Pharmacophore Modeling and Molecular Docking Studies on Pinus roxburghii as a Target for Diabetes Mellitus.

The present study attempts to establish a relationship between ethnopharmacological claims and bioactive constituents present in Pinus roxburghii against all possible targets for diabetes through molecular docking and to develop a pharmacophore model for the active target. The process of molecular docking involves study of different bonding modes of one ligand with active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP-1ß), dipeptidyl peptidase-IV (DPP-IV), aldose reductase (AR), and insulin receptor (IR) with help of docking software Molegro virtual docker (MVD). From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR. Then, LigandScout was applied to develop a pharmacophore model for active target. LigandScout revealed that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major requirement of the pharmacophore generated. In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore. The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications.

Analgesic and Anti-Inflammatory Activity of Pinus roxburghii Sarg.

The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae) is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100 mg/kg, 300 mg/kg, and 500 mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models.

Gastroprotective effect of Achyranthes aspera Linn. leaf on rats.

OBJECTIVE: The study was aimed at evaluating the antiulcer activity of ethanolic extract of Achyranthes aspera (EEAA) leaf. METHODS: The anti-ulcer assays were performed on pylorus ligation and chronic ethanol induced ulcer model. The effects of the EEAA on gastric content volume, pH, free acidity, total acidity and ulcer index were evaluated. RESULTS: The percentage of ulcer protection (59.55% and 35.58%) was significantly (P < 0.001) higher in the groups treated with the high dose of EEAA (600 mg/kg), it also reduced the volume of gastric juice and total acidity whereas, gastric pH was increased significantly. CONCLUSIONS: The results of this study show significant gastroprotective activity of EEAA may be due to presence of phyto-constituents like flavanoids, saponins and tannins.

Formulation and evaluation of famotidine floating tablets.

The purpose of this investigation was to prepare a gastroretentive drug delivery system of famotidine. Floating tablets of famotidine were prepared employing two different grades of methocel K100 and methocel K15M by effervescent technique; these grades of methocel were evaluated for their gel forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, in vitro buoyancy and dissolution studies. The effect of citric acid on drug release profile and floating properties was investigated. The prepared tablets exhibited satisfactory physico-chemical characteristics. All the prepared batches showed good in vitro buoyancy. The tablet swelled radially and axially during in vitro buoyancy studies. It was observed that the tablet remained buoyant for 6-10 hours. Decrease in the citric acid level increased the floating lag time but tablets floated for longer duration. A combination of sodium bicarbonate (130mg) and citric acid (10mg) was found to achieve optimum in vitro buoyancy. The tablets with methocel K100 were found to float for longer duration as compared with formulations containing methocel K15M. The drug release from the tablets was sufficiently sustained and non-Fickian transport of the drug from tablets was confirmed.

Metabolic enzyme considerations in cancer therapy.

The clinical application of new antineoplastic drugs has been limited because of low therapeutic index and lack of efficacy in humans. Thus, improvement in efficacy of old and new anticancer drugs has been attempted by manipulating their pharmacokinetic properties. Four inter-related factors, which determine the pharmacokinetic behavior of a drug include absorption, distribution, metabolism and excretion. The drug-metabolizing enzymes have been classified in two major groups: phase I and phase II enzymes. Phase I enzymes comprise the oxidases, dehydrogenases, deaminases, hydrolases. Phase II enzymes include primarily UDP-glucuronosyltransferases (UGTs), glutathionetransferases (GSTs), sulfotransferases (SULTs), N-acetyl transferases (NATs), methyltransferases and aminoacid transferases that conjugate products of phase I reactions and parent compounds with appropriate functional groups to generate more water soluble compounds which are more readily eliminated. The importance of these enzymes in the metabolism of specific drugs varies according to the chemical nature of the drug, Drug metabolism is modulated by factors that change among species and even among individuals in a population. Such factors can be environmental or genetic in origin, and influence how a drug is metabolized and to what extent. An awareness of these variables is invaluable when the safety and efficacy of new anticancer drugs are evaluated (1).

Psychopharmacological profile of hydro-alcoholic extract of Euphorbia neriifolia leaves in mice and rats.

The leaf extract of E. neriifolia significantly reduced apomorphine-induced stereotypy in mice at all doses (100, 200, 400 mg/kg body weight) in mice and rats and was devoid of catalepsic effect thereby, suggesting specific dopaminergic receptor modulating activity. The extract (400 mg/kg) potentiated pentobarbitone-induced hypnosis. It showed protection against maximal electro-shock-induced convulsion at 400 mg/kg. E. neriifolia leaf extract had anxiolytic action at 400 mg/kg by increasing the percentage of time spent in open arm in elevated plus-maze. The extract did not reverse scopolamine-induced amnesia on elevated plus-maze. It increased transfer latency at 200 and 400 mg/kg and also in combination with scopolamine. These results indicated anti-anxiety, anti-psychotic and anti-convulsant activity of E. neriifolia leaf extract in mice and rats. Phytochemical study showed the presence of steroidal saponin, reducing sugar, tannins, flavonoids in the crude leaf extract

Effect of Calotropis procera latex on isoproterenol induced myocardial infarction in albino rats.

The alcoholic extract of the latex obtained from Calotropis procera (Asclepidaceae) was evaluated for protection against isoproterenol (20 mg/100 g body wt., s.c.)-induced myocardial infarction in albino rats. The heart damage induced by isoproterenol was indicated by elevated levels of the marker enzymes such as Creatine Kinase-isoenzyme (CK-MB), Lactate dehydrogenase (LDH), Serum Glutamate Oxaloacetic Transaminase (SGOT) and Serum Glutamate Pyruvate Transaminase (SGPT) in serum with increased lipid peroxide and reduced glutathione content in heart homogenates. Microscopical examination (histopathology) was also performed on the myocardial tissue. Pretreatment with an ethanolic latex extract of Calotropis procera at a dose of 300 mg/kg body wt., administered orally thrice a day for 30 days, reduced significantly (p < 0.01) the elevated marker enzyme levels in serum and heart homogenates in isoproterenol-induced myocardial infarction. Histopathological observation revealed a marked protection by the extract in myocardial necrotic damage.

Pro-healing effect of Cinnamomum zeylanicum bark.

The ethanol extract of the bark of Cinnamomum zeylanicum was evaluated for wound healing activity in Wistar rats. The extract was administered by the oral route at a dose of 250 mg/kg and 500 mg/kg body weight (1/8 and 1/4 of LD(50), respectively) for all the wound models selected, excision, incision and dead space wounds. The extract significantly enhanced the wound breaking strength in the case of incision wound, the rate of wound contraction and the period of epithelization in the case of excision wound. The granulation tissue weight, its breaking strength and its hydroxyproline content was also increased by the extract in the dead space wound.

Internet--implications for the future of phytopharmacological research.

Modern information technologies and world wide communications through the Internet play a significant role in medicinal plant research across the globe. The phenomenal growth in Internet usage is largely due to the success of World Wide Web. Various useful websites and databases on phytopharmacology are already in the "Net" and many more are being added constantly. The future of phytopharmacological research is handling the existing information in proper way. In this review of the Internet, compilation of important websites is expected to stimulate, instruct and update academicians and researchers involved in phytopharmacological research.

Preliminary study on antifertility activity of Calotropis procera roots in female rats.

The effect of ethanolic extract of the roots of Calotropis procera has been studied in albino rats to explore its antifertility and hormonal activities. A strong antiimplantation (inhibition 100%) and uterotropic activity was observed at the dose level of 250 mg/kg (1/4 of LD(50)). No antiestrogenic activity could be detected.

Self-assembled carbohydrate-stabilized ceramic nanoparticles for the parenteral delivery of insulin.

The insulin-bearing aquasomes were fabricated by first preparing the nanosize calcium phosphate dihydrate core. The calcium phosphate dihydrate core was prepared by colloidal precipitation and sonication of disodium hydrogen phosphate solution and calcium chloride solution at low temperature. This core was coated with cellobiose, pyridoxal-5-phosphate, or trehalose under sonication and was further loaded with the drug at low temperature by a partial adsorption mechanism. The prepared systems were characterized for size, shape, size distribution, drug loading efficiency, and in vivo performance. The in vivo performance of the formulated aquasome was compared with standard porcine insulin solution, and better results were observed compared to insulin solution.

Brain drug delivery system bearing dopamine hydrochloride for effective management of parkinsonism.

Dopamine hydrochloride bearing positively charged small liposomes was prepared by sonicating the multilamellar vesicles. These vesicles were characterized for their physical attributes (shape, size, charge, drug entrapment efficiency, and drug leakage). The drug release kinetics from the liposomes were also studied and found to be Fickian-type diffusion. In vivo performance of the drug-entrapped liposomes was assessed by periodic measurement of drug- (chlorpromazine) induced catatonia in Sprague-Dowley rats. These results were compared with the plain dopamine HCl and levodopa preparations as well with the marketed formulation of levodopa containing carbidopa (Syndopa). These studies revealed that the dopamine can be effectively delivered to the brain by incorporating it into liposomes, and its degradation in circulation can also be protected. The results of liposomal formulation were found to be superior compared to plain levodopa as well as Syndopa.

Hepatoprotective effects of Andrographis paniculata against carbon tetrachloride-induced liver damage.

Alcoholic extract of the leaves of Andrographis paniculata Ness (= AAP) was obtained by cold maceration. A dose of 300 mg/kg (1/6 of LD50) of the extract was selected to study hepatoprotective action against carbon tetrachloride-induced liver damage. The extract was found to be effective in preventing liver damage which was evident by morphological, biochemical and functional parameters.

Hepatoprotective effect of Vitex negundo against carbon tetrachloride-induced liver damage.

Alcoholic extract of the seeds of Vitex negundo Linn. was obtained by cold maceration. A dose of 250 mg/kg (1/6 of LD50) of the extract was selected to study the hepatoprotective action against carbon tetrachloride-induced liver damage. The extract was found to be effective in preventing liver damage which was evident by morphological, biochemical and functional parameters.