17]

T. sinensisFumigationLycopodium japonicum Thunb.
Speranskia tuberculata (Bge.) Baill.
Spatholobus suberectus Dunn 
Prunus persica (L.) Batsch 
Carthamus tinctorius L.
Angelica sinensis (Oliv.) Diels  Ligusticum chuanxiong Hort.
Ankle fracture [18]

T. sinensisDecoctionVisceral leishmaniasis [19]

T. capillipesJinguo Heji (金果合)Scrophularia ningpoensis Hensl.
Platycodon grandiflorum (Jacq.) A. DC.
Glycyrrhiza uralensis Fisch.
Ophiopogon japonicas (L.f.) Ker Gawl.
Apis cerana Fabricius

T. capillipesSoaking solutionInfusion phlebitis [21]

T. capillipesPowderUpper respiratory tract infection 
Acute tonsillitis 
Acute gastroenteritis 

T. cordifoliaDecoctionBerberis aristata
Terminalia chebula
Zingiber officinale
Experimental amoebic liver abscess [29]

T. cordifoliaDecoctionPhyllanthus niruri
Terminalia belerica
Terminalia chebula
Phyllanthus emblica
Carbon tetrachloride induced hepatotoxicity [30]

T. cordifoliaDecoctionDiabetic foot ulcers [31]

T. cordifoliaDecoctionAllergic rhinitis [32]

T. cordifoliaDecoctionObstructive jaundice, tuberculosis, sepsis, breast cancer [27]

T. cordifoliaDecoctionBoerhavia diffusa
Berberis aristata
Terminalia chebula
Zingiber officinale
Entamoeba histolytica [33]

T. cordifoliaDecoctionZingiber officinale
Withania somnifera
Tribulus terrestris
Rheumatoid arthritis [34]

3. Pharmacological Activities

Scientific studies all over the world for over 50 years have revealed much insight into the pharmacological functions of Tinospora. Crude extracts and pure compounds from Tinospora plants have shown significant antidiabetic, antioxidant, antitumor, anti-inflammatory, antimicrobial, antiosteoporosis, and immunostimulation properties. In this section, biological activities of the active compounds and mixtures on the species are highlighted.

3.1. Antioxidant Activity

Natural plants used in traditional Chinese medicine have antioxidant effects through different mechanisms, including DPPH radical scavenging assay, superoxide anion scavenging assay, hydroxyl radical scavenging assay, and ABTS radical scavenging method [35]. On a comparative basis, T. sinensis and T. cordifolia were tested to have equal antioxidant activities [36]. Ilaiyaraja and Khanum evaluated the antioxidant potential of different solvent extracts of leaf and stem of T. cordifolia. Scavenging effects on DPPH, ABTS radical, hydroxyl radical, and ferric reducing antioxidant power (FRAP) were found to be highest in methanolic extract of leaf and ethyl acetate extract of stem. It is because the polarity of solvent showed a greater effect on the ordered structure of the active phenolic components [5]. The study on leaf and stem powders of T. cordifolia followed by DPPH method found that the leaf extract powder has higher retention of antioxidant activity than the stem’s [37]. As early as 1998, Cavin et al. isolated and identified three compounds N-cis-feruloyltyramine, N-trans-feruloyltyramine, and secoisolariciresinol from T. crispa. These ingredients proved to be more active than the synthetic antioxidant butylhydroxytoluene (BHT) [38]. Another investigation showed that the essential oil obtained from leaves of T. cordifolia demonstrated strong DPPH radical scavenging activity with IC50 values of μg/mL. The components identified in essential oil include alcohols (32.1%), phenols (16.6%), aldehydes (16.2%), fatty acids (15.7%), alkanes (8.3%), esters (3.2%), terpenes (1.2%), and others (4.8%) [39]. The work carried on hitherto rarely studied fruit of T. cordifolia showed that it is also rich in antioxidant properties with the IC50 being 468 μg/g and EC50 being 1,472 μg/g, yet the effect of the fruit is not comparable to the other parts [5, 6]. These active components and mixtures could serve as valuable indications to develop them as possible antioxidant drugs for the treatment and the prevention of diseases. More importantly, oxidative stress is proved to be critical for the pathogenesis of diabetes mellitus. Clarification of antioxidant issues could help to understand the treatment of diabetes mellitus and promote the development of antidiabetic natural products [40].

3.2. Antidiabetic Activity

Many pharmacologic studies have clearly confirmed the antidiabetic effects of genus Tinospora in vivo. Compared with other commonly seen antidiabetic drugs, T. crispa and T. cordifolia exhibit more powerful antidiabetic activity, and they have been widely used in Asia and Africa as a remedy mainly in regard to type 2 diabetes mellitus [41]. Ruan et al. explored the hypoglycemic effects of borapetoside A mediated through both the insulin-dependent and the insulin-independent pathways. They found that borapetoside A was able to increase the glucose utilization in peripheral tissues, to reduce the hepatic gluconeogenesis, and to activate the insulin signaling pathway. Comparison of the structures of three borapetosides from T. crispa clearly suggested that the C-8 stereochemistry plays a key role in hypoglycemic effect, since the active borapetosides A and C possess 8R-chirality while the inactive borapetoside B possesses 8S-chirality. The location of glycoside at C-3 for borapetoside A (while it is C-6 for borapetoside C) and the formation of lactone between C-4 and C-6 for borapetoside A could account for the different potency in hypoglycemic action for these two compounds [42, 43]. Borapetol B is another antidiabetic active property from T. crispa. By evaluating the blood glucose levels and stimulation of insulin secretion in normoglycemic control Wistar and diabetic Goto-Kakizaki rats, Lokman et al. provided evidence that oral administration of borapetol B has antidiabetic properties mainly due to its stimulation of insulin release [42, 44]. Antidiabetic potential of T. cordifolia stem is also well proven [3, 45, 46]. Patel and Mishra chose sucrose and maltose as substrates to study the enzyme kinetics and the respective Michaelis-Menten constant; meanwhile maximal velocity values were estimated. Three isoquinoline alkaloids from T. cordifolia, namely, jatrorrhizine, palmatine, and magnoflorine, showed IC50 value as sucrase inhibitor to be 36.25, 23.46, and 9.8 μg/mL and maltase inhibitor to be 22.05, 38.42, and 7.60 μg/mL. Furthermore, the increase in plasma glucose level in in vivo studies conducted on rats was significantly suppressed () by all the three alkaloids at 20 mg/kg b.wt. [47]. Kannadhasan and Venkataraman reported that the presence of antioxidant potentials in extract of T. cordifolia was a potent healer in ameliorating diabetes like tissue damage in vivo [48]. It is perfectly consistent with the report that T. cordifolia has a significant () effect in ameliorating the specific parameters toward normal in diabetic animals, and it has a level of efficacy that is considerably good compared to standard drug insulin [49]. These experimental results further enrich previous understanding of the antidiabetic activity of genus Tinospora and provide scientific data of therapeutic efficacy against diabetes mellitus.

3.3. Immunostimulatory Activity

Several Tinospora species have effects on humoral immunity, cellular immunity, and nonspecific immunity. Polysaccharide, a kind of natural macromolecule, has widespread occurrence in biological bodies and has many kinds of biological activities, which plays an important role in regulating immune system [50]. Polysaccharides in Tinospora represent a structurally diverse class of macromolecules and this structural variability can profoundly affect their cell-type specificity and their biological activity in B cells. Previous studies documented that phytogenic polysaccharides could regulate animals’ immune system by combining to membrane receptors of immune cells and initiating the special signaling pathways. This includes stimulating the secretion or proliferation of macrophages, T/B lymphocytes, and natural killer (NK) cells, modulating the release of cytokines, promoting the production of antibodies, and activating the complement system [51]. (1,4)-α-D-Glucan (α-DG) is a novel immune stimulatory drug from T. cordifolia. It exhibited macrophages activating abilities through TLR6 signaling and NF-κB activation mechanism, followed by the production of cytokines and chemokines. It can also differentially modulate cytokine production in the spleen and lung on endotoxaemic juvenile rats. In the lung, α-DG treatment reduced anti-inflammatory cytokine concentrations of IL-1β by 30%, IL-6 by 43%, IFN-γ by 46%, and IL-10 by 31% compared to endotoxaemia. In the spleen, α-DG treatment decreased the ratio of IL-1β to IL-10 by 55% [5254]. Further data showed that α-DG led to significant tachycardia without causing hypotension. Accompanied by significant reduction in the blood hemoglobin and hematocrit concentrations, the effect did not change respiratory variable and/or plasma concentration of inflammatory cytokines in anaesthetized rats [55]. G1-4A, an arabinogalactan polysaccharide from T. cordifolia, is a well-characterized immunomodulatory in both in vitro and in vivo systems. Administration (12.5 mg/kg body weight) of G1-4A to mice led to splenomegaly and an increase in the numbers of T cells, B cells, and macrophages. This increase in spleen cellularity was due to in vivo proliferation of lymphocytes and upregulation of antiapoptotic genes. G1-4A induced proliferation of B cells was completely inhibited by PI3K inhibitor Ly294002, mTOR inhibitor rapamycin, and NF-κB inhibitor plumbagin. Meanwhile, Akt, ERK, and JNK were activated by G1-4A which finally resulted in the activation of IKK, degradation of IκB-α, and translocation of NF-κB to the nucleus [5658]. In the humoral and cell-mediated immune response, T. cordifolia preparation enhanced mean hemagglutination antibody titre and reactive oxygen level against various pathogens [5961]. Polar fractions of T. cordifolia stem at a dose of 40 mg/kg body weight promoted the nonspecific host and defence of the immune system directly acted on peritoneal macrophages [13]. T. crispa crude extract significantly stimulated RAW 264.7 cell viability () and intracellular INF-γ, IL-6, and IL-8 expressions. Study of LC-MS showed that the immunomodulatory active compounds are cordioside, quercetin, eicosenoic acid, and boldine [62]. Other reports indicated that it is the synergistic effect of immunomodulatory active compounds in genus Tinospora that contributed to the immunomodulatory activity [61, 63]. As mentioned above, polysaccharides in genus Tinospora play a key role in the immunostimulatory activity. The characteristics of polysaccharides, which include backbone structure, branching degree, molecular weight, and three spiral structures, affected the activity of immunity. By activating the inherent and acquired immune system to produce antitumor immunity, the immunomodulatory activity could also contribute to the tumor immunotherapy [64].

3.4. Antitumor Activity

Feature chemical components of Tinospora, clerodane diterpenes, showed apparent cytotoxic activity against tumor cells [65]. Nowadays, the antitumor effect of the Tinospora species has been widely studied in vivo and in vitro. The mechanisms of the antitumor activity of Tinospora species are mainly concentrated on the cytotoxicity and cell apoptosis induced. Epoxy clerodane diterpenes were evaluated for the activity against diethylnitrosamine-induced hepatocyte carcinoma; the results concluded that they kick in blocking carcinogen metabolic activation and enhancing carcinogen detoxification [66, 67]. Aqueous ethanolic ingredients of T. cordifolia reduced cell proliferation in dose-dependent manner and induced differentiation in C6 glioma cells. The cell proliferation inhibition was in part mediated through accumulation in S phase and G2/M arrest, with concomitant suppression of p21 expression and inhibition of cyclin-dependent kinase activity [68]. Treatment of hexane extract fraction of T. cordifolia on Ehrlich ascites tumor bearing animals resulted in growth inhibition and induction of apoptosis in a dose-dependent manner in vivo. The mechanism of action was caspase-3 dependent which caused a nuclear localization of apoptosis, meanwhile the formation of apoptotic bodies, nuclear condensation, typical DNA ladder, and decreased cell number and ascites volume [7]. More and Pai observed that treatment with T. cordifolia and LPS of macrophage cell line J774A.1 followed the enhanced NADH-oxidase, NADPH-oxidase, and myeloperoxidase production as compared to medium alone [69]. According to recent studies, alkaloids chemical constituents from plants have the characteristics of better antitumor activity, high effect, good tolerance, and slight side effect [70]. Alkaloid especially palmatine from T. cordifolia significantly decreased tumor size, number and the activity of serum enzyme in DMBA induced skin cancer mice. The alkaloid could also contribute to the reduction of glutathione (GSH), superoxide dismutase (SOD), and catalase; however, it increased DNA damage [71]. The activation of macrophages is another pathway for antitumor activity. (1,4)-α-D-Glucan and G1-4A are immunological active polysaccharides from T. cordifolia. Treatment with G1-4A on a murine lymphoma model increased T cell allostimulatory activity and secretion of IL-12 and TNFα by bone marrow derived dendritic cells, leading to the lysis of target tumor cells in vitro. Polysaccharides can also activate macrophages, NK cells, APDs, and T and B lymphocytes to enhance antitumor immunity concerned with secretion of cytokines, activation of the complement system, induction of apoptosis of tumor cells, and intracellular signal transduction so as to achieve the tumor inhibitory effect by regulations of the immune system [56, 72]. Sonaimuthu et al. identified taxol producing endophytic fungus F. culmorum SVJM072 from medicinal plant of T. cordifolia. Further research showed that the fungal taxol had strong activity against human cancer cell lines by MTT assay and M. tuberculosis H37Rv by Radiometric Bactec 460 assay, which could serve as an excellent alternative source and a genetically engineered species for anticancer compounds [73].

3.5. Anti-Inflammatory and Antimicrobial Activity

Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, and cardiovascular accident. If the process of inflammatory response cannot end normally when cell debris and pathogens were cleared, the biological defence response will become causative factor. Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine [74, 75]. Palmatine and jatrorrhizine, mainly separated from tubers of T. capillipes and T. cordifolia, have widely been applied in clinic owing to their comparatively broad spectrum inhibitory activity. With the EC50 values ranged from 0.0348 to 0.8356 g/L and 0.0240 to 0.8649 g/L, respectively, palmatine and jatrorrhizine exhibited inhibition against many plant pathogens. The two alkaloids vary only in the substituents of position 3 of A ring in terms of the chemical structure. The effectiveness of protoberberine was related to the ammonium N linked at position 7 of aromatic ring in the chemical structure and the inhibitory activity of protoberberine alkaloids altered by the different substituents in A and D rings [76]. The ethanol extract of T. smilacina showed inhibitory activities on COX-1, COX-2, 5-LO, and PA2 with the IC50 values of 63.5, 81.2, 92.1, and 30.5 μg/mL, respectively [9]. Considerable decrease in the levels of iNOS, COX-2, and ICAM-1 resulted in the reduced release of proinflammatory mediators like TNF-α, IL-4, NO, and IgE [10]. An insight into the antimicrobial activity of the ethanolic extracts of T. cordifolia indicated that the secondary metabolites exhibited high inhibitory activity against clinically isolated S. aureus and K. pneumoniae [11]. It is noteworthy that induction of embryogenic callus of T. cordifolia with the presence of additional compounds was able to inhibit both Gram-positive and Gram-negative organisms [77]. All in all, inflammation is a complex and multifaceted problem, so the treatment of inflammation is not a one-dimensional remedy. The anti-inflammation of herbal medicine belonging to genus Tinospora has a favorable applied perspective; with the help of modification in structure it may assist in reaching a multidimensional therapeutic approach to inflammation in the future [78].

3.6. Antiosteoporosis Activity

During recent years, researches in traditional Chinese medicine for the treatment of osteoporosis are increasing, especially in the research and therapeutic application using compound medicine and external medicine, and some progress has been made [79]. T. capillipes and T. cordifolia were reported to induce alkaline phosphatase activity in mesenchymal stem cells based on ecdysone compounds. At the dosage of 25 μg/mL, ethanolic extracts of T. cordifolia stimulated the growth of osteoblasts, increased the differentiation of cells into osteoblastic lineage, and increased the mineralization of bone-like matrix on both the osteoblast model systems. Previously, Gao et al. noted that the stem extracts of T. cordifolia in ovariectomized rats significantly prevented the bone loss in rats induced by ovariectomy without causing proliferative effects in uterus and mammary gland [80, 81]. In addition, the presence of high concentration of calcium in T. cordifolia made it a natural cure for osteoporosis [12]. Moreover, single or synergistic formulations of T. cordifolia with Zingiber officinale have been used in ancient India medicinal system to treat rheumatoid arthritis [34]. However, the morbidity of osteoporosis has been linked to several factors such as age, gender, and races. In order to get a good outcome of osteoporosis treatment, both surgical management and pharmacological treatment are necessary.

3.7. Other Therapeutic Activities

What is more, Tinospora has been investigated to exert other pharmacological activities. Cordifolioside A, mainly isolated in T. cordifolia, has a potential in vivo radioprotective effect and in vitro cytoprotective activity [82]. The impressive radioprotective efficacy may be related to the attenuation of radiation induced decrease of adherence and spreading, increase of IL-1β and GM-CSF levels, and reduction of apoptosis [83]. The radiosensitization by T. cordifolia may be also due to depletion of GSH and GST, accompanied by elevated levels of LPx and DNA damage of tumor cells [84].

Ethanolic extract of T. sinensis exhibited an appreciable activity against promastigotes (IC50  μg/mL) and intracellular amastigotes (IC50  μg/mL). In hamsters, it resulted in % inhibition at 500 mg/kg/day × 5 oral dose levels [1924]. T. cordifolia (100 mg/kg b.wt. for 15 days daily) used in combination with cisplatin in L. donovani infected BALB/c mice selectively induced Th1 type of immune response. It was concluded by the enhanced levels of IFN-c and IL-2 with moderate decline of Th2 specific cytokines IL-4 and IL-10 [85].

The least polar alkaloid from T. crispa, columbamine, showed strong acetyl-cholinesterase inhibitory activity with IC50 48.10 μmol/L. The structure-activity relationships derived from these results suggested that the quaternary nitrogen in the skeleton has some effect but that a high degree of methoxylation is more important for acetylcholinesterase inhibition [86].

T. cordifolia ethanol extract exhibited significant neuroprotection by increasing the dopamine levels ( and 2.45 ± 0.40 ng/mg of protein) and complex I activity (77.14 ± 0.89 and 78.50 ± 0.96 nmol/min/mg of protein) at 200 and 400 mg/kg, respectively [87]. Combination of ethanolic extracts of T. cordifolia, B. monnieri, and E. alsinoides in equal proportion provided synergistic nootropic effect on scopolamine induced amnesia in rats [88].

4. Chemical Constituents

The chemical constituents of Tinospora have long been the pursued objectives of the researchers, and multiple classes of chemical constituents have been isolated and reported. Within these compounds, diterpenoids are the most dominant constituent found in the currently studied species in this genus. Up to now, 223 compounds have been isolated from genus Tinospora, including terpenoids, alkaloids, steroids, C6-C3 derivatives, and polysaccharides as well as other components. The compounds list and their structures are shown in Table 2 and Figure 1.

NumberCompoundsSpecies (part of plant)References

1Tinocapillins CT. capillipes (R)[123]
2Tinocallone AT. capillipes (R)[107]
3Tinocallone BT. capillipes (R)[107]
4TinocordinT. cordifolia[124]
5Tinocapillins AT. capillipes (R)[123]
6Fibaruretin HT. sagittata (R)[125]
7Tinocapillins BT. capillipes (R)[123]
8Fibaruretin GT. sagittata (R)[125]
9SagitoneT. sagittata var. yunnanensis (R)[93]
10TinospononeT. cordifolia (S)[113]
11TinosporasideT. cordifolia (S)[100, 113]
12Tinosporaside tetraacetateT. cordifolia (S)[113]
13Amritoside DT. cordifolia (S)[109]
14TinocordiosideT. cordifolia (S)[109]
15Tinocordioside tetraacetateT. cordifolia (S)[109]
16Boropetol BT. crispa (S)[126]
17TinocrisposideT. crispa (S)[127]
18Boropetoside FT. tuberculata (S)[128]
19(2R,5R,6S,9S,10S,12S)-15,16-Epoxy-2-hydroxy-6-O-(β-D-glucopyranosyl)-cleroda-3,7,13(16),14-tetraen-17,12-olid-18-oic acid methyl esterT. crispa[114]
20(5R,6S,9S,10S,12S)-15,16-Epoxy-2-oxo-6-O-(β-D-glucopyranosyl)-cleroda-3,7,13(16),14-tetraen-17,12-olid-18-oic acid methyl esterT. crispa[91]
21(5R,6R,8S,9R,10S,12S)-15,16-Epoxy-2-oxo-6-O-(β-D-glucopyranosyl)-cleroda-3,13(16),14-trien-17,12-olid-18-oic acid methyl esterT. crispa[91]
22(2R,5R,6R,8S,9S,10S,12S)-15,16-Epoxy-2-hydroxy-6-O-β-D-glucopyranosyl-(1→6)-α-D-xylopyranosyl-cleroda-3,13(),14-trien-17,12-olid-18-oic acid methyl esterT. crispa[91]
23(2R,5R,6R,8R,9S,10S,12S)-15,16-Epoxy-2-hydroxy-6-O-(β-D-glucopyranosyl)-cleroda-3,13(16),14-trien-17,12-olid-18-oic acid methyl esterT. crispa[91]
24(5R,6R,8S,9R,10R,12S)-15,16-Epoxy-2-oxo-6-O-(β-D-glucopyranosyl)-cleroda-3,13(16),14-trien-17,12-olid-18-oic acid methyl esterT. crispa[91]
25Borapetoside BT. crispa[38, 91]
26Borapetoside CT. crispa[38, 91]
27TinophyllolosideT. sagittata var. yunnanensis (R)[92]
28EpitinophyllolosideT. sagittata var. yunnanensis (R) 
T. capillipes (R)
29Tinoscorside CT. cordifolia[94]
30Borapetoside FT. cordifolia[94]
31Borapetoside BT. cordifolia[94]
32Tinocrispol AT. crispa (S)[129]
33Amritoside CT. cordifolia (S)[109]
342-O-Lactoylborapetoside BT. crispa (S)[129]
356′-O-Lactoylborapetoside BT. crispa (S)[129]
36Borapetoside HT. tuberculata (S)[95]
37Octa-O-acetylborapetoside HT. tuberculata (S)[95]
38Borapetoside HT. crispa (S)[96]
39Tinospinoside CT. sagittata var. yunnanensis (R)[97]
40Tinospinoside AT. sagittata (Oliv.)Gagnep.(R)[98]
41Tinospinoside BT. sagittata (Oliv.)Gagnep.(R)[98]
42Rumphioside AT. rumphii (S)[117]
43Rumphioside BT. rumphii (S)[117]
44Rumphioside CT. rumphii (S)[117]
45Rumphioside DT. rumphii (S)[117]
46Furanoid diterpene glycosideT. cordifolia (S)[130]
47CordiosideT. cordifolia (S)[99]
48Cordioside tetraacetateT. cordifolia (S)[99]
49Cordifoliside DT. cordifolia (S)[100]
50Cordifoliside ET. cordifolia (S)[100]
51Boropetoside GT. tuberculata (S)[128]
52MalabarolideT. malabarica (S)[131]
53Tinosposinenside AT. sinensis (S)[101]
54Tinosposinenside BT. sinensis (S)[101]
55Tinosposinenside CT. sinensis (S)[101]
561-Deacetyltinosposide AT. sinensis (S)[103]
57Tinosineside AT. sinensis (S)[103, 104]
58Tinosineside BT. sinensis (S)[104]
59Penta-O-acetyl-tinosineside AT. sinensis (S)[104]
60Hexa-O-acetyl-tinosineside AT. sinensis (S)[104]
61(3R,4R,5R,6S,8R,9S,10S,12S)-15,16-Epoxy-3,4-epoxy-6-O-(β-D-glucopyranosyl)-cleroda-3,13(16),14-trien-17,12-olid-18-oic acid methyl esterT. crispa[91]
62Tinospinoside DT. sagittata (R)[105, 132]
63TinosporideT. cordifolia (S)[113]
64Furanolactone clerodane diterpeneT. cordifolia (S)[113]
65Furanolactone clerodane diterpeneT. cordifolia (S)[113]
66TinosporicideT. malabarica (S)[113]
67JateorinT. smilacina (S)[114]
68Palmatoside FT. smilacina (S)[114]
69(5R,10R)-4R,8R-Dihydroxy-2S,3R:15,16-diepoxycleroda-13(16),17,12S,18,1S-dilactoneT. cordifolia (S)[110]
70MenispermacideT. malabarica (S)[127]
71TinosporasideT. cordifolia (S)[113]
72Ioa-hydroxy columbinT. malabarica (S)[131]
73TinosideT. capillipes (Rh)[107]
74IsocolumbinT. capillipes (Rh)[107]
75ColumbinT. craveniana (R) 
T. sagittata var. yunnanensis (R) 
T. capillipes (R)
[92, 93, 106, 107, 132, 133]
76Palmatoside CT. sagittata var. yunnanensis (R) 
T. capillipes (R)
[93, 107, 115]
77FibleucinT. sagittata var. yunnanensis (R) 
T. capillipes (R)
78IsocolumbinT. capillipes (R) 
T. sagittata (R) 
T. craveniana (R)
[92, 106, 107, 133]
79TinosideT. sagittata (R) 
T. capillipes (R)
806-Hydroxy columbinT. sagittata (R)[92]
81(1R,4S,5R,8S,9R,10S,12S)-15,16-Epoxy-4-O-(β-D-glucopyranosyl)-cleroda-2,13(16),14-triene-17(12),18(1)-diolideT. crispa[91]
82Tinospinoside ET. sagittata var. yunnanensis (R)[98]
838-Hydroxy columbinT. cordifolia[116, 128]
84Tinospin ET. sagittata (R)[105, 112]
85Cordifolide BT. cordifolia (S)[108]
86Cordifolide CT. cordifolia (S)[108]
87Furanolactone diterpeneT. cordifolia (S)[113]
88Boropetol AT. crispa (S)[134]
89Boropetoside AT. crispa (S)[134]
90Cordifolide AT. cordifolia (S)[108]
91MenispermacideT. smilacina (S)[114]
92Borapetoside AT. crispa[91]
93TinosporaclerodanoidT. cordifolia (S)[102]
94Tinotufolin AT. tuberculata (L)[116, 128]
95Tinotufolin BT. tuberculata (L)[116, 128]
96Amritoside BT. cordifolia (S)[109]
97Tinotufolin CT. crispa (S)[96]
98Methyl(1α,4αa,5α,6β,8aα)-5-2-(3-furan-3-ene-2-one)ethyl-1,2,3,4,4a,5,6,7,8,8a-decahydro-1,2-dihydroxy-1-naphthalenecarboxylateT. rumphii (L)[115]
99Tinotufolin FT. crispa (S)[96]
100Tinotufolin ET. crispa (S)[96]
101Sagittatayunnanoside BT. sagittata var. yunnanensis (R)[97]
102Sagittatayunnanoside AT. sagittata var. yunnanensis (R)[97]
103Sagittatayunnanoside CT. sagittata var. yunnanensis (R)[97]
104Sagittatayunnanoside DT. sagittata var. yunnanensis (R)[97]
105Amritoside AT. cordifolia (S)[109]
106Tinosagittone AT. sagittata (R)[92]
107Tinosagittone BT. sagittata (R)[92]
108Tinocapilactone AT. capillipes[107]
109Tinocapilactone BT. capillipes[107]
110TinosporafuranolT. cordifolia (S)[102]
111TinosporaclerodanolT. cordifolia (S)[102]
112TinosporafurandiolT. cordifolia (S)[100]
113(2aβ,3α,5aβ,6β,7α,8aα)-6-2-(3-Furanyl)ethyl-2a,3,4,5,5a,6,7,8,8a,8b-decahydro-2a,3-dihydroxy-6,7,8b-trimethyl-2H-naphtho1,8-bcfuran-2-oneT. rumphii (L)[104115]
114Boropetoside DT. tuberculata (S)[116, 128]
115Boropetoside ET. tuberculata (S)[116, 128]
116Tinotufolin DT. crispa (S)[96]
117Borapetoside ET. rumphii (S)[118]
118Rumphioside IT. rumphii (S)[118]
119Rumphioside FT. rumphii (S)[117]
120Rumphioside ET. rumphii (S)[117]
121(2R,7S,8S)-8-[(2S)-2-(3,4-Dihydroxy-2,5-dimethoxytetrahydro-3-furanyl)-2-hydroxyethyl]-2,8-dimethyl-10-oxo-11-oxatricyclo[,7]dodec-3-ene-3-carboxylateT. crispa[91]
122Borapetoside DT. crispa[91]
123Baenzigeride BT. baenzigeri (S)[120]
124Baenzigeroside BT. baenzigeri (S)[120]
125Baenzigeride AT. baezigeri (S)[120]
126Baenzigeroside AT. baezigeri (S)[120]
127CycloeuphordenolT. malabarica (S)[113]
128CycloeucalenolT. crispa (S)[120]
129CycloeucalenoneT. crispa (S)[120]
130TinosinensideT. sinensis (S)[101]
13111-HydroxymustakoneT. capillipes[61, 121, 135]
132TinocordisideT. capillipes[61, 121, 135]
133TinocordifoliosideT. sinensis (S) 
T. cordifolia (S)
[103, 122, 136]
134TinocordifolinT. cordifolia (S)[136]
135Tinocordifolioside tetraacetateT. cordifolia (S)[136]
136Angelicoidenol-2-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranosideT. cordifolia[94]

137BerberineT. cordifolia (S)[113]
138PalmatineT. cordifolia (S) 
T. malabarica (S)
[127, 137]
139JatrorrhizineT. cordifolia (S)  
T. capillipes (R)
[137, 138]
14013-HydroxycolumbamineT. sagittata (R) 
T. capillipes (R)
[14, 139]
14113-HydroxyjatrorrhizineT. sagittata (R) 
T. capillipes (R)
[14, 139]
142DemethyleneberberineT. sagittata (R) 
T. capillipes (R)
[14, 139]
14313-HydroxypalmatineT. sagittata (R) 
T. capillipes (R)
[14, 139]
144ColumbamineT. sagittata (R) 
T. capillipes (R)
[14, 139]
145JatrorrhizineT. sagittata (R) 
T. capillipes (R) 
T. sinensis (S)
[14, 106, 139, 140]
146IsocolumbamineT. hainanensis (S) 
T. capillipes (R) 
T. sagittata (R)
147StepharanineT. sagittata (R) 
T. capillipes (R)
[14, 139]
148DehydrodiscretamineT. sagittata (R) 
T. capillipes (R)
[14, 139]
149DehydrocorydalmineT. sagittata (R) 
T. capillipes (R)
[14, 106, 139]
150PalmaturbineT. sinensis
T. craveniana (R)
[14, 133, 139, 140]
151PalmatineT. sinensis (S) 
T. capillipes (R) 
T. craveniana (R)
[103, 106, 133, 140]
152S-trans-N-MethyltetrahydrocolumbamineT. hainanensis (S)[141]
153S-trans-CyclanolineT. hainanensis (S)[141]
1543-Hydroxy-2,9,11-trimethoxy-5,6-dihydro-isoquino3,2-a-isoquinolinyliumT. sinensis[140]
1554,13-Dihydroxy-2,8,9-trimethoxydibenzo [a,g] quinoliziniumT. crispa[86]
156BerberineT. smilacina (S)[92]
157MagnoflorineT. cordifolia (S) 
T. malabarica (S) 
T. capillipes (R)
[113, 138]
158Menisperine  T. capillipes (R) 
T. cordifolia (S)
[113, 138]
159N-Formyl anonaineT. crispa (S) 
T. malabarica (S)
160N-Formyl nornuciferineT. crispa (S)[113]
161N-Acetyl nornuciferineT. crispa (S)[38]
162N-Formylasimilobine-2-O-β-D-glucopyranosideT. crispa (S)[96]
163N-FormylannonainT. capillipes[61, 135]
164MagnoflorineT. sagittata (R) 
T. capillipes (R)
[14, 106, 139]
165MenisperineT. sagittata (R) 
T. capillipes (R)
[14, 139]
166TembetarineT. sagittata (R) 
T. capillipes (R)
[14, 139]
167ReticulineT. sagittata (R) 
T. capillipes (R)
[14, 139]
168TembetarineT. cordifolia (S)[113]
169HigenamineT. crispa[142]
170AdenineT. crispa[142]
171AdenosineT. crispa[143]
172UridineT. crispa[142]
173SalsolinolT. crispa[142]
174(−)-LitcubinineT. crispa[142]
175TyramineT. crispa[142]
176N-trans-Feruloyl tyramineT. tuberdata (S)[38]
177N-cis-Feruloyl tyramineT. tuberculata (S)[3638]
178N-trans-Feruloyl tyramine diacetateT. cordifolia (S)[38, 136]
179KokusaginineT. malabarica (S)[113]
180N-Methyl-2-pyrrolidoneT. capillipes[61, 135]
181CholineT. cordifolia (S)[137]
1822,3-Dihydroxy-N-(2S,3S,4R)-1,3,4-trihydroxyicosan-2-yltetracosanamideT. oblongifolia[144]

183TinosporinoneT. malabarica (HW)[113]
1845-Alloxy-6,7,4′-trimethyl flavoneT. malabarica (HW)[113]
185KaempferolT. malabarica (S)[113]
186AstragalinT. malabarica (S)[113]
187QuercitrosideT. malabarica (S)[113]
188(−)-EpicatechinT. cordifolia (S)[145]
189EcoisolariciresinolT. crispa[38]
190Secoisolariciresinol-9′-O-β-D-glucopyranosideT. capillipes[38, 94]
191Sagitiside AT. sagittata var. yunnanensis (R)[105, 112]
192(+)-Lyoniresinol-2α-O-β-D-glucopyranosideT. sagittata var. yunnanensis (R)[105, 112]
193(+)-5′-Methoxyisolariciresinol-3α-O-β-D-glucopyranosideT. sagittata var. yunnanensis (R)[105, 112]
1943(a,4-dihydroxy-3-methoxybenzyl)-4-(4-hydroxy-3-methoxybenzyl) tetrahydrofuranT. cordifolia (S)[113]
195Lirioresino-β-dimethyl etherT. sinensis[140]
196Pinoresinol-di-O-glucosideT. capillipes[94]
197(−)-Pinoresinol-4-O-β-D-glucopyranosideT. sinensis (S)[103]
1988′-EpitanegoolT. sinensis (S)[103]
199SyringinT. crispa[142]
200Tinoscorside DT. capillipes[94]
201Cordifolioside AT. capillipes[38, 61, 135]
202Docosyl-3,4-dihydroxy-trans-cinnamateT. oblongifolia[144]
2032-(40-Hydroxyphenyl)-ethyl lignocerateT. oblongifolia[144]
204TinotuberideT. crispa (S)[113]
205Isoorientin 2′′-O-(E)-sinapateT. crispa (L)[146]
2062′′-(E)-p-coumarateT. crispa (L)[146]
207Cosmosiin 6′′-(E)-ferulateT. crispa (L)[146]
208Cosmosiin 6′′-(E)-cinnamateT. crispa (L)[146]

209β-SitosterolT. oblongifolia[144]
210β-Sitosterol glycosideT. oblongifolia[144]
211β-SitosterolT. cordifolia (S) 
T. sinensis (S) 
T. craveniana (R)
[102, 140]
2122-Deoxy crustecdysoneT. capillipes (R)[113]
2132-Deoxy-3-epicrustecdysoneT. capillipes (R)[113]
2142-Deoxy-3-epicrustecdysone-3-O-D-glucopyranosideT. capillipes (R)[113]
21520α-Hydroxy ecdysoneT. cordifolia (S)[113]
21620β-Hydroxy-ecdysone-2-O-β-glucopyranosideT. craveniana (R)[147]
21720β-HydroxyecdysoneT. sagittata (R) 
T. capillipes (R) 
T. craveniana (R)
[14, 106, 133, 139]
2182-Deoxy-20β-hydroxyecdysoneT. sagittata (R) 
T. capillipes (R)
[14, 106, 139]
2192-Deoxy-3-epi-20β-hydroxyecdysoneT. sagittata (R) 
T. capillipes (R)
[14, 139]
2202-Deoxy-20β-hydroxyecdysone-3-O-glucopyranosideT. sagittata (R) 
T. capillipes (R)
[14, 106, 139]
221Polypodine B 20,22-acetonideT. cordifolia[94]
222Makisterone AT. hainanensis (S)[148]
22324-Epi-makisterone AT. hainanensis (S)[148]

4.1. Terpenoids
4.1.1. Diterpenes

Diterpenoids with clerodane-type skeleton represent the second most prevalent chemical class of the genus with over one hundred. They are the characteristic-hot constituents containing 20-C atom forming a 6/6 bicyclic skeleton. According to different stereochemistry of the decalin ring junction, this type of structure is grouped into neo-clerodane, ent-clerodane, and nor-neo-clerodane. The skeleton of neo-clerodane and ent-clerodane-type diterpene is the same, with some differences in the configuration. The spatial locations of angular methyl group linked at C-5, C-8, and C-9 are differed. Specifically, it is C-5(S), C-8(R), and C-9(S) for neo-clerodane and C-5(R), C-8(S), and C-9(R) for ent-clerodane. Nor-neo-clerodane is an oxidation product of neo-clerodane, and one more five-membered unsaturated lactone ring is added compared with neo-clerodane [89]. We prefer to divide the diterpenoids into another two major types. A naphthalene ring fused to a lactone ring forms the main basic structure of the diterpenoids. The C-9 position often has a six-membered side chain and usually forms a furan-ring moiety. Lactone ring commonly exists in this type of compounds. Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings with the similar arrangement of phenanthrene. Meanwhile, those ones without a lactone ring linked at C-8 and C-12 account for another small part of terpenoids. Apart from what is mentioned above, the few ones with isomerization in ring C then are in another group.

(1) Diterpenes with Type 1 Skeleton. Compounds with type 1 skeleton are abundant in this genus. Due to the decalin core motif, Diels-Alder cycloaddition proved to be a valuable tool in their construction [90]. However, different synthetic routes result in the different positions of double bond and distinct substituents of the parallelized 6/6 bicyclic skeleton. These compounds are mostly reported from T. cordifolia, T. crispa, and T. sagittata, while other plant species possess a few. Compounds 160 are typical clerodane-type diterpenes characterized by the presence of one or more double bond or methyl metabolites attached to the clerodane core [91105]. Compounds 6186 have distinct connecting mode of lactone ring linked at C-1/C-18 with different spatial configurations of substituent groups [9193, 106112]. Compounds 8792, as a tiny type, caused more attention to be paid to the ethane thiolate group [101, 108, 113, 114]. Tinosporaclerodanoid (93) is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol, never isolated from a natural or synthetic source before. Location of the carbonyl group is determined to be at C-1 [102].

(2) Diterpenes with Type 2 Skeleton. This is another type of clerodane diterpene without the C-8/C-12 linking lactone ring, yielding a variant genre of diterpenes featured by the decalin ring junction of different stereochemistry. In these compounds, the C-8 position always contains a methyl or methoxycarbonyl group, which obstructs the formation of the lactone bridge between C-8 and C-12; see compounds 94 to 112. They are mainly identified from T. cordifolia, T. tuberculate, T. sagittata var. yunnanensis, and T. sagittata. There is an ester bond connected between C-1 and C-4 (106108). One more sugar glucose unit in sagittatayunnanoside C (103) indicates that it may be the derivative of sagittatayunnanoside A (102) via the glycosylation of hydroxyl at C-18 [97, 115].

(3) Diterpenes with Other Structures. Compounds 113116 are structurally similar, and the differences between the basic structures are the oxidation degree of ring A. The diversity among their lactone ring may be an influencing factor causing these compounds to exhibit varying degrees of biological activities against the same cancer cell line [96, 115, 116]. Compounds 117120 were isolated from the stem of T. rumphii, and the lactone ring linking between C-6 and C-8 is quite remarkable [117, 118]. Compounds 121-122 from T. crispa have the same nucleus structure as compound 117’s. Compounds 123126 are rearranged clerodane diterpene, obtained from the stems of T. baenzigeri, of which baenzigeride (123) and baenzigeroside (124), as the novel skeleton, arising from the cis-ent-neo-clerodane epoxide are considered to be the precursor of compounds 125 and 126 [119].

4.1.2. Other Terpenes

There are ten compounds in this category, involving three triterpenoids (127129), six sesquiterpenoids (130135), and one monoterpenoid (136). Cycloeuphordenol is a novel 31-nortriterpene in T. malabarica. The other two new triterpenes are cycloeucalenol and cycloeucalenone producing mild cardiotonic effects [120]. A new rearranged cadinane sesquiterpene glycoside, tinosinenside, is tested to have inhibitory activities against R-glucosidase [101]. Tinocordiside, consisting of a tricyclic skeleton with a cyclobutane ring, is found in the aqueous fraction of T. cordifolia [61, 121]. Compounds 133135 possessing the core structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]. Compound 136 is the only monoterpenoid isolated from the methanol extract of T. cordifolia [94].

4.2. Alkaloids
4.2.1. Berberine Alkaloids

Twenty berberine alkaloids from genus Tinospora have been reported (137156). Commonly, the exact positions of methoxy groups are linked at C-2, C-3, C-9, and C-10. Rings C and D are coplanar with each other and in good conjugation, yet rings A and B are not in the same plane because of the saturated carbons at C-5 and C-6. If the methyl linked at C-2 or C-3 is lost, it cannot be well stabilized by the vicinal unsaturated ring C. When the methyl is lost from C-9, a stable intermediate could be formed. After the loss of two H atoms at C-5 and C-6 (rings A and B are in a plane at this time), the two methoxy groups at C-2 and C-3 can also turn into a methylenedioxy group [139]. The polarity of the overall compound interrelates with the inhibitory of cholinesterases [86].

4.2.2. Aporphine Alkaloids

Nine (157165) aporphine alkaloids are isolated and characterized in this genus. When the hydroxyl is at C-1, it seems more favorable that the H2O-group tends to be lost in successive fragmentation. Possessing two pairs of vicinal hydroxyl and methoxy groups (usually between C-1 and C-2 and C-10 and C-11), two molecules of methanol moieties tend to be lost consecutively. In mass spectrometry, the losses of methyls and the second molecule of methanol may as well be considered to be minor fragmentation. Such changes may be related to the steric interactions between the hydroxyl at C-1 and the epoxy group at C-10 and C-11. Meanwhile, the stable aromatic ring prevents diversifications in the core structure [139].

4.2.3. Other Alkaloids

Compounds 166169 are benzylisoquinoline alkaloids which play a significant role as a minute part. Compounds 170174 from T. crispa acted in concert on the cardiovascular system of anesthetized rats [142, 143]. Compounds 175178 are homologous provided with identical basic skeleton [149, 150].

4.3. C6-C3 and C6-C3-C6 Constituents

Other components isolated from the genus include six flavonoids, ten lignans, and several others [94, 103, 140]. Compounds 183188 belonging to flavonoid are the antioxidant profile of genus Tinospora. It is noteworthy that (−) epicatechin was reported for the first time in the stem extract of T. cordifolia [145]. Compounds 189198 are lignan in which 192194 were tested having obvious antioxidant activity [112]. Syringin (199) isolated from the crude butanol extract of T. crispa acted in concert with other active ingredients on the cardiovascular system [142]. Tinoscorside D (200) was isolated and elucidated based on spectroscopic data from the methanol extract of T. cordifolia aerial parts [94].

4.4. Steroids

Tinospora plants also contain steroids that are usually encountered in natural sources, and those presented in genus Tinospora are mostly derivatives of β-sitosterol. Up to now, fifteen of this kind of ingredients have been isolated and identified. Among them, β-sitosterol and β-sitosteryl glucoside were frequently found in Tinospora species [110, 113, 139, 144].

4.5. Polysaccharides

In the last decades polysaccharides from genus Tinospora have caught a great deal of attention due to their broad spectrum of therapeutic properties and relatively low toxicity, particularly being immune-enhancing agents. The composition of polysaccharides from T. cordifolia was reported as follows: glucose 98.0%, arabinose 0.5%, xylose 0.8%, galactose 0.3%, rhamnose 0.2%, and mannose 0.2% [151, 152]. Through subjecting to GC-MS analysis, the types of monosaccharides’ linkages were investigated to be terminal-glucose, 4-xylose, 4-glucose, 4,6-glucose, and 2,3,4,6-glucose [153]. Sharma et al. reported that the active polysaccharide fractions mainly constitute glucose, fructose, and arabinose as monomer units. The polymorphonuclear leukocyte function test concluded that they were responsible for immune enhancement [135]. Administration of the polysaccharide fraction from T. cordifolia with tumor challenge inhibited (72.0%) the metastases formation in the lungs of syngeneic C57BL/6 mice [154]. Bioassay guided fractionation and separation of the ethanolic extract of T. crispa leaf led to four acylated glycosylflavonoids. Among the isolated compounds, isovitexin 2′′-(E)-p-coumarate (206) showed the best activity against α-glucosidase with an IC50 value of μM [146].

5. Metabolism and Pharmacokinetics

To date, there are few pharmacokinetics studies of the extracts of this genus. Previous pharmacokinetics studies of Tinospora mainly focused on its diterpenes and its derived compounds that fitted to a one-compartment model. Shi et al. reported that columbin (75) and its derivatives (72, 74, 80, and 83) are commonly present in the root of T. capillipes and T. sagittata. Columbin is the major urinary metabolites in rats to which these compounds were orally given. These components could be absorbed and metabolized by the gastrointestinal tract. But pharmacokinetic studies showed that absorption of diterpene components was poorly absorbed through the gastrointestinal tract and they were quickly eliminated. Owing to the similar structures, these compounds have parallel pharmacokinetic parameters in vivo. Columbin is eliminated with systemic clearance of  L/h/kg after i.v. administration demonstrating a little higher blood flow rate (3.3 L/h/kg in rats) than the hepar. It could be concluded that columbin was rapidly cleared via hepatic clearance and extrahepatic clearance. The volume of distribution at terminal phase was  L/kg demonstrating a much higher total body water of 0.67 L/kg. The above researches suggested that columbin has extensive distribution into extravascular systems. Because columbin is almost insoluble in water, the absolute oral bioavailability of columbin is only %. The time to reach the maximum plasma drug concentration is less than 5 mins. The aforementioned indicate that the absorption of columbin is limited and quickly eliminated [107, 155, 156]. So it is necessary to improve its absorption in vivo for clinical application in further research on pharmaceutical preparation. Since few pharmacokinetics studies of the extracts of Tinospora species have been reported, the needs for mechanism of actions on them are necessary in view of the wide bioactivities and extensive uses, and metabolism and pharmacokinetics studies are warranted to find out its most perspective activities.

6. Safety Evaluation

The clinical existence for herbs of genus Tinospora over centuries are in a way themselves evidences of therapeutic utility. No adverse effects have been reported in this genus prescribed under reasonable doses application. T. cordifolia is advocated as a tonic in infants and children to facilitate growth. The LD50 value for T. cordifolia is higher than 1 g/kg for oral administration [157]. Acute toxicity study with the dose of 3 g/kg demonstrated that T. cordifolia does not have any side effects and reported no death of the experimental rats [158]. When administered in doses of 0.1 g/kg for 12 weeks, T. cordifolia does not trigger any unfavorable factors on liver and renal function parameters in rats. It precipitated the increment of leukocytosis with neutrophilia in rats while no such effect was observed in healthy humans [27, 159]. T. cordifolia treatment does not display clastogenicity and DNA damaging effect in bone marrow erythrocytes and peripheral blood lymphocytes [160]. And no neurological impairment or marked central nervous system depressant activities were shown [161]. Administration of T. cordifolia to healthy volunteers has been found to be safe in phase I study, and the drug was well tolerated [157, 162]. It has also been shown not to exert any conspicuous adverse reactions on the gastrointestinal system, renal system, cardiovascular system, and central nervous system [163]. However, systematic toxicological tests and safety evaluations have not been carried out extensively within the Tinospora species. Generally speaking, it could be used safely at low and middle dosage. Since test for toxicology of chemical constituents in this genus are rare until now, more toxicity researches remain to be done.

7. Conclusions

The review paper summarized a total of 223 compounds and abundant clerodane-type diterpene components that were reported from the genus Tinospora, with 152 references cited. We noted that Tinospora has an extensive distribution, targeted clinical application, and diverse biological and pharmacological activities of pure compounds and extracts. Previous phytochemical researches on the genus revealed the extensive presence of terpenoid, alkaloid, C6-C3 derivative, polysaccharide, and other compound types. The pharmacological activities were mainly regarded on antidiabetic, antioxidant, antitumor, anti-inflammatory, antimicrobial, antiosteoporosis, and immunostimulation activities. From the review, it can be seen that phytochemical investigations, pharmacological researches, and traditional clinical application mainly focus on 4 Tinospora species, T. sagittata, T. capillipes, T. cordifolia, and T. crispa. The related chemical and biological activities toward other Tinospora species are still blank. So, plenty of further studies are necessary in order to illustrate the chemodiversity and to make full use of the biological significance of the compounds and extracts of Tinospora, especially the antidiabetic and antioxidant activities. Future works will be focused on the following aspects: to use Tinospora species as chemopreventive and therapeutic agent for various diseases, or to use them as adjuncts to exiting drugs to the treatment of diabetes, or to discover important and interesting biologically active compounds from these herbs by bioactivity-guided isolation. The authors wish the review can provide valuable data for explorations and advanced researches of Tinospora species.

Competing Interests

The authors confirm that this paper’s content has no conflict of interests.


The authors would also like to express their gratitude to Beijing University of Chinese Medicine for financial support of this paper.


  1. P. A. Shah and G. B. Shah, “Preliminary screening of Tinospora cordifolia extracts and guduchi satva for anti-rheumatoid activity,” International Journal for Pharmaceutical Research Scholars, vol. 5, no. 2, pp. 7–13, 2016. View at: Google Scholar
  2. Committee for the Pharmacopoeia of PR China, Pharmacopoeia of PR China, Part I, China Medical Science and Technology Press, Beijing, China, 2015.
  3. R. Sharma, H. Amin, Galib, and P. K. Prajapati, “Antidiabetic claims of Tinospora cordifolia (Willd.) Miers: critical appraisal and role in therapy,” Asian Pacific Journal of Tropical Biomedicine, vol. 5, no. 1, pp. 68–78, 2015. View at: Publisher Site | Google Scholar
  4. J. Z. Yuan, Studies on the Constituents of Smilax glabra Roxb. and Tinospora sinensis (Lour.) Merr, Shenyang Pharmaceutical University, Shenyang, China, 2004.
  5. N. Ilaiyaraja and F. Khanum, “Antioxidant potential of Tinospora cordifolia extracts and their protective effect on oxidation of biomolecules,” Pharmacognosy Journal, vol. 3, no. 20, pp. 56–62, 2011. View at: Publisher Site | Google Scholar
  6. M. I. Khan, P. S. C. S. Harsha, P. Giridhar, and G. A. Ravishankar, “Pigment identification, antioxidant activity, and nutrient composition of Tinospora cordifolia (willd.) Miers ex Hook. f & Thoms fruit,” International Journal of Food Sciences and Nutrition, vol. 62, no. 3, pp. 239–249, 2011. View at: Publisher Site | Google Scholar
  7. G. Thippeswamy and B. P. Salimath, “Induction of caspase-3 activated DNase mediated apoptosis by hexane fraction of Tinospora cordifolia in EAT cells,” Environmental Toxicology and Pharmacology, vol. 23, no. 2, pp. 212–220, 2007. View at: Publisher Site | Google Scholar
  8. P. Kapur, B. M. J. Pereira, W. Wuttke, and H. Jarry, “Androgenic action of Tinospora cordifolia ethanolic extract in prostate cancer cell line LNCaP,” Phytomedicine, vol. 16, no. 6-7, pp. 679–682, 2009. View at: Publisher Site | Google Scholar
  9. R. W. Li, D. N. Leach, S. P. Myers et al., “Anti-inflammatory activity, cytotoxicity and active compounds of Tinospora smilacina Benth,” Phytotherapy Research, vol. 18, no. 1, pp. 78–83, 2004. View at: Publisher Site | Google Scholar
  10. M. Tiwari, U. N. Dwivedi, and P. Kakkar, “Tinospora cordifolia extract modulates COX-2, iNOS, ICAM-1, pro-inflammatory cytokines and redox status in murine model of asthma,” Journal of Ethnopharmacology, vol. 153, no. 2, pp. 326–337, 2014. View at: Publisher Site | Google Scholar
  11. F. Bonvicini, M. Mandrone, F. Antognoni, F. Poli, and G. A. Gentilomi, “Ethanolic extracts of Tinospora cordifolia and Alstonia scholaris show antimicrobial activity towards clinical isolates of methicillin-resistant and carbapenemase-producing bacteria,” Natural Product Research, vol. 28, no. 18, pp. 1438–1445, 2014. View at: Publisher Site | Google Scholar
  12. R. Gowrishankar, M. Kumar, V. Menon et al., “Trace element studies on Tinospora cordifolia (Menispermaceae), Ocimum sanctum (Lamiaceae), Moringa oleifera (Moringaceae), and Phyllanthus niruri (Euphorbiaceae) using PIXE,” Biological Trace Element Research, vol. 133, no. 3, pp. 357–363, 2010. View at: Publisher Site | Google Scholar
  13. M. Sengupta, G. D. Sharma, and B. Chakraborty, “Effect of aqueous extract of Tinospora cordifolia on functions of peritoneal macrophages isolated from CCl4 intoxicated male albino mice,” BMC Complementary and Alternative Medicine, vol. 11, article 102, 2011. View at: Publisher Site | Google Scholar
  14. W. Z. Qin, H. W. Wei, and Z. H. Zhang, “The observation of curative effect on knee osteoarthritis through intra-articular injection of traditional Chinese drug ion-introduction coupled with triamcinolone acetonide about 78 cases,” New Journal of Traditional Chinese Medicine, vol. 38, no. 10, pp. 36–37, 2006. View at: Google Scholar
  15. Z. N. Liu, “Qutan tongluo recipe,” Guangxi Journal of Traditional Chinese Medicine, vol. 27, no. 3, p. 44, 2004. View at: Google Scholar
  16. H. S. Zhang, L. M. Zhang, and H. H. Zhang, “The observation of curative effect of knee ankylosis after injury auxiliary through huoxue Shujin Xunxi recipe,” Shaanxi Journal of Traditional Chinese Medicine, vol. 31, no. 8, pp. 997–998, 2010. View at: Google Scholar
  17. L. D. Wang, L. Huang, B. M. Zhao, and K. H. Zhang, “The observation of curative effect of adult humeral shaft fracture through integrated traditional Chinese and western medicine treatment,” New Journal of Traditional Chinese Medicine, vol. 37, no. 10, pp. 59–60, 2005. View at: Google Scholar
  18. M. X. Chen, Z. R. Li, and M. Z. Liang, “Treatment for supine and prone external ratationed ankle fracture,” Journal of Guangzhou University of Traditional Chinese Medicine, vol. 24, no. 6, pp. 456–458, 2007. View at: Google Scholar
  19. N. Singh, A. Kumar, P. Gupta et al., “Evaluation of antileishmanial potential of Tinospora sinensis against experimental visceral leishmaniasis,” Parasitology Research, vol. 102, no. 3, pp. 561–565, 2008. View at: Publisher Site | Google Scholar
  20. S. J. Li, J. Cheng, Y. Q. Han, and X. J. Liu, “The preparation and clinical application of Jinguo mixture,” Chinese Traditional Patent Medicine, vol. 31, no. 3, pp. 6–7, 2009. View at: Google Scholar
  21. H. Y. Zhang and W. F. Han, “The treatment of infusion phlebitis using immersion liquid of Tinospora capillipes on 78 cases,” Journal of External Therapy of Traditional Chinese Medicine, vol. 8, no. 6, p. 25, 1999. View at: Google Scholar
  22. W. K. Liu, Y. F. Zhao, and B. Y. Guan, “The preparation and application of Tinospora capillipes,” Jilin Journal of Traditional Chinese Medicine, no. 6, p. 31, 1990. View at: Google Scholar
  23. T. Z. Wang, L. L. Du, and C. Bai, “The research progress of Tinospora capillipes,” Journal of Chinese Medicinal Materials, vol. 25, no. 4, pp. 292–294, 2002. View at: Google Scholar
  24. F. X. Li, “Application research of Tinospora capillipes in veterinarian,” Sichuan Animal & Veterinary Sciences, no. 11, pp. 26–27, 2009. View at: Google Scholar
  25. F. R. Wu, C. Y. Zeng, and W. B. Dai, “Pharmacological effects of Tinospora sinensis and research progress in its clinical application,” China Licensed Pharmacist, vol. 11, no. 12, pp. 37–40, 2014. View at: Google Scholar
  26. J. Zeng, X. R. Zeng, and H. Y. Guan, “A comparative study of three medicine for Tinospora sinensis,” Journal of Medicine & Pharmacy of Chinese Minorities, no. 10, pp. 38–39, 2008. View at: Google Scholar
  27. T. S. Panchabhai, U. P. Kulkarni, and N. N. Rege, “Validation of therapeutic claims of Tinospora cordifolia: a review,” Phytotherapy Research, vol. 22, no. 4, pp. 425–441, 2008. View at: Publisher Site | Google Scholar
  28. N. Choudhary, M. B. Siddiqui, S. Azmat, and S. Khatoon, “Tinospora cordifolia: ethnobotany, phytopharmacology and phytochemistry aspects,” International Journal of Pharmaceutical Sciences and Research, vol. 4, no. 3, pp. 891–899, 2013. View at: Google Scholar
  29. Y. R. Sohni and R. M. Bhatt, “Activity of a crude extract formulation in experimental hepatic amoebiasis and in immunomodulation studies,” Journal of Ethnopharmacology, vol. 54, no. 2-3, pp. 119–124, 1996. View at: Publisher Site | Google Scholar
  30. S. A. Tasaduq, K. Singh, S. Sethi et al., “Hepatocurative and antioxidant profile of HP-1, a polyherbal phytomedicine,” Human and Experimental Toxicology, vol. 22, no. 12, pp. 639–645, 2003. View at: Publisher Site | Google Scholar
  31. H. Purandare and A. Supe, “Immunomodulatory role of Tinospora cordifolia as an adjuvant in surgical treatment of diabetic foot ulcers: a prospective randomized controlled study,” Indian Journal of Medical Sciences, vol. 61, no. 6, pp. 347–355, 2007. View at: Publisher Site | Google Scholar
  32. V. A. Badar, V. R. Thawani, P. T. Wakode et al., “Efficacy of Tinospora cordifolia in allergic rhinitis,” Journal of Ethnopharmacology, vol. 96, no. 3, pp. 445–449, 2005. View at: Publisher Site | Google Scholar
  33. Y. R. Sohni, P. Kaimal, and R. M. Bhatt, “The antiamoebic effect of a crude drug formulation of herbal extracts against Entamoeba histolytica in vitro and in vivo,” Journal of Ethnopharmacology, vol. 45, no. 1, pp. 43–52, 1995. View at: Publisher Site | Google Scholar
  34. A. Chopra, M. Saluja, G. Tillu et al., “Comparable efficacy of standardized Ayurveda formulation and hydroxychloroquine sulfate (HCQS) in the treatment of rheumatoid arthritis (RA): a randomized investigator-blind controlled study,” Clinical Rheumatology, vol. 31, no. 2, pp. 259–269, 2012. View at: Publisher Site | Google Scholar
  35. D. Krishnaiah, R. Sarbatly, and R. Nithyanandam, “A review of the antioxidant potential of medicinal plant species,” Food and Bioproducts Processing, vol. 89, no. 3, pp. 217–233, 2011. View at: Publisher Site | Google Scholar
  36. S. Jain, B. Sherlekar, and R. Barik, “Evaluation of antioxidant potential of Tinospora cordifolia and Tinospora sinensis,” International Journal of Pharmaceutical Sciences and Research, vol. 1, no. 11, pp. 122–128, 2010. View at: Google Scholar
  37. M. Sarala, V. Velu, C. Anandharamakrishnan, and R. P. Singh, “Spray drying of Tinospora cordifolia leaf and stem extract and evaluation of antioxidant activity,” Journal of Food Science and Technology, vol. 49, no. 1, pp. 119–122, 2012. View at: Publisher Site | Google Scholar
  38. A. Cavin, K. Hostettmann, W. Dyatmyko, and O. Potterat, “Antioxidant and lipophilic constituents of Tinospora crispa,” Planta Medica, vol. 64, no. 5, pp. 393–396, 1998. View at: Publisher Site | Google Scholar
  39. D. Naik, C. Dandge, and S. Rupanar, “Determination of chemical composition and evaluation of antioxidant activity of essential oil from Tinospora cordifolia (Willd.) Leaf,” Journal of Essential Oil-Bearing Plants, vol. 17, no. 2, pp. 228–236, 2014. View at: Publisher Site | Google Scholar
  40. L. S. Duvvuri, S. Katiyar, A. Kumar, and W. Khan, “Delivery aspects of antioxidants in diabetes management,” Expert Opinion on Drug Delivery, vol. 12, no. 5, pp. 827–844, 2015. View at: Publisher Site | Google Scholar
  41. T. Klangjareonchai, S. Putadechakum, and C. Roongpisuthipong, “Review of anti-hyperglycemic effect of Tinospora crispa,” Walailak Journal of Science and Technology, vol. 12, no. 5, pp. 403–406, 2015. View at: Google Scholar
  42. C.-T. Ruan, S.-H. Lam, T.-C. Chi, S.-S. Lee, and M.-J. Su, “Borapetoside C from Tinospora crispa improves insulin sensitivity in diabetic mice,” Phytomedicine, vol. 19, no. 8-9, pp. 719–724, 2012. View at: Publisher Site | Google Scholar
  43. C.-T. Ruan, S.-H. Lam, S.-S. Lee, and M.-J. Su, “Hypoglycemic action of borapetoside A from the plant Tinospora crispa in mice,” Phytomedicine, vol. 20, no. 8-9, pp. 667–675, 2013. View at: Publisher Site | Google Scholar
  44. F. E. Lokman, H. F. Gu, W. N. Wan Mohamud, M. M. Yusoff, K. L. Chia, and C.-G. Östenson, “Antidiabetic effect of oral borapetol B compound, isolated from the plant Tinospora crispa, by stimulating insulin release,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 727602, 7 pages, 2013. View at: Publisher Site | Google Scholar
  45. S. Mishra, N. Verma, S. Bhattacharya et al., “Effect of Tinospora cordifolia as an add-on therapy on the blood glucose levels of patients with type 2 diabetes,” International Journal of Basic & Clinical Pharmacology, vol. 4, no. 3, pp. 537–541, 2015. View at: Google Scholar
  46. S. Mishra, N. Verma, S. Bhattacharya et al., “Efficacy and safety of Tinospora cordifolia (Tc) as an add-on therapy in patients with type-2 diabetes,” International Journal of Research in Medical Sciences, vol. 3, no. 5, pp. 1109–1113, 2015. View at: Publisher Site | Google Scholar
  47. M. B. Patel and S. M. Mishra, “Magnoflorine from Tinospora cordifolia stem inhibits α-glucosidase and is antiglycemic in rats,” Journal of Functional Foods, vol. 4, no. 1, pp. 79–86, 2012. View at: Publisher Site | Google Scholar
  48. R. Kannadhasan and S. Venkataraman, “In vitro capacity and in vivo antioxidant potency of sedimental extract of Tinospora cordifolia in streptozotocin induced type 2 diabetes,” Avicenna Journal of Phytomedicine, vol. 3, no. 1, pp. 7–24, 2013. View at: Google Scholar
  49. N. Puranik, S. Devi Devi, and K. Kammar, “Hyperactivation of the hypothalamo-pituitary-Adrenocortical axis in streptozotocin diabetic rats: effect of Tinospora cordifolia (Willd.) and insulin therapy,” Turkish Journal of Medical Sciences, vol. 42, no. 6, pp. 1076–1081, 2012. View at: Publisher Site | Google Scholar
  50. P. K. Gupta, P. Chakraborty, S. Kumar et al., “G1-4A, a polysaccharide from Tinospora cordifolia inhibits the survival of Mycobacterium tuberculosis by modulating host immune responses in TLR4 dependent manner,” PLoS ONE, vol. 11, no. 5, Article ID e0154725, 2016. View at: Publisher Site | Google Scholar
  51. K. Ohtani, K. Okai, U. Yamashita, I. Yuasa, and A. Misaki, “Characterization of an acidic polysaccharide isolated from the leaves of Corchorus olitorius (Moroheiya),” Bioscience, Biotechnology, and Biochemistry, vol. 59, no. 3, pp. 378–381, 1995. View at: Publisher Site | Google Scholar
  52. E. A. Velazquez, D. Kimura, D. Torbati, C. Ramachandran, and B. R. Totapally, “Immunological response to (1,4)-α-D-glucan in the lung and spleen of endotoxin-stimulated juvenile rats,” Basic and Clinical Pharmacology and Toxicology, vol. 105, no. 5, pp. 301–306, 2009. View at: Publisher Site | Google Scholar
  53. R. Koppada, F. M. Norozian, D. Torbati, S. Kalomiris, C. Ramachandran, and B. R. Totapally, “Physiological effects of a novel immune stimulator drug, (1,4)-α-d-glucan, in rats,” Basic and Clinical Pharmacology and Toxicology, vol. 105, no. 4, pp. 217–221, 2009. View at: Publisher Site | Google Scholar
  54. V. Aher and A. K. Wahi, “Biotechnological approach to evaluate the immunomodulatory activity of ethanolic extract of Tinospora cordifoliastem (mango plant climber),” Iranian Journal of Pharmaceutical Research, vol. 11, no. 3, pp. 863–872, 2012. View at: Google Scholar
  55. P. K. R. Nair, S. Rodriguez, R. Ramachandran et al., “Immune stimulating properties of a novel polysaccharide from the medicinal plant Tinospora cordifolia,” International Immunopharmacology, vol. 4, no. 13, pp. 1645–1659, 2004. View at: Publisher Site | Google Scholar
  56. V. K. Pandey, B. S. Shankar, and K. B. Sainis, “G1-4 A, an arabinogalactan polysaccharide from Tinospora cordifolia increases dendritic cell immunogenicity in a murine lymphoma model,” International Immunopharmacology, vol. 14, no. 4, pp. 641–649, 2012. View at: Publisher Site | Google Scholar
  57. G. Chintalwar, A. Jain, A. Sipahimalani et al., “An immunologically active arabinogalactan from Tinospora cordifolia,” Phytochemistry, vol. 52, no. 6, pp. 1089–1093, 1999. View at: Publisher Site | Google Scholar
  58. R. Raghu, D. Sharma, R. Ramakrishnan, S. Khanam, G. J. Chintalwar, and K. B. Sainis, “Molecular events in the activation of B cells and macrophages by a non-microbial TLR4 agonist, G1-4A from Tinospora cordifolia,” Immunology Letters, vol. 123, no. 1, pp. 60–71, 2009. View at: Publisher Site | Google Scholar
  59. U. Bhardwaj, B. K. Tiwary, A. Prasad, and S. Ganguly, “Effect of Tinospora cordifolia extract on immune response and serum biochemical profile in broilers,” Indian Journal of Animal Sciences, vol. 82, no. 4, pp. 379–381, 2012. View at: Google Scholar
  60. C. P. Alexander, C. J. W. Kirubakaran, and R. D. Michael, “Water soluble fraction of Tinospora cordifolia leaves enhanced the non-specific immune mechanisms and disease resistance in Oreochromis mossambicus,” Fish & Shellfish Immunology, vol. 29, no. 5, pp. 765–772, 2010. View at: Publisher Site | Google Scholar
  61. U. Sharma, M. Bala, N. Kumar, B. Singh, R. K. Munshi, and S. Bhalerao, “Immunomodulatory active compounds from Tinospora cordifolia,” Journal of Ethnopharmacology, vol. 141, no. 3, pp. 918–926, 2012. View at: Publisher Site | Google Scholar
  62. W. N. Abood, I. Fahmi, M. A. Abdulla, and S. Ismail, “Immunomodulatory effect of an isolated fraction from Tinospora crispa on intracellular expression of INF-γ, IL-6 and IL-8,” BMC Complementary and Alternative Medicine, vol. 14, no. 1, article 205, 2014. View at: Publisher Site | Google Scholar
  63. A. Kapil and S. Sharma, “Immunopotentiating compounds from Tinospora cordifolia,” Journal of Ethnopharmacology, vol. 58, no. 2, pp. 89–95, 1997. View at: Publisher Site | Google Scholar
  64. S. Jiang, L. M. Qiu, L. Li et al., “Effects of Marsdenia tenacissima polysaccharide on the immune regulation and tumor growth in H22 tumor-bearing mice,” Carbohydrate Polymers, vol. 137, pp. 52–58, 2016. View at: Publisher Site | Google Scholar
  65. P. M. P. Ferreira, G. C. G. Militão, D. J. B. Lima et al., “Morphological and biochemical alterations activated by antitumor clerodane diterpenes,” Chemico-Biological Interactions, vol. 222, pp. 112–125, 2014. View at: Publisher Site | Google Scholar
  66. A. M. Prieto, A. G. dos Santos, A. P. S. Oliveira et al., “Assessment of the chemopreventive effect of casearin B, a clerodane diterpene extracted from Casearia sylvestris (Salicaceae),” Food and Chemical Toxicology, vol. 53, pp. 153–159, 2013. View at: Publisher Site | Google Scholar
  67. P. R. F. De Carvalho, M. Furlan, M. C. M. Young, D. G. I. Kingston, and V. D. S. Bolzani, “Acetylated DNA-damaging clerodane diterpenes from Casearia sylvestris,” Phytochemistry, vol. 49, no. 6, pp. 1659–1662, 1998. View at: Publisher Site | Google Scholar
  68. R. Mishra and G. Kaur, “Aqueous ethanolic extract of Tinospora cordifolia as a potential candidate for differentiation based therapy of glioblastomas,” PLoS ONE, vol. 8, no. 10, Article ID e78764, pp. 1–13, 2013. View at: Publisher Site | Google Scholar
  69. P. More and K. Pai, “In vitro NADH-oxidase, NADPH-oxidase and myeloperoxidase activity of macrophages after Tinospora cordifolia (guduchi) treatment,” Immunopharmacology and Immunotoxicology, vol. 34, no. 3, pp. 368–372, 2012. View at: Publisher Site | Google Scholar
  70. J. W. Liang, T. J. Zhang, Z. J. Li, Z. X. Chen, X. L. Yan, and F. H. Meng, “Predicting potential antitumor targets of Aconitum alkaloids by molecular docking and protein-ligand interaction fingerprint,” Medicinal Chemistry Research, vol. 25, no. 6, pp. 1115–1124, 2016. View at: Publisher Site | Google Scholar
  71. H. Ali and S. Dixit, “Extraction optimization of Tinospora cordifolia and assessment of the anticancer activity of its alkaloid palmatine,” The Scientific World Journal, vol. 2013, Article ID 376216, 10 pages, 2013. View at: Publisher Site | Google Scholar
  72. P. K. R. Nair, S. J. Melnick, R. Ramachandran, E. Escalon, and C. Ramachandran, “Mechanism of macrophage activation by (1,4)-α-d-glucan isolated from Tinospora cordifolia,” International Immunopharmacology, vol. 6, no. 12, pp. 1815–1824, 2006. View at: Publisher Site | Google Scholar
  73. V. Sonaimuthu, S. Krishnamoorthy, and M. Johnpaul, “Taxol producing endophytic fungus Fusarium culmorum SVJM072 from medicinal plant of Tinospora cordifolia—a first report,” Journal of Biotechnology, vol. 150, supplement, p. 425, 2010. View at: Publisher Site | Google Scholar
  74. A. Jungbauer and S. Medjakovic, “Anti-inflammatory properties of culinary herbs and spices that ameliorate the effects of metabolic syndrome,” Maturitas, vol. 71, no. 3, pp. 227–239, 2012. View at: Publisher Site | Google Scholar
  75. Q. Xu, Y. Wang, S. Guo, Z. Shen, Y. Wang, and L. Yang, “Anti-inflammatory and analgesic activity of aqueous extract of Flos populi,” Journal of Ethnopharmacology, vol. 152, no. 3, pp. 540–545, 2014. View at: Publisher Site | Google Scholar
  76. Y. C. Deng, M. Zhang, and H. Y. Luo, “Identification and antimicrobial activity of two alkaloids from traditional Chinese medicinal plant Tinospora capillipes,” Industrial Crops and Products, vol. 37, no. 1, pp. 298–302, 2012. View at: Publisher Site | Google Scholar
  77. M. F. Khalilsaraie, N. Saima, N. T. Meti, R. K. Bhadekar, and D. P. Nerkar, “Cytological study and anti-microbial activity of embryogenic callus induced from leaf cultures of Tinospora cordifolia (Willd.) Miers,” Journal of Medicinal Plant Research, vol. 5, no. 14, pp. 3002–3006, 2011. View at: Google Scholar
  78. J. M. Bhagyasree, H. J. Hrishikeshavan, P. Krishnamoorthy et al., “Cytoprotective influence of ethanolic stem extract of Tinospora cardifolia on the inflammatory bowel disease,” International Journal of Advanced Research, vol. 4, no. 4, pp. 179–187, 2016. View at: Publisher Site | Google Scholar
  79. N.-D. Zhang, T. Han, B.-K. Huang et al., “Traditional Chinese Medicine formulas for the treatment of osteoporosis: implication for antiosteoporotic drug discovery,” Journal of Ethnopharmacology, vol. 189, pp. 61–80, 2016. View at: Publisher Site | Google Scholar
  80. L. Gao, G. P. Cai, and X. J. Shi, “β-ecdysterone induces osteogenic differentiation in mouse mesenchymal stem cells and relieves osteoporosis,” Biological and Pharmaceutical Bulletin, vol. 31, no. 12, pp. 2245–2249, 2008. View at: Publisher Site | Google Scholar
  81. G. Abiramasundari, K. R. Sumalatha, and M. Sreepriya, “Effects of Tinospora cordifolia (Menispermaceae) on the proliferation, osteogenic differentiation and mineralization of osteoblast model systems in vitro,” Journal of Ethnopharmacology, vol. 141, no. 1, pp. 474–480, 2012. View at: Publisher Site | Google Scholar
  82. A. Patel, P. Bigoniya, C. S. Singh, and N. S. Patel, “Radioprotective and cytoprotective activity of Tinospora cordifolia stem enriched extract containing cordifolioside-A,” Indian Journal of Pharmacology, vol. 45, no. 3, pp. 237–243, 2013. View at: Publisher Site | Google Scholar
  83. L. Singh, S. Tyagi, M. A. Rizvi, and H. C. Goel, “Effect of Tinospora cordifolia on gamma ray-induced perturbations in macrophages and splenocytes,” Journal of Radiation Research, vol. 48, no. 4, pp. 305–315, 2007. View at: Publisher Site | Google Scholar
  84. S. K. Rao, P. S. Rao, and B. N. Rao, “Preliminary investigation of the radiosensitizing activity of Guduchi (Tinospora cordifolia) in tumor-bearing mice,” Phytotherapy Research, vol. 22, no. 11, pp. 1482–1489, 2008. View at: Publisher Site | Google Scholar
  85. H. Sachdeva, R. Sehgal, and S. Kaur, “Tinospora cordifolia as a protective and immunomodulatory agent in combination with cisplatin against murine visceral leishmaniasis,” Experimental Parasitology, vol. 137, no. 1, pp. 53–65, 2014. View at: Publisher Site | Google Scholar
  86. M. Yusoff, H. Hamid, and P. Houghton, “Anticholinesterase inhibitory activity of quaternary alkaloids from Tinospora crispa,” Molecules, vol. 19, no. 1, pp. 1201–1211, 2014. View at: Publisher Site | Google Scholar
  87. J. Kosaraju, S. Chinni, P. D. Roy, E. Kannan, A. S. Antony, and M. N. S. Kumar, “Neuroprotective effect of Tinospora cordifolia ethanol extract on 6-hydroxy dopamine induced Parkinsonism,” Indian Journal of Pharmacology, vol. 46, no. 2, pp. 176–180, 2014. View at: Publisher Site | Google Scholar
  88. A. Gupta, H. Raj, M. S. Karchuli, and N. Upmanyu, “Comparative evaluation of ethanolic extracts of Bacopa monnieri, Evolvulus alsinoides, Tinospora cordifolia and their combinations on cognitive functions in rats,” Current Aging Science, vol. 6, no. 3, pp. 239–243, 2013. View at: Publisher Site | Google Scholar
  89. J. Jiang, Z. X. Liao, and M. Ji, “The review about structure characteristics and NMR data of clerodane-type diterpenoids,” Chemical Industry Times, vol. 21, no. 12, pp. 49–53, 2007. View at: Google Scholar
  90. S. C. Butler and C. J. Forsyth, “A stereoconvergent intramolecular Diels-Alder cycloaddition related to the construction of the decalin core of neo-clerodane diterpenoids,” The Journal of Organic Chemistry, vol. 78, no. 8, pp. 3895–3907, 2013. View at: Publisher Site | Google Scholar
  91. M. I. Choudhary, M. Ismail, K. Shaari et al., “Cis- clerodane-type furanoditerpenoids from Tinospora crispa,” Journal of Natural Products, vol. 73, no. 4, pp. 541–547, 2010. View at: Publisher Site | Google Scholar
  92. L.-M. Shi, R.-Q. Li, and W.-H. Liu, “Two new furanoid diterpenoids from Tinospora sagittata,” Helvetica Chimica Acta, vol. 91, no. 5, pp. 978–982, 2008. View at: Publisher Site | Google Scholar
  93. X.-Z. Huang, C.-M. Cheng, Y. Dai et al., “A novel 18-Norclerodane diterpenoid from the roots of Tinospora sagittata var. yunnanensis,” Molecules, vol. 15, no. 11, pp. 8360–8365, 2010. View at: Publisher Site | Google Scholar
  94. P. Van Kiem, C. Van Minh, N. T. Dat et al., “Aporphine alkaloids, clerodane diterpenes, and other constituents from Tinospora cordifolia,” Fitoterapia, vol. 81, no. 6, pp. 485–489, 2010. View at: Publisher Site | Google Scholar
  95. N. Fukuda, M. Yonemitsu, and T. Kimura, “Isolation and structure elucidation of the new furanoid diterpene glucoside borapetoside H,” Liebigs Annalen der Chemie, vol. 26, no. 50, pp. 1689–1691, 1995. View at: Google Scholar
  96. Y. C. Koay and F. Amir, “A review of the secondary metabolites and biological activities of Tinospora crispa (Menispermaceae),” Tropical Journal of Pharmaceutical Research, vol. 12, no. 4, pp. 641–649, 2013. View at: Publisher Site | Google Scholar
  97. Z. Y. Jiang, W. J. Li, L. X. Jiao et al., “New clerodane diterpenes from Tinospora sagittata var. yunnanensis,” Planta Medica, vol. 80, no. 5, pp. 419–425, 2014. View at: Google Scholar
  98. W. Li, C. Huang, S. P. Li et al., “Clerodane diterpenoids from Tinospora sagittata (Oliv) gagnep,” Planta Medica, vol. 78, no. 1, pp. 82–85, 2012. View at: Publisher Site | Google Scholar
  99. V. Wazir, R. Maurya, and R. S. Kapil, “Cordioside, a clerodane furano diterpene glucoside from Tinospora cordifolia,” Phytochemistry, vol. 38, no. 2, pp. 447–449, 1995. View at: Publisher Site | Google Scholar
  100. V. D. Gangan, P. Pradhan, A. T. Sipahimalani, and A. Banerji, “Norditerpene furan glycosides from Tinospora cordifolia,” Phytochemistry, vol. 39, no. 5, pp. 1139–1142, 1995. View at: Publisher Site | Google Scholar
  101. W. Li, K. Wei, H. Fu, and K. Koike, “Structure and absolute configuration of clerodane diterpene glycosides and a rearranged cadinane sesquiterpene glycoside from the stems of Tinospora sinensis,” Journal of Natural Products, vol. 70, no. 12, pp. 1971–1976, 2007. View at: Publisher Site | Google Scholar
  102. F. Ahmad, M. Ali, and P. Alam, “New phytoconstituents from the stem bark of Tinospora cordifolia Miers,” Natural Product Research, vol. 24, no. 10, pp. 926–934, 2010. View at: Publisher Site | Google Scholar
  103. L.-P. Dong, C.-X. Chen, W. Ni, B.-B. Xie, J.-Z. Li, and H.-Y. Liu, “A new dinorclerone diterpenoid glycoside from Tinospora sinensis,” Natural Product Research, vol. 24, no. 1, pp. 13–17, 2010. View at: Publisher Site | Google Scholar
  104. M. Yonemitsu, N. Fukuda, T. Kimura, R. Isobe, and T. Komori, “Isolation and structure elucidation of two new dinorditerpene glucosides, tinosineside A and B,” Liebigs Annalen, vol. 1995, no. 2, pp. 437–439, 1995. View at: Google Scholar
  105. C. Huang, W. Li, F. H. Ma, Q. Li, Y. Asada, and K. Koike, “Tinospinosides D, E, and Tinospin E, further clerodane diterpenoids from Tinospora sagittata,” Chemical and Pharmaceutical Bulletin, vol. 60, no. 10, pp. 1324–1328, 2012. View at: Publisher Site | Google Scholar
  106. S. Q. Rong, Y. H. Shen, C. Zhang, R. H. Liu, and W. D. Zhang, “Chemical constituents of two original plants used as radix Tinosporae,” Chinese Journal of Natural Medicines, vol. 6, no. 3, pp. 186–189, 2008. View at: Google Scholar
  107. Z.-J. Zhan, X.-Y. Zhang, X.-R. Hou, C.-P. Li, and W.-G. Shan, “New diterpenoids from Tinospora capillipes,” Helvetica Chimica Acta, vol. 92, no. 4, pp. 790–794, 2009. View at: Publisher Site | Google Scholar
  108. L. Pan, C. Terrazas, C. M. Lezama-Davila et al., “Cordifolide A, a sulfur-containing clerodane diterpene glycoside from Tinospora cordifolia,” Organic Letters, vol. 14, no. 8, pp. 2118–2121, 2012. View at: Publisher Site | Google Scholar
  109. R. Maurya, L. R. Manhas, P. Gupta, P. K. Mishra, G. Singh, and P. P. Yadav, “Amritosides A, B, C and D: clerodane furano diterpene glucosides from Tinospora cordifolia,” Phytochemistry, vol. 65, no. 14, pp. 2051–2055, 2004. View at: Publisher Site | Google Scholar
  110. M. Dhanasekaran, A.-A. Baskar, S. Ignacimuthu, P. Agastian, and V. Duraipandiyan, “Chemopreventive potential of Epoxy clerodane diterpene from Tinospora cordifolia against diethylnitrosamine-induced hepatocellular carcinoma,” Investigational New Drugs, vol. 27, no. 4, pp. 347–355, 2009. View at: Publisher Site | Google Scholar
  111. P. Antonisamy, M. Dhanasekaran, S. Ignacimuthu et al., “Gastroprotective effect of epoxy clerodane diterpene isolated from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in rats,” Phytomedicine, vol. 21, no. 7, pp. 966–969, 2014. View at: Publisher Site | Google Scholar
  112. X.-Z. Huang, C.-M. Cheng, Y. Dai et al., “A novel lignan glycoside with antioxidant activity from Tinospora sagittata var. yunnanensis,” Natural Product Research, vol. 26, no. 20, pp. 1876–1880, 2012. View at: Publisher Site | Google Scholar
  113. R. Maurya, V. Wazir, A. Tyagi, and R. S. Kapil, “Clerodane diterpenoids from Tinospora cordifolia,” Phytochemistry, vol. 38, no. 3, pp. 659–661, 1995. View at: Publisher Site | Google Scholar
  114. N. L. Hungerford, D. P. A. Sands, and W. Kitching, “Isolation and structure of some constituents of the Australian medicinal plant Tinospora smilacina (‘Snakevine’),” Australian Journal of Chemistry, vol. 51, no. 12, pp. 1103–1111, 1998. View at: Publisher Site | Google Scholar
  115. C. Y. Ragasa, M. C. Cruz, R. Gula, and J. A. Rideout, “Clerodane diterpenes from Tinospora rumphii,” Journal of Natural Products, vol. 63, no. 4, pp. 509–511, 2000. View at: Publisher Site | Google Scholar
  116. N. Fukuda, M. Nakamura, M. Yonemitsu, T. Kimura, R. Isobe, and T. Komori, “Isolation and structure elucidation of two new furanoid diterpenes, Tinotufolin A and B,” Liebigs Annalen der Chemie, vol. 1993, no. 3, pp. 325–327, 1993. View at: Google Scholar
  117. T. S. Martin, K. Ohtani, R. Kasai, and K. Yamasaki, “Clerodane diterpene glucosides from Tinospora rumphii,” Phytochemistry, vol. 40, no. 6, pp. 1729–1736, 1995. View at: Publisher Site | Google Scholar
  118. T. S. Martin, K. Ohtani, R. Kasai, and K. Yamasaki, “Furanoid diterpene glucosides from Tinospora rumphii,” Phytochemistry, vol. 42, no. 1, pp. 153–158, 1996. View at: Publisher Site | Google Scholar
  119. P. Tuntiwachwuttikul and W. C. Taylor, “New rearranged clerodane diterpenes from Tinospora baenzigeri,” Chemical and Pharmaceutical Bulletin, vol. 49, no. 7, pp. 854–857, 2001. View at: Publisher Site | Google Scholar
  120. N. Kongkathip, P. Dhumma-upakorn, B. Kongkathip, K. Chawananoraset, P. Sangchomkaeo, and S. Hatthakitpanichakul, “Study on cardiac contractility of cycloeucalenol and cycloeucalenone isolated from Tinospora crispa,” Journal of Ethnopharmacology, vol. 83, no. 1-2, pp. 95–99, 2002. View at: Publisher Site | Google Scholar
  121. S. Ghosal and R. A. Vishwakarma, “Tinocordiside, a new rearranged cadinane sesquiterpene glycoside from Tinospora cordifolia,” Journal of Natural Products, vol. 60, no. 8, pp. 839–841, 1997. View at: Publisher Site | Google Scholar
  122. R. Maurya, K. L. Dhar, and S. S. Handa, “A sesquiterpene glucoside from Tinospora cordifolia,” Phytochemistry, vol. 44, no. 4, pp. 749–750, 1997. View at: Publisher Site | Google Scholar
  123. B. Wang, P.-L. Zhang, M.-X. Zhou et al., “New nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capillipes,” Phytochemistry Letters, vol. 15, pp. 225–229, 2016. View at: Publisher Site | Google Scholar
  124. A. Sivasubramanian, K. K. G. Narasimha, R. Rathnasamy, and A. M. F. O. Campos, “A new antifeedant clerodane diterpenoid from Tinospora cordifolia,” Natural Product Research, vol. 27, no. 16, pp. 1431–1436, 2013. View at: Publisher Site | Google Scholar
  125. G. Zhang, H. Ma, S. Hu et al., “Clerodane-type diterpenoids from tuberous roots of Tinospora sagittata (Oliv.) Gagnep,” Fitoterapia, vol. 110, pp. 59–65, 2016. View at: Publisher Site | Google Scholar
  126. N. Fukuda, M. Yonemitsu, and T. Kimura, “Studies on the constituents of the stems of Tinospora tuberculata BEUMEE III.1) new dterpenoids borapetoside B and borapetol B,” Chemical and Pharmaceutical Bulletin, vol. 34, no. 7, pp. 2868–2872, 1986. View at: Google Scholar
  127. A. U. Rahman, S. S. Ali, S. Ahmad, and M. I. Choudhary, “A furanoid diterpene from Tinospora malabarica,” Phytochemistry, vol. 31, no. 9, pp. 3155–3157, 1992. View at: Publisher Site | Google Scholar
  128. N. Fukuda, M. Yonemitsu, and T. Kimura, “Isolation and structure elucidation of the five new furanoid diterpene glycosides borapetoside C-G,” Chemical and Pharmaceutical Bulletin, vol. 24, no. 37, pp. 156–161, 1993. View at: Google Scholar
  129. S.-H. Lam, C.-T. Ruan, P.-H. Hsieh, M.-J. Su, and S.-S. Lee, “Hypoglycemic diterpenoids from Tinospora crispa,” Journal of Natural Products, vol. 75, no. 2, pp. 153–159, 2012. View at: Publisher Site | Google Scholar
  130. R. K. Bhatt and B. K. Sabata, “A furanoid diterpene glucoside from Tinospora cordifolia,” Phytochemistry, vol. 28, no. 9, pp. 2419–2422, 1989. View at: Publisher Site | Google Scholar
  131. Atta-ur-Rahman and S. Ahmad, “A furanoid diterpene, 10 α-hydroxycolumbin, from Tinospora malabarica,” Phytochemistry, vol. 27, no. 6, pp. 1882–1884, 1988. View at: Publisher Site | Google Scholar
  132. N.-B. Qin, A.-L. Wang, D.-H. Li et al., “Cytotoxic clerodane furanoditerpenoids from the root of Tinospora sagittata,” Phytochemistry Letters, vol. 12, pp. 173–176, 2015. View at: Publisher Site | Google Scholar
  133. H. B. Li, J. Hu, J. C. Chen, and M. H. Qiu, “Chemical constituents of Tinospora craveniana,” Natural Product Research and Development, vol. 17, no. 2, pp. 125–127, 2005. View at: Google Scholar
  134. N. Fukuda, M. Yonemitsu, T. Kimura, S. Hachiyama, K. Miyahara, and T. Kawasaki, “Studies on the constituents of the stems of Tinospora tubereulata BEUMÉE. II.1) new diterpenoids, borapetoside A and borapetol A,” Chemical & Pharmaceutical Bulletin, vol. 33, no. 10, pp. 4438–4444, 1985. View at: Publisher Site | Google Scholar
  135. U. Sharma, M. Bala, R. Saini et al., “Polysaccharide enriched immunomodulatory fractions from Tinospora cordifolia (Willd) miers ax hook. F. & Thoms,” Indian Journal of Experimental Biology, vol. 50, no. 9, pp. 612–617, 2012. View at: Google Scholar
  136. R. Maurya and S. S. Handa, “Tinocordifolin, a sesquiterpene from Tinospora cordifolia,” Phytochemistry, vol. 49, no. 5, pp. 1343–1345, 1998. View at: Publisher Site | Google Scholar
  137. N. G. Bisset and J. Nwaiwu, “Quaternary alkaloids of Tinospora species,” Planta Medica, vol. 48, no. 4, pp. 275–279, 1983. View at: Publisher Site | Google Scholar
  138. H. M. Chang, A. M. El-Fishawy, D. J. Slatkin, and P. L. Schiff Jr., “Quaternary alkaloids of Tinospora capillipes,” Planta Medica, vol. 50, no. 1, pp. 88–90, 1984. View at: Publisher Site | Google Scholar
  139. Y. F. Zhang, Q. R. Shi, P. Y. Shi, W. D. Zhang, and Y. Y. Cheng, “Characterization of isoquinoline alkaloids, diterpenoids and steroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittata and Tinospora capillipes) by high-performance liquid chromatography/electrospray ionization with multistage mass spectrometry,” Rapid Communications in Mass Spectrometry, vol. 20, no. 15, pp. 2328–2342, 2006. View at: Publisher Site | Google Scholar
  140. R. Maurya, P. Gupta, K. Chand et al., “Constituents of Tinospora sinensis and their antileishmanial activity against Leishmania donovani,” Natural Product Research, vol. 23, no. 12, pp. 1134–1143, 2009. View at: Publisher Site | Google Scholar
  141. Y. Y. Guo, L. B. Lin, X. W. Fu, K. Keisuke, and O. Yukio, “Studies on alkaloids from Tinospora hainanesis,” Journal of Hainan Medical College, vol. 10, no. 5, pp. 293–297, 2004. View at: Google Scholar
  142. S. Praman, M. J. Mulvany, D. E. Williams, R. J. Andersen, and C. Jansakul, “Hypotensive and cardio-chronotropic constituents of Tinospora crispa and mechanisms of action on the cardiovascular system in anesthetized rats,” Journal of Ethnopharmacology, vol. 140, no. 1, pp. 166–178, 2012. View at: Publisher Site | Google Scholar
  143. R. A. Barraco, D. R. Marcantonio, J. W. Phillis, and W. R. Campbell, “The effects of parenteral injections of adenosine and its analogs on blood pressure and heart rate in the rat,” General Pharmacology, vol. 18, no. 4, pp. 405–416, 1987. View at: Publisher Site | Google Scholar
  144. F. Samita, C. O. Ochieng, P. O. Owuor, and L. A. O. Manguro, “New ceramide from the aerial part of Tinospora oblongifolia with cytotoxic activities,” Natural Product Research, vol. 28, no. 9, pp. 661–666, 2014. View at: Publisher Site | Google Scholar
  145. P. Pushp, N. Sharma, G. S. Joseph, and R. P. Singh, “Antioxidant activity and detection of (−)epicatechin in the methanolic extract of stem of Tinospora cordifolia,” Journal of Food Science and Technology, vol. 50, no. 3, pp. 567–572, 2013. View at: Publisher Site | Google Scholar
  146. C.-C. Chang, S. L. Ho, and S.-S. Lee, “Acylated glucosylflavones as α-glucosidase inhibitors from Tinospora crispa leaf,” Bioorganic and Medicinal Chemistry, vol. 23, no. 13, pp. 3388–3396, 2015. View at: Publisher Site | Google Scholar
  147. P. Tuntiwachwuttikul, N. Boonrasri, J. B. Bremner, and W. C. Taylor, “Rearranged clerodane diterpenes from Tinospora baenzigeri,” Phytochemistry, vol. 52, no. 7, pp. 1335–1340, 1999. View at: Publisher Site | Google Scholar
  148. Y. Y. Guo, K. Kojima, L. B. Lin et al., “A new N-methyltetrahydroprotoberberine alkaloid from Tinospora hainanensis,” Chemical and Pharmaceutical Bulletin, vol. 47, no. 2, pp. 287–289, 1999. View at: Publisher Site | Google Scholar
  149. T. Yokozawa, T. S. Wang, C. P. Chen, and M. Hattori, “Inhibition of nitric oxide release by an aqueous extract of Tinospora tuberculata,” Phytotherapy Research, vol. 14, no. 1, pp. 51–53, 2000. View at: Google Scholar
  150. T. Yokozawa, T. Tanaka, and T. Kimura, “Examination of the nitric oxide production-suppressing component in Tinospora tuberculata,” Biological and Pharmaceutical Bulletin, vol. 24, no. 10, pp. 1153–1156, 2001. View at: Publisher Site | Google Scholar
  151. M. Jahfar, “Glycosyl composition of polysaccharide from Tinospora cordifolia,” Acta Pharmaceutica, vol. 53, no. 1, pp. 65–69, 2003. View at: Google Scholar
  152. U. Sharma, P. Bhandari, N. Kumar, and B. Singh, “Simultaneous determination of ten sugars in Tinospora cordifolia by ultrasonic assisted extraction and LC-ELSD,” Chromatographia, vol. 71, no. 7-8, pp. 633–638, 2010. View at: Publisher Site | Google Scholar
  153. M. Jahfar and P. Azadi, “Glycosyl composition of polysaccharide from Tinospora cordifolia. II. glycosyl linkages,” Acta Pharmaceutica, vol. 54, no. 1, pp. 73–78, 2004. View at: Google Scholar
  154. P. V. Leyon and G. Kuttan, “Inhibitory effect of a polysaccharide from Tinospora cordifolia on experimental metastasis,” Journal of Ethnopharmacology, vol. 90, no. 2-3, pp. 233–237, 2004. View at: Publisher Site | Google Scholar
  155. Q. R. Shi, M. J. Liang, W. D. Zhang et al., “Quantitative LC/MS/MS method and pharmacokinetic studies of columbin, an anti-inflammation furanoditerpen isolated from radix Tinosporae,” Biomedical Chromatography, vol. 21, no. 6, pp. 642–648, 2007. View at: Publisher Site | Google Scholar
  156. S. Gandhi, M. M. Devi, S. Pal, R. P. Tripathi, and S. Khushu, “Metabolic regulatory variations in rats due to acute cold stress & Tinospora cordifolia intervention: high resolution 1H NMR approach,” Metabolomics, vol. 8, no. 3, pp. 444–453, 2012. View at: Publisher Site | Google Scholar
  157. N. N. Rege, U. M. Thatte, and S. A. Dahanukar, “Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine,” Phytotherapy Research, vol. 13, no. 4, pp. 275–291, 1999. View at: Publisher Site | Google Scholar
  158. A. Agarwal, S. Malini, K. L. Bairy, and M. S. Rao, “Effect of Tinospora cordifolia on learning and memory in normal and memory deficit rats,” Indian Journal of Pharmacology, vol. 34, no. 5, pp. 339–349, 2002. View at: Google Scholar
  159. P. N. Manjrekar, C. I. Jolly, and S. Narayanan, “Comparative studies of the immunomodulatory activity of Tinospora cordifolia and Tinospora sinensis,” Fitoterapia, vol. 71, no. 3, pp. 254–257, 2000. View at: Publisher Site | Google Scholar
  160. C. V. Chandrasekaran, L. N. Mathuram, P. Daivasigamani, and U. Bhatnagar, “Tinospora cordifolia, a safety evaluation,” Toxicology in Vitro, vol. 23, no. 7, pp. 1220–1226, 2009. View at: Publisher Site | Google Scholar
  161. Y. R. Karkal and L. K. Bairy, “Safety of aqueous extract of Tinospora cordifolia (Tc) in healthy volunteers: a double blind randomised placebo controlled study,” Iranian Journal of Pharmacology and Therapeutics, vol. 6, no. 1, pp. 59–61, 2007. View at: Google Scholar
  162. S. S. Nayampalli, S. S. Ainapure, B. D. Samant, R. G. Kudtarkar, N. K. Desai, and K. C. Gupta, “A comparative study of diuretic effects of Tinospora cordifolia and hydrochlorothiazide in rats and a preliminary phase I study in human volunteers,” Journal of Postgraduate Medicine, vol. 34, no. 4, pp. 233–236, 1988. View at: Google Scholar
  163. A. K. Upadhyay, K. Kumar, A. Kumar, and H. S. Mishra, “Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi)—validation of the Ayurvedic pharmacology through experimental and clinical studies,” International Journal of Ayurveda Research, vol. 1, no. 2, pp. 112–121, 2010. View at: Publisher Site | Google Scholar

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