Advances in Pharmacological Sciences The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Changes in IL-2 and IL-10 during Chronic Administration of Isoniazid, Nevirapine, and Paracetamol in Rats Sun, 20 Nov 2016 13:56:17 +0000 The aim of this study was to illustrate the initial subclinical drug-induced liver injury and the associated adaptive immune response by monitoring for the changes in plasma IL-2, IL-10, and some cytochrome P450 activity during chronic administration of nevirapine (NVP), isoniazid (INH), and paracetamol (PAR) in rats without clinical hepatotoxicity. Male Sprague-Dawley (SD) rats were divided into four groups (saline (S), NVP, INH, and PAR) of 25 animals each. The drugs were administered daily for 42 days at therapeutic doses (NVP 200 mg/kg, PAR 500 mg/kg, and INH 20 mg/kg) to the respective groups by oral gavage and five rats per group were sacrificed weekly. All the three drugs induced a subclinical liver injury in the first 2-3 weeks followed by healing, indicating adaption. The liver injury was pathologically similar and was associated with immune stimulation and increased cytochrome P450 activity. NVP- and PAR-induced liver injury lasted up to 14 days while that for INH lasted for 28 days. NVP-induced liver injury was associated with increased IL-2, CD4 count, and CYP3A2 activity, followed by increased IL-10 during the healing phase. In conclusion, the initial drug-induced subclinical liver injury, its spontaneous healing, and the associated adaptive immune response have been demonstrated. Zanelle Bekker, Andrew Walubo, and Jan B. Du Plessis Copyright © 2016 Zanelle Bekker et al. All rights reserved. The Methanolic Extract from Murraya koenigii L. Inhibits Glutamate-Induced Pain and Involves ATP-Sensitive K+ Channel as Antinociceptive Mechanism Wed, 12 Oct 2016 08:53:17 +0000 Murraya koenigii L. is a perennial shrub, belonging to the family Rutaceae. Traditionally, the leaves of this plant are extensively used in treatment of a wide range of diseases and disorders including pain and inflammation. Although researchers have revealed the antinociceptive effects of this plant’s leaves during past few years, the mechanisms underlying these effects are still unknown. Therefore, the present study evaluated some antinociceptive mechanisms of the methanolic extract of M. koenigii (MEMK) leaves along with its antinociceptive potential using several animal models. The antinociceptive effects of MEMK were evaluated using formalin-induced licking and acetic acid-induced writhing tests at the doses of 50, 100, and 200 mg/kg. In addition, we also justified the possible participations of glutamatergic system and ATP-sensitive potassium channels in the observed activities. Our results demonstrated that MEMK significantly () inhibited the pain thresholds induced by formalin and acetic acid in a dose-dependent manner. MEMK also significantly () suppressed glutamate-induced pain. Moreover, pretreatment with glibenclamide (an ATP-sensitive potassium channel blocker) at 10 mg/kg significantly () reversed the MEMK-mediated antinociception. These revealed that MEMK might have the potential to interact with glutamatergic system and the ATP-sensitive potassium channels to exhibit its antinociceptive activities. Therefore, our results strongly support the antinociceptive effects of M. koenigii leaves and provide scientific basis of their analgesic uses in the traditional medicine. Nushrat Sharmin Ani, Sudip Chakraborty, and Md. Moniruzzaman Copyright © 2016 Nushrat Sharmin Ani et al. All rights reserved. Thrombus Degradation by Fibrinolytic Enzyme of Stenotrophomonas sp. Originated from Indonesian Soybean-Based Fermented Food on Wistar Rats Sun, 21 Aug 2016 11:00:06 +0000 Objective. To evaluate thrombus degrading effect of a fibrinolytic enzyme from food origin Stenotrophomonas sp. of Indonesia. Methods. Prior to animal study, the enzyme safety was tested using cell culture. The effect on expression of tissue plasminogen activator was also analysed in the cell culture. For in vivo studies, 25 Wistar rats were used: normal control, negative control, treatment groups with crude and semipurified enzyme given orally at 25 mg/kg, and positive control group which received Lumbrokinase at 25 mg/kg. Blood clot in the tail was induced by kappa carrageenan injection at 1 mg/kg BW. Results. Experiment with cell culture confirmed the enzyme safety at the concentration used and increased expression of tPA. Decreasing of thrombus was observed in the positive group down to 70.35 ± 23.11% of the negative control animals (100%). The thrombus observed in the crude enzyme treatment was down to 56.99 ± 15.95% and 71.5 ± 15.7% for semipurified enzyme. Scanning electron microscopy showed clearly that bood clots were found in the animals injected with kappa carrageenan; however, in the treatment and positive groups, the clot was much reduced. Conclusions. Oral treatment of enzyme from Stenotrophomonas sp. of Indonesian fermented food was capable of degrading thrombus induced in Wistar rats. Florensia Nailufar, Raymond R. Tjandrawinata, and Maggy T. Suhartono Copyright © 2016 Florensia Nailufar et al. All rights reserved. Pharmacological Evaluation of Naproxen Metal Complexes on Antinociceptive, Anxiolytic, CNS Depressant, and Hypoglycemic Properties Mon, 11 Jul 2016 14:08:07 +0000 Purpose. The present study was designed to investigate the antinociceptive, anxiolytic, CNS depressant, and hypoglycemic effects of the naproxen metal complexes. Methods. The antinociceptive activity was evaluated by acetic acid-induced writhing method and radiant heat tail-flick method while anxiolytic activity was evaluated by elevated plus maze model. The CNS depressant activity of naproxen metal complexes was assessed using phenobarbitone-induced sleeping time test and the hypoglycemic test was performed using oral glucose tolerance test. Results. Metal complexes significantly () reduced the number of abdominal muscle contractions induced by 0.7% acetic acid solution in a dose dependent manner. At the dose of 25 mg/kg body weight p.o. copper, cobalt, and zinc complexes exhibited higher antinociceptive activity having 59.15%, 60.56%, and 57.75% of writhing inhibition, respectively, than the parent ligand naproxen (54.93%). In tail-flick test, at both doses of 25 and 50 mg/kg, the copper, cobalt, silver, and zinc complexes showed higher antinociceptive activity after 90 minutes than the parent drug naproxen. In elevated plus maze (EPM) model the cobalt and zinc complexes of naproxen showed significant anxiolytic effects in dose dependent manner, while the copper, cobalt, and zinc complexes showed significant CNS depressant and hypoglycemic activity. Conclusion. The present study demonstrated that copper, cobalt, and zinc complexes possess higher antinociceptive, anxiolytic, CNS depressant, and hypoglycemic properties than the parent ligand. Md. Sharif Hasan, Narhari Das, Zobaer Al Mahmud, and S. M. Abdur Rahman Copyright © 2016 Md. Sharif Hasan et al. All rights reserved. MDMA Impairs Response to Water Intake in Healthy Volunteers Tue, 14 Jun 2016 06:18:44 +0000 Hyponatremia is a serious complication of 3,4-methylenedioxymethamphetamine (MDMA) use. We investigated potential mechanisms in two double-blind, placebo-controlled studies. In Study 1, healthy drug-experienced volunteers received MDMA or placebo alone and in combination with the alpha-1 adrenergic inverse agonist prazosin, used as a positive control to release antidiuretic hormone (ADH). In Study 2, volunteers received MDMA or placebo followed by standardized water intake. MDMA lowered serum sodium but did not increase ADH or copeptin, although the control prazosin did increase ADH. Water loading reduced serum sodium more after MDMA than after placebo. There was a trend for women to have lower baseline serum sodium than men, but there were no significant interactions with drug condition. Combining studies, MDMA potentiated the ability of water to lower serum sodium. Thus, hyponatremia appears to be a significant risk when hypotonic fluids are consumed during MDMA use. Clinical trials and events where MDMA use is common should anticipate and mitigate this risk. Matthew J. Baggott, Kathleen J. Garrison, Jeremy R. Coyle, Gantt P. Galloway, Allan J. Barnes, Marilyn A. Huestis, and John E. Mendelson Copyright © 2016 Matthew J. Baggott et al. All rights reserved. A Review on Medicinal Properties of Orientin Thu, 19 May 2016 16:29:54 +0000 Medicinal plants continue to play an important role in modern medications and healthcare as consumers generally believe that most of them cause fewer or milder adverse effects than the conventional modern medicines. In order to use the plants as a source of medicinal agents, the bioactive compounds are usually extracted from plants. Therefore, the extraction of bioactive compounds from medicinal plants is a crucial step in producing plant-derived drugs. One of the bioactive compounds isolable from medicinal plants, orientin, is often used in various bioactivity studies due to its extensive beneficial properties. The extraction of orientin in different medicinal plants and its medicinal properties, which include antioxidant, antiaging, antiviral, antibacterial, anti-inflammation, vasodilatation and cardioprotective, radiation protective, neuroprotective, antidepressant-like, antiadipogenesis, and antinociceptive effects, are discussed in detail in this review. Kit Ying Lam, Anna Pick Kiong Ling, Rhun Yian Koh, Ying Pei Wong, and Yee How Say Copyright © 2016 Kit Ying Lam et al. All rights reserved. Radical-Scavenging Activity and Ferric Reducing Ability of Juniperus thurifera (L.), J. oxycedrus (L.), J. phoenicea (L.) and Tetraclinis articulata (L.) Mon, 16 May 2016 10:44:39 +0000 Objective. The aim of this work is to study and compare the antioxidant properties and phenolic contents of aqueous leaf extracts of Juniperus thurifera, Juniperus oxycedrus, Juniperus Phoenicea, and Tetraclinis articulata from Morocco. Methods. Antioxidant activities of the extracts were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging ability, Trolox equivalent antioxidant capacity (TEAC), and ferric reducing antioxidant power (FRAP) assays. Also the total phenolic and flavonoids contents of the extracts were determined spectrophotometrically. Results. All the extracts showed interesting antioxidant activities compared to the standard antioxidants (butylated hydroxytoluene (BHT), quercetin, and Trolox). The aqueous extract of Juniperus oxycedrus showed the highest antioxidant activity as measured by DPPH, TEAC, and FRAP assays with IC50 values of  μg/mL,  μg/mL, and  μg/mL, respectively. The strong correlation observed between antioxidant capacities and their total phenolic contents indicated that phenolic compounds were a major contributor to antioxidant properties of these plants extracts. Conclusion. These results suggest that the aqueous extracts of Juniperus thurifera, Juniperus oxycedrus, Juniperus phoenicea, and Tetraclinis articulata can constitute a promising new source of natural compounds with antioxidants ability. Meryem El Jemli, Rabie Kamal, Ilias Marmouzi, Asmae Zerrouki, Yahia Cherrah, and Katim Alaoui Copyright © 2016 Meryem El Jemli et al. All rights reserved. Review of Anti-Inflammatory Herbal Medicines Tue, 10 May 2016 09:53:21 +0000 Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, evening primrose, and Devil’s claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle. Mona Ghasemian, Sina Owlia, and Mohammad Bagher Owlia Copyright © 2016 Mona Ghasemian et al. All rights reserved. Cytotoxicity and Antiproliferative Activity Assay of Clove Mistletoe (Dendrophthoe pentandra (L.) Miq.) Leaves Extracts Wed, 23 Mar 2016 14:13:43 +0000 Clove mistletoe (Dendrophthoe pentandra (L.) Miq.) is a semiparasitic plant that belongs to Loranthaceae family. Clove mistletoe was traditionally used for cancer treatment in Indonesia. In the present study, we examined cytotoxicity of clove mistletoe leaves extracts against brine shrimps and conducted their antiproliferative activity on K562 (human chronic myelogenous leukemia) and MCM-B2 (canine benign mixed mammary) cancer cell lines in vitro. The tested samples were water extract, ethanol extract, ethanol fraction, ethyl acetate fraction, and n-hexane fraction. Cytotoxicity was screened using Brine Shrimp Lethality Test (BSLT). Antiproliferative activity was conducted using Trypan Blue Dye Method and cells were counted using haemocytometer. The results showed that n-hexane fraction exhibited significant cytotoxicity with LC50 value of 55.31 μg/mL. The n-hexane fraction was then considered for further examination. The n-hexane fraction of clove mistletoe could inhibit growth of K562 and MCM-B2 cancer cell lines in vitro. The inhibition activity of clove mistletoe n-hexane fraction at concentration of 125 μg/mL on K562 cancer cell lines was 38.69%, while on MCM-B2 it was 41.5%. Therefore, it was suggested that clove mistletoe had potential natural anticancer activity. Vida Elsyana, Maria Bintang, and Bambang Pontjo Priosoeryanto Copyright © 2016 Vida Elsyana et al. All rights reserved. The Influence of Palatable Diets in Reward System Activation: A Mini Review Sun, 20 Mar 2016 11:37:49 +0000 The changes in eating patterns that have occurred in recent decades are an important cause of obesity. Food intake and energy expenditure are controlled by a complex neural system involving the hypothalamic centers and peripheral satiety system (gastrointestinal and pancreatic hormones). Highly palatable and caloric food disrupts appetite regulation; however, palatable foods induce pleasure and reward. The cafeteria diet is such a palatable diet and has been shown consistently to increase body weight and induce hyperplasia in animal obesity models. Moreover, palatable high-fat foods (such as those of the cafeteria diet) can induce addiction-like deficits in brain reward function and are considered to be an important source of motivation that might drive overeating and contribute to the development of obesity. The mechanism of neural adaptation triggered by palatable foods is similar to those that have been reported for nondrug addictions and long-term drug use. Thus, this review attempts to describe the potential mechanisms that might lead to highly palatable diets, such as the cafeteria diet, triggering addiction, or compulsion through the reward system. Isabel Cristina de Macedo, Joice Soares de Freitas, and Iraci Lucena da Silva Torres Copyright © 2016 Isabel Cristina de Macedo et al. All rights reserved. Gender Difference in Renal Blood Flow Response to Angiotensin II Administration after Ischemia/Reperfusion in Rats: The Role of AT2 Receptor Thu, 10 Mar 2016 13:00:47 +0000 Background. Renal ischemia/reperfusion (I/R) is one of the major causes of kidney failure, and it may interact with renin angiotensin system while angiotensin II (Ang II) type 2 receptor (AT2R) expression is gender dependent. We examined the role of AT2R blockade on vascular response to Ang II after I/R in rats. Methods. Male and female rats were subjected to 30 min renal ischemia followed by reperfusion. Two groups of rats received either vehicle or AT2R antagonist, PD123319. Mean arterial pressure (MAP), and renal blood flow (RBF) responses were assessed during graded Ang II (100, 300, and 1000 ng/kg/min, i.v.) infusion at controlled renal perfusion pressure (RPP). Results. Vehicle or antagonist did not alter MAP, RPP, and RBF levels significantly; however, 30 min after reperfusion, RBF decreased insignificantly in female treated with PD123319 (). Ang II reduced RBF and increased renal vascular resistance (RVR) in a dose-related fashion (), and PD123319 intensified the reduction of RBF response in female (), but not in male rats. Conclusion. The impact of the AT2R on vascular responses to Ang II in renal I/R injury appears to be sexually dimorphic. PD123319 infusion promotes these hemodynamic responses in female more than in male rats. Maryam Maleki and Mehdi Nematbakhsh Copyright © 2016 Maryam Maleki and Mehdi Nematbakhsh. All rights reserved. Pharmacokinetics of Immediate and Sustained Release Cephalexin Administered by Different Routes to Llamas (Lama glama) Wed, 09 Mar 2016 08:16:48 +0000 We investigate the pharmacokinetics of two different cephalexin formulations administered to llamas by the intravenous (IV), intramuscular (IM), and subcutaneous (SC) routes, the minimum inhibitory concentration (MIC) of cephalexin against some Escherichia coli and staphylococci isolated from llamas, and we apply the PK/PD modelling approach, so that effective dosage recommendations for this species could be made. Six llamas received immediate (10 mg/kg, IV, IM, and SC) and sustained (8 mg/kg IM, SC) release cephalexin. Pharmacokinetic parameters were calculated by noncompartmental approach. Immediate release SC administration produced a significantly longer elimination half-life as compared with the IV and IM administration ( versus and  h, resp.) and higher mean absorption time as compared with the IM administration ( versus  h). Absolute bioavailability was in the range of 72–89% for both formulations and routes of administration. Cephalexin MIC90 values against staphylococci and E. coli were 1.0 and 8.0 μg/mL, respectively. Our results show that the immediate release formulation (10 mg/kg) would be effective for treating staphylococcal infections administered every 8 h (IM) or 12 h (SC), whereas the sustained release formulation (8 mg/kg) would require the IM or SC administration every 12 or 24 h, respectively. Verónica Kreil, Luis Ambros, Ana Paula Prados, Lisa Tarragona, Agustina Monfrinotti, Guillermo Bramuglia, and Marcela Rebuelto Copyright © 2016 Verónica Kreil et al. All rights reserved. Protective Role of Ramipril and Candesartan against Myocardial Ischemic Reperfusion Injury: A Biochemical and Transmission Electron Microscopical Study Sun, 06 Mar 2016 13:35:03 +0000 The present study was designed to investigate the role of combined administration of Ramipril and Candesartan against in vitro myocardial ischemic reperfusion injury in rat. Male Wistar albino rats were divided into five groups () and treated with saline (10 mL/kg), Ramipril (2 mg/kg), Candesartan (1 mg/kg), and the combination of both drugs, respectively 24 h before induction of global ischemia (5 min of stabilization, 9 min of global ischemia, and 12 min of reflow). Combination of Ramipril and Candesartan when compared to the monotherapy significantly increased the levels of superoxide dismutase, reduced glutathione, catalase, and nitric oxide and decreased the levels of thiobarbituric acid reactive substances. In addition, the superior protective role of combination of Ramipril and Candesartan on ischemia induced myocardial damage was further confirmed by well preserved myocardial tissue architecture in light microscopy and transmission electron microscopy analysis studies. The combination was proved to be effective in salvaging the myocardial tissue against ischemic reperfusion injury when compared to the monotherapy of individual drugs and further investigations on protective mechanism of drugs by increasing the nitric oxide level at molecular levels are needed. Mohamed Saleem Thattakudian Sheik Uduman, Rajitha Bodd Reddy, Priyanka Punuru, Gopinath Chakka, and Gauthaman Karunakaran Copyright © 2016 Mohamed Saleem Thattakudian Sheik Uduman et al. All rights reserved. Cytotoxic Activity of Holothuria leucospilota Extract against Leishmania infantum In Vitro Sun, 28 Feb 2016 11:15:18 +0000 Leishmaniasis is a tropical parasitic infection. The resistance and toxicity issues are the major complications and remain significant consequences related to the treatment of leishmaniasis with the recent and classical drugs. Thus there is an immediate requirement to develop new compounds for the treatment of this protozoan disease. Sea cucumbers or holothurians are potentially presented as the marine sources of antimicrobial and cytotoxic compounds. The aim of this study was investigation of in vitro antileishmanial activity of methanol extract of body wall, coelomic fluid, and cuvierian organs of Holothuria leucospilota obtained from coastal parts of Persian Gulf against Leishmania infantum promastigotes and axenic amastigotes. The colorimetric MTT assay was used to determine L. infantum promastigotes and axenic amastigotes viability at different concentrations of the extracts and drug control (Glucantime®) at time dependent manner and the results are represented as IC50 (50% of inhibitory concentration). Coelomic fluid was the most active extract among the three different extracts of H. leucospilota against L. infantum promastigotes and axenic amastigotes with IC50s of 62.33 μg/mL and 22.4 μg/mL and 73 μg/mL and 46 μg/mL at 48 and 72 hours after treatment, respectively. Cuvierian organs extract showed less toxicity with IC50s more than 1000 μg/mL for both Leishmania infantum axenic amastigotes and promastigotes forms after 48 and 72 hours of exposure. Results acquired from the present study propose that the sea cucumber H. leucospilota may be a provoking source of antileishmanial compounds and could be a lead source in the development of the potent antileishmanial and cytotoxic drugs. Shahram Khademvatan, Alborz Eskandari, Jasem Saki, and Masoud Foroutan-Rad Copyright © 2016 Shahram Khademvatan et al. All rights reserved. Potential Effects of Silymarin and Its Flavonolignan Components in Patients with β-Thalassemia Major: A Comprehensive Review in 2015 Sun, 21 Feb 2016 14:20:31 +0000 Major β-thalassemia (β-TM) is one of the most common inherited hemolytic types of anemia which is caused as a result of absent or reduced synthesis of β-globin chains of hemoglobin. This defect results in red blood cells lysis and chronic anemia that can be treated by multiple blood transfusions and iron chelation therapy. Without iron chelation therapy, iron overload will cause lots of complications in patients. Antioxidant components play an important role in the treatment of the disease. Silymarin is an antioxidant flavonoid isolated from Silybum marianum plant. In the present study, we reviewed clinical and experimental studies investigating the use of silymarin prior to September 1, 2015, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases and we evaluated the potential effects of silymarin on controlling the complications induced by iron overload in patients with β-TM. Based on the results of the present study, we can conclude that silymarin may be useful as an adjuvant for improving multiple organ dysfunctions. Hadi Darvishi Khezri, Ebrahim Salehifar, Mehrnoush Kosaryan, Aily Aliasgharian, Hossein Jalali, and Arash Hadian Amree Copyright © 2016 Hadi Darvishi Khezri et al. All rights reserved. Drug Efflux Transporters Are Overexpressed in Short-Term Tamoxifen-Induced MCF7 Breast Cancer Cells Sun, 14 Feb 2016 14:15:14 +0000 Tamoxifen is the first line drug used in the treatment of estrogen receptor-positive (ER+) breast cancer. The development of multidrug resistance (MDR) to tamoxifen remains a major challenge in the treatment of cancer. One of the mechanisms related to MDR is decrease of drug influx via overexpression of drug efflux transporters such as P-glycoprotein (P-gp/MDR1), multidrug resistance associated protein (MRP), or BCRP (breast cancer resistance protein). We aimed to investigate whether the sensitivity of tamoxifen to the cells is maintained through the short period and whether the expressions of several drug efflux transporters have been upregulated. We exposed MCF7 breast cancer cells with tamoxifen 1 μM for 10 passages (MCF7 (T)). The result showed that MCF7 began to lose their sensitivity to tamoxifen from the second passage. MCF7 (T) also showed a significant increase in all transporters examined compared with MCF7 parent cells. The result also showed a significant increase of CC50 in MCF7 (T) compared to that in MCF7 (97.54 μM and 3.04 μM, resp.). In conclusion, we suggest that the expression of several drug efflux transporters such as P-glycoprotein, MRP2, and BCRP might be used and further studied as a marker in the development of tamoxifen resistance. Desak Gede Budi Krisnamurti, Melva Louisa, Erlia Anggraeni, and Septelia Inawati Wanandi Copyright © 2016 Desak Gede Budi Krisnamurti et al. 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.