Advances in Pharmacological Sciences The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Involvement of Inflammatory Cytokines in Antiarrhythmic Effects of Clofibrate in Ouabain-Induced Arrhythmia in Isolated Rat Atria Wed, 10 Feb 2016 12:08:03 +0000 Considering the cardioprotective and anti-inflammatory properties of clofibrate, the aim of the present experiment was to investigate the involvement of local and systemic inflammatory cytokines in possible antiarrhythmic effects of clofibrate in ouabain-induced arrhythmia in rats. Rats were orally treated with clofibrate (300 mg/kg), and ouabain (0.56 mg/kg) was administered to animals intraperitoneally. After induction of anesthesia, the atria were isolated and the onset of arrhythmia and asystole was recorded. The levels of inflammatory cytokines in atria were also measured. Clofibrate significantly postponed the onset of arrhythmia and asystole when compared to control group ( and , resp.). While ouabain significantly increased the atrial beating rate in control group (), same treatment did not show similar effect in clofibrate-treated group (). Injection of ouabain significantly increased the atrial and systemic levels of all studied inflammatory cytokines (). Pretreatment with clofibrate could attenuate the ouabain-induced elevation of IL-6 and TNF-α in atria ( and , resp.), as well as ouabain-induced increase in IL-6 in plasma (). Based on our findings, clofibrate may possess antiarrhythmic properties through mitigating the local and systemic inflammatory factors including IL-6 and TNF-α. Somayeh Moradi, Vahid Nikoui, Muhammad Imran Khan, Shayan Amiri, Farahnaz Jazaeri, and Azam Bakhtiarian Copyright © 2016 Somayeh Moradi et al. All rights reserved. Methanolic Extract of Ceplukan Leaf (Physalis minima L.) Attenuates Ventricular Fibrosis through Inhibition of TNF-α in Ovariectomized Rats Sun, 31 Jan 2016 14:01:12 +0000 The increase of heart failure prevalence on menopausal women was correlated with the decrease of estrogen level. The aim of this study is to investigate the effects of ceplukan leaf (Physalis minima L.), which contains phytoestrogen physalin and withanolides, on ventricular TNF-α level and fibrosis in ovariectomized rats. Wistar rats were divided into six groups (control (—); OVX 5: 5-week ovariectomy (OVX); OVX 9: 9-week ovariectomy; treatments I, II, and III: 9-weeks OVX + 4-week ceplukan leaf’s methanolic extract doses 500, 1500, and 2500 mg/kgBW, resp.). TNF-α levels were measured with ELISA. Fibrosis was counted as blue colored tissues percentage using Masson’s Trichrome staining. This study showed that prolonged hypoestrogen increases ventricular fibrosis (). Ceplukan leaf treatment also resulted in a decrease of ventricular fibrosis and TNF-α level in dose dependent manner compared to without treatment group (). Furthermore, the TNF-α level was normalized in 2500 mg/kgBW Physalis minima L. () treatment. The reduction of fibrosis positively correlated with TNF-α level (, ). Methanolic extract of ceplukan leaf decreases ventricular fibrosis through the inhibition of ventricular TNF-α level in ovariectomized rats. Bayu Lestari, Nur Permatasari, and Mohammad Saifur Rohman Copyright © 2016 Bayu Lestari et al. All rights reserved. A Review on Potential Mechanisms of Terminalia chebula in Alzheimer’s Disease Thu, 28 Jan 2016 09:19:33 +0000 The current management of Alzheimer’s disease (AD) focuses on acetylcholinesterase inhibitors (AChEIs) and NMDA receptor antagonists, although outcomes are not completely favorable. Hence, novel agents found in herbal plants are gaining attention as possible therapeutic alternatives. The Terminalia chebula (Family: Combretaceae) is a medicinal plant with a wide spectrum of medicinal properties and is reported to contain various biochemicals such as hydrolysable tannins, phenolic compounds, and flavonoids, so it may prove to be a good therapeutic alternative. In this research, we reviewed published scientific literature found in various databases: PubMed, Science Direct, Scopus, Web of Science, Scirus, and Google Scholar, with the keywords: T. chebula, AD, neuroprotection, medicinal plant, antioxidant, ellagitannin, gallotannin, gallic acid, chebulagic acid, and chebulinic acid. This review shows that T. chebula extracts and its constituents have AChEI and antioxidant and anti-inflammatory effects, all of which are currently relevant to the treatment of Alzheimer’s disease. Amir R. Afshari, Hamid R. Sadeghnia, and Hamid Mollazadeh Copyright © 2016 Amir R. Afshari et al. All rights reserved. Protective Effect of Diospyros kaki against Glucose-Oxygen-Serum Deprivation-Induced PC12 Cells Injury Thu, 28 Jan 2016 06:02:57 +0000 Ischemic cerebrovascular disease is one of the most common causes of death in the world. Recent interests have been focused on natural antioxidants and anti-inflammatory agents as potentially useful neuroprotective agents. Diospyros kaki (persimmon) has been shown to exert anti-inflammatory, antioxidant, and antineoplastic effects. However, its effects on ischemic damage have not been evaluated. Here, we used an in vitro model of cerebral ischemia and studied the effects of hydroalcoholic extract of peel (PeHE) and fruit pulp (PuHE) of persimmon on cell viability and markers of oxidative damage mainly intracellular reactive oxygen species (ROS) induced by glucose-oxygen-serum deprivation (GOSD) in PC12 cells. GOSD for 6 h produced significant cell death which was accompanied by increased levels of ROS. Pretreatment with different concentrations of PeHE and PuHE (0–500 μg/mL) for 2 and 24 h markedly restored these changes only at high concentrations. However, no significant differences were seen in the protection against ischemic insult between different extracts and the time of exposure. The experimental results suggest that persimmon protects the PC12 cells from GOSD-induced injury via antioxidant mechanisms. Our findings might raise the possibility of potential therapeutic application of persimmon for managing cerebral ischemic and other neurodegenerative disorders. Fatemeh Forouzanfar, Shaghayegh Torabi, Vahid R. Askari, Elham Asadpour, and Hamid R. Sadeghnia Copyright © 2016 Fatemeh Forouzanfar et al. All rights reserved. In Vitro Study on Glucose Utilization Capacity of Bioactive Fractions of Houttuynia cordata in Isolated Rat Hemidiaphragm and Its Major Phytoconstituent Tue, 26 Jan 2016 13:46:59 +0000 Objective. The whole plant of Houttuynia cordata has been reported to have potent antihyperglycemic activity. Therefore, the present study was undertaken to investigate the glucose utilization capacity of bioactive fractions of ethanol extract of Houttuynia cordata (HC) in isolated rat hemidiaphragm. Methods. All the fractions, that is, aqueous (AQ), hexane (HEX), chloroform (CHL), and ethyl acetate (EA), obtained from ethanol extract of H. cordata were subjected to phytochemical standardization use in quercetin as a marker with the help of HPTLC. Further, glucose utilization capacity by rat hemidiaphragm was evaluated in 12 different sets of in vitro experiments. In the study, different fractions from H. cordata as mentioned above were evaluated, where insulin was used as standard and quercetin as a biological standard. Results. Among all the tested fractions, AQ and EA significantly increased glucose uptake by isolated rat hemidiaphragm compared to negative control. Moreover, AQ fractions enhanced the uptake of glucose significantly () and was found to be more effective than insulin. Conclusions. The augmentation in glucose uptake by hemidiaphragm in presence of AQ and EA fractions may be attributed to the presence of quercetin, which was found to be 7.1 and 3.2% w/w, respectively, in both the fractions. Manish Kumar, Satyendra K. Prasad, and Siva Hemalatha Copyright © 2016 Manish Kumar et al. All rights reserved. Effects of Curcumin on Parameters of Myocardial Oxidative Stress and of Mitochondrial Glutathione Turnover in Reoxygenation after 60 Minutes of Hypoxia in Isolated Perfused Working Guinea Pig Hearts Thu, 21 Jan 2016 08:44:00 +0000 In cardiovascular surgery ischemia-reperfusion injury is a challenging problem, which needs medical intervention. We investigated the effects of curcumin on cardiac, myocardial, and mitochondrial parameters in perfused isolated working Guinea pig hearts. After preliminary experiments to establish the model, normoxia was set at 30 minutes, hypoxia was set at 60, and subsequent reoxygenation was set at 30 minutes. Curcumin was applied in the perfusion buffer at 0.25 and 0.5 μM concentrations. Cardiac parameters measured were afterload, coronary and aortic flows, and systolic and diastolic pressure. In the myocardium histopathology and AST in the perfusate indicated cell damage after hypoxia and malondialdehyde (MDA) levels increased to 232.5% of controls during reoxygenation. Curcumin protected partially against reoxygenation injury without statistically significant differences between the two dosages. Mitochondrial MDA was also increased in reoxygenation (165% of controls), whereas glutathione was diminished (35.2%) as well as glutathione reductase (29.3%), which was significantly increased again to 62.0% by 0.05 μM curcumin. Glutathione peroxidase (GPx) was strongly increased in hypoxia and even more in reoxygenation (255% of controls). Curcumin partly counteracted this increase and attenuated GPx activity independently in hypoxia and in reoxygenation, 0.25 μM concentration to 150% and 0.5 μM concentration to 200% of normoxic activity. Ermita I. Ibrahim Ilyas, Busjra M. Nur, Sonny P. Laksono, Anton Bahtiar, Ari Estuningtyas, Caecilia Vitasyana, Dede Kusmana, Frans D. Suyatna, Muhammad Kamil Tadjudin, and Hans-Joachim Freisleben Copyright © 2016 Ermita I. Ibrahim Ilyas et al. All rights reserved. Anti-Parkinson Activity of Petroleum Ether Extract of Ficus religiosa (L.) Leaves Sun, 17 Jan 2016 16:25:38 +0000 In the present study, we evaluated anti-Parkinson’s activity of petroleum ether extract of Ficus religiosa (PEFRE) leaves in haloperidol and 6 hydroxydopamine (6-OHDA) induced experimental animal models. In this study, effects of Ficus religiosa (100, 200, and 400 mg/kg, p.o.) were studied using in vivo behavioral parameters like catalepsy, muscle rigidity, and locomotor activity and its effects on neurochemical parameters (MDA, CAT, SOD, and GSH) in rats. The experiment was designed by giving haloperidol to induce catalepsy and 6-OHDA to induce Parkinson’s disease-like symptoms. The increased cataleptic scores (induced by haloperidol) were significantly () found to be reduced, with the PEFRE at a dose of 200 and 400 mg/kg (p.o.). 6-OHDA significantly induced motor dysfunction (muscle rigidity and hypolocomotion). 6-OHDA administration showed significant increase in lipid peroxidation level and depleted superoxide dismutase, catalase, and reduced glutathione level. Daily administration of PEFRE (400 mg/kg) significantly improved motor performance and also significantly attenuated oxidative damage. Thus, the study proved that Ficus religiosa treatment significantly attenuated the motor defects and also protected the brain from oxidative stress. Jitendra O. Bhangale and Sanjeev R. Acharya Copyright © 2016 Jitendra O. Bhangale and Sanjeev R. Acharya. All rights reserved. Integrating TRPV1 Receptor Function with Capsaicin Psychophysics Thu, 14 Jan 2016 17:04:34 +0000 Capsaicin is a naturally occurring vanilloid that causes a hot, pungent sensation in the human oral cavity. This trigeminal stimulus activates TRPV1 receptors and stimulates an influx of cations into sensory cells. TRPV1 receptors function as homotetramers that also respond to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Kinase-mediated phosphorylation of TRPV1 leads to increased sensitivity to both chemical and thermal stimuli. In contrast, desensitization occurs via a calcium-dependent mechanism that results in receptor dephosphorylation. Human psychophysical studies have shown that capsaicin is detected at nanomole amounts and causes desensitization in the oral cavity. Psychophysical studies further indicate that desensitization can be temporarily reversed in the oral cavity if stimulation with capsaicin is resumed at short interstimulus intervals. Pretreatment of lingual epithelium with capsaicin modulates the perception of several primary taste qualities. Also, sweet taste stimuli may decrease the intensity of capsaicin perception in the oral cavity. In addition, capsaicin perception and hedonic responses may be modified by diet. Psychophysical studies with capsaicin are consistent with recent findings that have identified TRPV1 channel modulation by phosphorylation and interactions with membrane inositol phospholipids. Future studies will further clarify the importance of capsaicin and its receptor in human health and nutrition. Gregory Smutzer and Roni K. Devassy Copyright © 2016 Gregory Smutzer and Roni K. Devassy. All rights reserved. Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats Wed, 06 Jan 2016 14:16:16 +0000 Background. The incidence of metabolic syndrome co-existing with diabetes mellitus is on the rise globally. Objective. The present study was designed to develop a unique animal model that will mimic the pathological features seen in individuals with diabetes and metabolic syndrome, suitable for pharmacological screening of drugs. Materials and Methods. A combination of High-Fat Diet (HFD) and low dose of streptozotocin (STZ) at 30, 35, and 40 mg/kg was used to induce metabolic syndrome in the setting of diabetes mellitus in Wistar rats. Results. The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for the study to induce diabetes mellitus. Various components of metabolic syndrome such as dyslipidemia (increased triglyceride, total cholesterol, LDL cholesterol, and decreased HDL cholesterol), diabetes mellitus (blood glucose, HbA1c, serum insulin, and C-peptide), and hypertension systolic blood pressure were mimicked in the developed model of metabolic syndrome co-existing with diabetes mellitus. In addition to significant cardiac injury, atherogenic index, inflammation (hs-CRP), decline in hepatic and renal function were observed in the HF-DC group when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis, and inflammation in heart, pancreas, liver, and kidney of HF-DC group as compared to NC. Conclusion. The present study has developed a unique rodent model of metabolic syndrome, with diabetes as an essential component. Rajesh Kumar Suman, Ipseeta Ray Mohanty, Manjusha K. Borde, Ujwala Maheshwari, and Y. A. Deshmukh Copyright © 2016 Rajesh Kumar Suman et al. All rights reserved. Crude Aloe vera Gel Shows Antioxidant Propensities and Inhibits Pancreatic Lipase and Glucose Movement In Vitro Mon, 04 Jan 2016 05:39:14 +0000 Aloe vera gel (AVG) is traditionally used in the management of diabetes, obesity, and infectious diseases. The present study aimed to investigate the inhibitory potential of AVG against α-amylase, α-glucosidase, and pancreatic lipase activity in vitro. Enzyme kinetic studies using Michaelis-Menten () and Lineweaver-Burk equations were used to establish the type of inhibition. The antioxidant capacity of AVG was evaluated for its ferric reducing power, 2-diphenyl-2-picrylhydrazyl hydrate scavenging ability, nitric oxide scavenging power, and xanthine oxidase inhibitory activity. The glucose entrapment ability, antimicrobial activity, and total phenolic, flavonoid, tannin, and anthocyanin content were also determined. AVG showed a significantly higher percentage inhibition () of pancreatic lipase compared to Orlistat. AVG was found to increase the Michaelis-Menten constant and decreased the maximal velocity () of lipase, indicating mixed inhibition. AVG considerably inhibits glucose movement across dialysis tubes and was comparable to Arabic gum. AVG was ineffective against the tested microorganisms. Total phenolic and flavonoid contents were  (GAE)/mg and  (RE)/mg, respectively. AVG also showed interesting antioxidant properties. The biological activity observed in this study tends to validate some of the traditional claims of AVG as a functional food. Urmeela Taukoorah and M. Fawzi Mahomoodally Copyright © 2016 Urmeela Taukoorah and M. Fawzi Mahomoodally. All rights reserved. Enzyme Inhibitory Properties, Antioxidant Activities, and Phytochemical Profile of Three Medicinal Plants from Turkey Sun, 20 Dec 2015 15:52:17 +0000 We aimed to investigate the inhibitory potential of three medicinal plants (Hedysarum varium, Onobrychis hypargyrea, and Vicia truncatula) from Turkey against key enzymes involved in human pathologies, namely, diabetes (α-amylase and α-glucosidase), neurodegenerative disorders (tyrosinase, acetylcholinesterase, and butyrylcholinesterase), and hyperpigmentation (tyrosinase). The antioxidant potential, phenolic and flavonoid content of ethyl acetate, and methanolic and aqueous extracts were investigated using in vitro assays. The total antioxidant capacity (TAC), β-carotene/linoleic acid bleaching activity, 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH•), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+), cupric ion reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), and metal chelating activity on ferrous ions were used to evaluate the antioxidant capabilities of the extracts. The half-maximal inhibitory concentrations (IC50) of the extracts on cholinesterase, tyrosinase, and α-amylase were significantly higher than the references, galantamine, kojic acid, and acarbose, respectively. The half-maximal effective concentrations (EC50) of the extracts on TAC, CUPRAC, and FRAP were significantly higher than trolox. The phenol and flavonoid contents of the plant extracts were in the range  mg gallic acid equivalent/g extract and  mg rutin equivalent/g extract, respectively. The plants were found to possess moderate antioxidant capacities and interesting inhibitory action against key enzymes. Gokhan Zengin, Gokalp Ozmen Guler, Abdurrahman Aktumsek, Ramazan Ceylan, Carene Marie Nancy Picot, and M. Fawzi Mahomoodally Copyright © 2015 Gokhan Zengin et al. All rights reserved. Olive Mill Waste Extracts: Polyphenols Content, Antioxidant, and Antimicrobial Activities Sun, 29 Nov 2015 11:00:34 +0000 Natural polyphenols extracts have been usually associated with great bioactive properties. In this work, we investigated in vitro antioxidant and antimicrobial potential of the phenolic olive mill wastewater extracts (OWWE) and the olive cake extracts (OCE). Using the Folin Ciocalteux method, OWWE contained higher total phenol content compared to OCE ( g/L versus  mg/g). The phenolic compounds identification was carried out with a performance liquid chromatograph coupled to tandem mass spectrometry equipment (HPLC-ESI-MS). With this method, a list of polyphenols from OWWE and OCE was obtained. The antioxidant activity was measured in aqueous (DPPH) and emulsion (BCBT) systems. Using the DPPH assay, the results show that OWWE was more active than OCE and interestingly the extracts originating from mountainous areas were more active than those produced from plain areas ( μg/mL;  μg/mL, resp.). However, when the antioxidant activity was reversed in the BCBT, OCE produced from plain area was more potent than mountainous OCE. Testing by the gel diffusion assay, all the tested extracts have showed significant spectrum antibacterial activity against Staphylococcus aureus, whereas the biophenols extracts showed more limited activity against Escherichia coli and Streptococcus faecalis. Inass Leouifoudi, Hicham Harnafi, and Abdelmajid Zyad Copyright © 2015 Inass Leouifoudi et al. All rights reserved. Can Chronic Nitric Oxide Inhibition Improve Liver and Renal Dysfunction in Bile Duct Ligated Rats? Wed, 25 Nov 2015 07:20:34 +0000 The aims of the present work were to study the effects of chronic NO inhibition on liver cirrhosis and to analyze its relationship with liver and kidney damage markers. Two inhibitors of NO synthesis (inducible NO synthase (iNOS) inhibitor, aminoguanidine (AG), and nonselective NOS inhibitor, L-nitroarginine methyl ester (L-NAME)) were administered for 6 weeks to bile duct ligated (BDL) rats 3 days after surgery. The present study showed that BDL was associated with liver injury and renal impairment. BDL increased liver NO content and myeloperoxidase (MPO) activity. This was corroborated by increased oxidative stress, TNF-α, TGF-1β, and MMP-13 genes overexpression. Although both drugs reduced NO synthesis and TNF-α gene overexpression, only AG improved renal dysfunction and liver damage and reduced liver oxidative stress. However, L-NAME exacerbated liver and renal dysfunction. Both drugs failed to modulate TGF-1β and MMP-13 genes overexpression. In conclusion, inhibition of NO production by constitutive nitric oxide synthase (cNOS) plays a crucial role in liver injury and renal dysfunction while inhibition of iNOS by AG has beneficial effect. TNF-α is not the main cytokine responsible for liver injury in BDL model. Nitric oxide inhibition did not stop the progression of cholestatic liver damage. Mona Fouad Mahmoud, Sara Zakaria, and Ahmed Fahmy Copyright © 2015 Mona Fouad Mahmoud et al. All rights reserved. High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism Mon, 23 Nov 2015 16:06:54 +0000 Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R-) mediated vasodilatation. However, the effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy in postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of estrogen (0.5 mg/kg/week) for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30–300 ng/kg/min) were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined by pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF) decreased in a dose-related manner in response to Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kg−1 min−1, Ang II reduced RBF by % in estradiol-treated rats but only by % in vehicle-treated rats. Pretreatment with PD123319 blunted the response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with estradiol. We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism could potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using high-dose estrogen. Tahereh Safari, Mehdi Nematbakhsh, Roger G. Evans, and Kate M. Denton Copyright © 2015 Tahereh Safari et al. All rights reserved. Pharmacological Evaluation of Antidepressant-Like Effect of Genistein and Its Combination with Amitriptyline: An Acute and Chronic Study Sun, 22 Nov 2015 14:10:33 +0000 The present study was designed to evaluate the acute and chronic antidepressant effect of genistein in combination with amitriptyline in mice. Animals were divided into six groups () for treatment with water, genistein, or amitriptyline, either alone or in combination for ten days. Animals were subjected to locomotor activity testing; tail suspension test (TST); and forced swim test (FST) and immobility time was recorded on day one and day ten. Acute treatment of all treatment groups did not significantly reduce the immobility time (). Chronic treatment of combination of genistein (10 mg/kg) and amitriptyline (5 mg/kg and 10 mg/kg) significantly reduced the immobility time as compared to control group () and was comparable to amitriptyline alone (10 mg/kg). However, no changes in anti-immobility activity in combination of subeffective doses of genistein (5 mg/kg) and amitriptyline (5 mg/kg) were observed. Genistein at its standard dose (10 mg/kg) rendered synergistic effects in combination with subeffective dose of amitriptyline (5 mg/kg) and additive effects in combination with therapeutic dose of amitriptyline (10 mg/kg). Gaurav Gupta, Tay Jia Jia, Lim Yee Woon, Dinesh Kumar Chellappan, Mayuren Candasamy, and Kamal Dua Copyright © 2015 Gaurav Gupta et al. All rights reserved. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats Tue, 29 Sep 2015 11:05:06 +0000 Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs) is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE), AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE) and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS) complications in STZ-induced (50 mg/kg, IP) diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze), neuronal degeneration (Fluoro-Jade staining), AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde). These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications. Mohamed Naguib Zakaria, Hany M. El-Bassossy, and Waleed Barakat Copyright © 2015 Mohamed Naguib Zakaria et al. All rights reserved. Therapeutic Potential of Dietary Phenolic Acids Wed, 09 Sep 2015 07:25:35 +0000 Although modern lifestyle has eased the quality of human life, this lifestyle’s related patterns have imparted negative effects on health to acquire multiple diseases. Many synthetic drugs are invented during the last millennium but most if not all of them possess several side effects and proved to be costly. Convincing evidences have established the premise that the phytotherapeutic potential of natural compounds and need of search for novel drugs from natural sources are of high priority. Phenolic acids (PAs) are a class of secondary metabolites spread throughout the plant kingdom and generally involved in plethora of cellular processes involved in plant growth and reproduction and also produced as defense mechanism to sustain various environmental stresses. Extensive research on PAs strongly suggests that consumption of these compounds hold promise to offer protection against various ailments in humans. This paper focuses on the naturally derived PAs and summarizes the action mechanisms of these compounds during disease conditions. Based on the available information in the literature, it is suggested that use of PAs as drugs is very promising; however more research and clinical trials are necessary before these bioactive molecules can be made for treatment. Finally this review provides greater awareness of the promise that natural PAs hold for use in the disease prevention and therapy. Venkata Saibabu, Zeeshan Fatima, Luqman Ahmad Khan, and Saif Hameed Copyright © 2015 Venkata Saibabu et al. All rights reserved. Melatonin and Ischemic Stroke: Mechanistic Roles and Action Mon, 07 Sep 2015 09:30:14 +0000 Stroke is one of the most devastating neurological disabilities and brain’s vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca2+ level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke. Syed Suhail Andrabi, Suhel Parvez, and Heena Tabassum Copyright © 2015 Syed Suhail Andrabi et al. All rights reserved. Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats Thu, 03 Sep 2015 12:24:37 +0000 Background. The accompanied role of Mas receptor (MasR), bradykinin (BK), and female sex hormone on renal blood flow (RBF) response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779) and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods. Ovariectomized Wistar rats received estradiol (OVE) or vehicle (OV) for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP), RBF, and renal vascular resistance (RVR) responses to Ang 1-7 (0, 100, and 300 ng kg−1 min−1) were determined. Results. Percentage change of RBF (%RBF) in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (). Infusion of 300 ng kg−1 min−1 Ang 1-7 increased RBF by % in OVE group versus % in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly. Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats. Aghdas Dehghani, Shadan Saberi, and Mehdi Nematbakhsh Copyright © 2015 Aghdas Dehghani et al. All rights reserved. Validated HPTLC Method for Quantification of Luteolin and Apigenin in Premna mucronata Roxb., Verbenaceae Thu, 03 Sep 2015 09:26:17 +0000 A simple, rapid, and precise high-performance thin-layer chromatographic method was developed for quantitative estimation of luteolin and apigenin in Premna mucronata Roxb., family Verbenaceae. Separation was performed on silica gel 60 F254 HPTLC plates using toluene : ethyl acetate : formic acid (6 : 4 : 0.3) as mobile phase for elution of markers from extract. The determination was carried out in fluorescence mode using densitometric absorbance-reflection mode at 366 nm for both luteolin and apigenin. The methanolic extract of Premna mucronata was found to contain 10.2 mg/g % luteolin and 0.165 mg/g % of apigenin. The method was validated in terms of linearity, LOD and LOQ, accuracy, precision, and specificity. The calibration curve was found to be linear between 200 and 1000 ng/band for luteolin and 50 and 250 ng/band for apigenin. For luteolin and apigenin, the limit of detection was found to be 42.6 ng/band and 7.97 ng/band while the limit of quantitation was found to be 129.08 ng/band and 24.155 ng/band, respectively. This developed validated method is capable of quantifying and resolving luteolin and apigenin and can be applicable for routine analysis of extract and plant as a whole. Nayan G. Patel, Kalpana G. Patel, Kirti V. Patel, and Tejal R. Gandhi Copyright © 2015 Nayan G. Patel et al. All rights reserved. BF3·Et2O Catalysed 4-Aryl-3-phenyl-benzopyrones, Pro-SERMs, and Their Characterization Tue, 01 Sep 2015 13:28:55 +0000 We have synthesized the novel 4-(4-hydroxy-benzyl)-3-phenyl-chromen-2-one which is a precursor of SERMs with a smaller number of steps and good yield. Two methodologies for the synthesis have been worked out. Anhydrous BF3·Et2O catalyzed reaction was found to be selective for product formation while anhydrous AlCl3, FeCl3, and SnCl4 catalyzed ones were nonselective. Ambika Srivastava, Pooja Singh, and Rajesh Kumar Copyright © 2015 Ambika Srivastava et al. All rights reserved. Spirulina platensis Lacks Antitumor Effect against Solid Ehrlich Carcinoma in Female Mice Thu, 20 Aug 2015 12:53:11 +0000 Spirulina is a blue-green alga used as a dietary supplement. It has been shown to possess anti-inflammatory, antioxidant, and hepatoprotective properties. This study was designed to evaluate the antitumor effect of spirulina (200 and 800 mg/kg) against a murine model of solid Ehrlich carcinoma compared to a standard chemotherapeutic drug, 5-fluorouracil (20 mg/kg). Untreated mice developed a palpable solid tumor after 13 days. Unlike fluorouracil, spirulina at the investigated two dose levels failed to exert any protective effect. In addition, spirulina did not potentiate the antitumor effect of fluorouracil when they were administered concurrently. Interestingly, their combined administration resulted in a dose-dependent increase in mortality. The present study demonstrates that spirulina lacks antitumor effect against this model of solid Ehrlich carcinoma and increased mortality when combined with fluorouracil. However, the implicated mechanism is still elusive. Waleed Barakat, Shimaa M. Elshazly, and Amr A. A. Mahmoud Copyright © 2015 Waleed Barakat et al. All rights reserved. Antihyperglycemic Activity of Eucalyptus tereticornis in Insulin-Resistant Cells and a Nutritional Model of Diabetic Mice Thu, 20 Aug 2015 11:27:52 +0000 Eucalyptus tereticornis is a plant used in traditional medicine to control diabetes, but this effect has not been proved scientifically. Here, we demonstrated through in vitro assays that E. tereticornis extracts increase glucose uptake and inhibit their production in insulin-resistant C2C12 and HepG2 cells, respectively. Furthermore, in a nutritional model using diabetic mice, the administration of ethyl acetate extract of E. tereticornis reduced fasting glycaemia, improved tolerance to glucose, and reduced resistance to insulin. Likewise, this extract had anti-inflammatory effects in adipose tissue when compared to control diabetic mice. Via bioguided assays and sequential purification of the crude extract, a triterpenoid-rich fraction from ethyl acetate extracts was shown to be responsible for the biological activity. Similarly, we identified the main compound responsible for the antihyperglycemic activity in this extract. This study shows that triterpenes found in E. tereticornis extracts act as hypoglycemic/antidiabetic compounds and contribute to the understanding of their use in traditional medicine. Alis Guillén, Sergio Granados, Kevin Eduardo Rivas, Omar Estrada, Luis Fernando Echeverri, and Norman Balcázar Copyright © 2015 Alis Guillén et al. All rights reserved. Evaluation of Antidiarrheal Activity of Methanolic Extract of Maranta arundinacea Linn. Leaves Thu, 06 Aug 2015 10:53:15 +0000 Diarrhea is one of the most common causes for thousands of deaths every year. Therefore, identification of new source of antidiarrheal drugs becomes one of the most prominent focuses in modern research. Our aim was to investigate the antidiarrheal and cytotoxic activities of methanolic extract of Maranta arundinacea linn. (MEMA) leaves in rats and brine shrimp, respectively. Antidiarrheal effect was evaluated by using castor oil-induced diarrhea, enteropooling, and gastrointestinal motility tests at 200 mg/kg and 400 mg/kg body weight in rats where the cytotoxic activity was justified using brine shrimp lethality bioassay at different concentrations of MEMA. The extract showed considerable antidiarrheal effect by inhibiting 42.67% and 57.75% of diarrheal episode at the doses of 200 and 400 mg/kg, respectively. MEMA also significantly reduced the castor oil-induced intestinal volume (2.14 ± 0.16 to 1.61 ± 0.12 mL) in enteropooling test as well as intestinal transit (33.00 to 43.36%) in GI motility test, compared to their respective control. These observed effects are comparable to that of standard drug loperamide (5 mg/kg). On the other hand, in brine shrimp lethality test after 24 h, surviving brine shrimp larvae were counted and LD50 was assessed. Result showed that MEMA was potent against brine shrimp with LD50 value of 420 µg/mL. So the highest dose of 400 µg/mL of MEMA was not toxic to mice. So these results indicate that bioactive compounds are present in methanolic extract of Maranta arundinacea leaves including significant antidiarrheal activity and could be accounted for pharmacological effects. Md. Khalilur Rahman, Md. Ashraf Uddin Chowdhury, Mohammed Taufiqual Islam, Md. Anisuzzaman Chowdhury, Muhammad Erfan Uddin, and Chandra Datta Sumi Copyright © 2015 Md. Khalilur Rahman et al. All rights reserved. Comparative Effect of Lisinopril and Fosinopril in Mitigating Learning and Memory Deficit in Scopolamine-Induced Amnesic Rats Sun, 02 Aug 2015 09:04:15 +0000 Lisinopril and fosinopril were compared on scopolamine-induced learning and memory deficits in rats. A total of eighty-four male Wistar rats were divided into seven groups. Group I received 2% gum acacia orally for 4 weeks, group II received normal saline, and group III received scopolamine (2 mg/kg/ip) as single dose. Groups IV and V received lisinopril ( 0.225 mg/kg and 0.45 mg/kg), while Groups VI and VII received fosinopril (0.90 mg/kg and 1.80 mg/kg), respectively, orally for four weeks, followed by scopolamine (2 mg/kg/ip) given 45 minutes prior to experimental procedure. Evaluation of learning and memory was assessed by using passive avoidance, Morris water maze, and elevated plus maze tests followed by analysis of hippocampal morphology and quantification of the number of surviving neurons. Scopolamine induced marked impairment of memory in behavioral tests which correlated with morphological changes in hippocampus. Pretreatment with fosinopril 1.80 mg/kg was found to significantly ameliorate the memory deficits and hippocampal degeneration induced by scopolamine. Fosinopril exhibits antiamnesic activity, indicating its possible role in preventing memory deficits seen in dementia though the precise mechanism underlying this effect needs to be further evaluated. Debasree Deb, K. L. Bairy, Veena Nayak, and Mohandas Rao Copyright © 2015 Debasree Deb et al. All rights reserved. Anti-Inflammatory Effects of Heparin and Its Derivatives: A Systematic Review Tue, 12 May 2015 09:26:47 +0000 Background. Heparin, used clinically as an anticoagulant, also has anti-inflammatory properties. The purpose of this systematic review was to provide a comprehensive review regarding the efficacy and safety of heparin and its derivatives as anti-inflammatory agents. Methods. We searched the following databases up to March 2012: Pub Med, Scopus, Web of Science, Ovid, Elsevier, and Google Scholar using combination of Mesh terms. Randomized Clinical Trials (RCTs) and trials with quasi-experimental design in clinical setting published in English were included. Quality assessments of RCTs were performed using Jadad score and Consolidated Standards of Reporting Trials (CONSORT) checklist. Results. A total of 280 relevant studies were reviewed and 57 studies met the inclusion criteria. Among them 48 studies were RCTs. About 65% of articles had score of 3 and higher according to Jadad score. Twelve studies had a quality score > 40% according to CONSORT items. Asthma (), inflammatory bowel disease (), cardiopulmonary bypass (), and cataract surgery () were the most studied disease condition. Forty studies use unfractionated heparin (UFH) for intervention; the remaining studies use low molecular weight heparin (LMWH). Conclusion. Despite the conflicting results, heparin seems to be a safe and effective anti-inflammatory agent; although it is shown that heparin can decrease the level of inflammatory biomarkers and improves patient conditions, still more data from larger rigorously designed studies are needed to support use of heparin as an anti-inflammatory agent in clinical setting. However, because of the association between inflammation, atherogenesis, thrombogenesis, and cell proliferation, heparin and related compounds with pleiotropic effects may have greater therapeutic efficacy than compounds acting against a single target. Sarah Mousavi, Mandana Moradi, Tina Khorshidahmad, and Maryam Motamedi Copyright © 2015 Sarah Mousavi et al. All rights reserved. Antileishmanial Effect of 5,3′-Hydroxy-7,4′-dimethoxyflavanone of Picramnia gracilis Tul. (Picramniaceae) Fruit: In Vitro and In Vivo Studies Thu, 30 Apr 2015 17:28:05 +0000 Species of Picramnia genus are used in folk medicine to treat or prevent skin disorders, but only few species have been studied for biological activity and chemical composition. P. gracilis Tul. is a native species from Central and South America and although its fruits are edible, phytochemical analysis or medicinal uses of this species are not known. In the search of candidates to antileishmanial drugs, this work aimed to evaluate the antileishmanial activity of P. gracilis Tul. in in vitro and in vivo studies. Only ethanolic extract of fruits showed leishmanicidal activity. The majoritarian metabolite was 5,3′-hydroxy-7,4′-dimethoxyflavanone ether that exhibited high activity against L. (V.) panamensis (EC50 17.0 + 2.8 mg/mL, 53.7 μM) and low toxicity on mammalian U-937 cells, with an index of selectivity >11.8. In vivo studies showed that the flavanone administered in solution (2 mg/kg/day) or cream (2%) induces clinical improvement and no toxicity in hamsters with CL. In conclusion, this is the first report about isolation of 5,3′-hydroxy-7,4′-dimethoxyflavanone of P. gracilis Tul. The leishmanicidal activity attributed to this flavanone is also reported for the first time. Finally, the in vitro and in vivo leishmanicidal activity reported here for 5,3′-hydroxy-7,4′-dimethoxyflavanone offers a greater prospect towards antileishmanial drug discovery and development. Sara M. Robledo, Wilson Cardona, Karen Ligardo, Jéssica Henao, Natalia Arbeláez, Andrés Montoya, Fernando Alzate, Juan M. Pérez, Victor Arango, Iván D. Vélez, and Jairo Sáez Copyright © 2015 Sara M. Robledo et al. All rights reserved. Pandanus odoratissimus (Kewda): A Review on Ethnopharmacology, Phytochemistry, and Nutritional Aspects Mon, 22 Dec 2014 07:24:22 +0000 Pandanus odoratissimus Linn. (family: Pandanaceae) is traditionally recommended by the Indian Ayurvedic medicines for treatment of headache, rheumatism, spasm, cold/flu, epilepsy, wounds, boils, scabies, leucoderma, ulcers, colic, hepatitis, smallpox, leprosy, syphilis, and cancer and as a cardiotonic, antioxidant, dysuric, and aphrodisiac. It contains phytochemicals, namely, lignans and isoflavones, coumestrol, alkaloids, steroids, carbohydrates, phenolic compounds, glycosides, proteins, amino acids as well as vitamins and nutrients, and so forth. It is having immense importance in nutrition. A 100 g edible Pandanus pericarp is mainly comprised of water and carbohydrates (80 and 17 g, resp.) and protein (1.3 mg), fat (0.7 mg), and fiber (3.5 g). Pandanus fruits paste provides 321 kilocalories, protein (2.2 g), calcium (134 mg), phosphorus (108 mg), iron (5.7 mg), thiamin (0.04 mg), vitamin C (5 mg), and beta-carotene (19 to 19,000 μg) (a carotenoid that is a precursor to vitamin A). Pandanus fruit is an important source of vitamins C, B1, B2, B3, and so forth, usually prepared as a Pandanus floured drink. Traditional claims were scientifically evaluated by the various authors and the phytochemical profile of plant parts was well established. The methods for analytical estimations were developed. However, there is paucity of systematic compilation of scientifically important information about this plant. In the present review we have systematically reviewed and compiled information of pharmacognostic, ethnopharmacology, phytochemistry, pharmacology, nutritional aspects, and analytical methods. This review will enrich knowledge leading the way into the discovery of new therapeutic agents with improved and intriguing pharmacological properties. Prafulla P. Adkar and V. H. Bhaskar Copyright © 2014 Prafulla P. Adkar and V. H. Bhaskar. All rights reserved. Liver Fibrosis and Protection Mechanisms Action of Medicinal Plants Targeting Apoptosis of Hepatocytes and Hepatic Stellate Cells Thu, 20 Nov 2014 07:49:00 +0000 Following chronic liver injury, hepatocytes undergo apoptosis leading to activation of hepatic stellate cells (HSC). Consequently, activated HSC proliferate and produce excessive extracellular matrix, responsible for the scar formation. The pandemic trend of obesity, combined with the high incidence of alcohol intake and viral hepatitis infections, highlights the urgent need to find accessible antifibrotic therapies. Treatment strategies should take into account the versatility of its pathogenesis and act on all the cell lines involved to reduce liver fibrosis. Medicinal plants are achieving popularity as antifibrotic agents, supported by their safety, cost-effectiveness, and versatility. This review will describe the role of hepatocytes and HSC in the pathogenesis of liver fibrosis and detail the mechanisms of modulation of apoptosis of both cell lines by twelve known hepatoprotective plants in order to reduce liver fibrosis. Florent Duval, Jorge E. Moreno-Cuevas, Maria Teresa González-Garza, Carlos Rodríguez-Montalvo, and Delia Elva Cruz-Vega Copyright © 2014 Florent Duval et al. All rights reserved. Comparative Evaluation of Cytotoxic and Apoptogenic Effects of Several Coumarins on Human Cancer Cell Lines: Osthole Induces Apoptosis in p53-Deficient H1299 Cells Wed, 03 Sep 2014 09:24:59 +0000 Natural products are excellent resources for finding lead structures for the development of chemotherapeutic agents. Coumarins are a class of natural compounds found in a variety of plants. In this study, we evaluated the cytotoxic potential of coumarins isolated from Prangos ferulacea (L.) Lindl. in PC3, SKNMC, and H1299 (p53 null) human carcinoma cell lines. Osthole proved to be an outstanding potent cytotoxic agent especially against PC3 cells. Isoimperatorin exhibited moderate inhibitory effect against SKNMC and PC3 cell lines. Oxypeucedanin and braylin did not display any cytotoxic activity. In the next set of experiments, the apoptotic potentials of osthole and isoimperatorin were investigated. Induction of apoptosis by isoimperatorin was accompanied by an increase in activation of caspase-3, -8, and -9 in SKNMC cells and caspase-3 and -9 in PC3 cells. Moreover, isoimperatorin induced apoptosis by upregulating Bax and Smac/DIABLO genes in PC3 and SKNMC cells. Osthole induced apoptosis by downregulating antiapoptotic Bcl-2 in only PC3 cells and upregulating the proapoptotic genes Bax and Smac/DIABLO in PC3, SKNMC, and H1299 cells. The effects of osthole on H1299 cells are important because the loss of p53 has been associated with poor clinical prognosis in cancer treatment. Yalda Shokoohinia, Leila Hosseinzadeh, Maryam Alipour, Ali Mostafaie, and Hamid-Reza Mohammadi-Motlagh Copyright © 2014 Yalda Shokoohinia et al. All rights reserved.