Amir Badshah

The morphology, extractions, chemical constituents and uses of Terminalia chebula: A review

Trust on traditional medicines in the treatment of ailment is at a halt and a lot of population, especially rural population, still believes on herbs due to their easy accessibility and cost effectiveness. Due to greater attentiveness concerning significance of conventional medicine in health care, research on medicinal plants would be valuable. The plants of genus Terminalia, comprising of 250 species, are widely distributed in tropical areas of the world. Fruits of Terminalia chebula (Family: Combretaceae) commonly known as black Myroblans in English and Harad in Hindi, are widely grown in Pakistan and India among many Asian and African countries and is a popular folk medicine. T. chebula has been studied for its homeostatic, antitussive, laxative, diuretic and cardiotonic activities. This article gives a vivid account of T. chebula as a natural product and aims to (i) to refresh the importance of T. chebula to the medicinal plant researchers and (ii) to presents new information such of T. chebula.

Antimicrobial activities of Conyzolide and Conyzoflavone from Conyza canadensis

Antibacterial and antifungal activities of the two isolated compounds from Conyza canadensis have been reported in the current study. The two isolated compounds i.e. Conyzolide (1) and Conyzoflavone (2) were tested against six bacterial and five fungal strains, employing hole diffusion and macrodilution methods. Both the compounds showed significant activities against the tested pathogens with special reference to E. coli, P. aeruginosa, S. aureus, Trichophytom longifusus, C. albicans, and C. glaberata. Conyzolide revealed comparatively better antibacterial activity against E. coli (minimum inhibitory concentration (MIC): 25 µg/mL) in comparison to Conyzoflavone. However, in case of antifungal activities, Conyzoflavone exhibited superior antifungal activity against C. albicans (MIC: 10 µg/mL) as compared to Conyzolide.

Effect of Bacopasides on acquisition and expression of morphine tolerance

Opioids are extensively used for the management of both chronic malignant and non malignant pains. One major serious limitation associated with chronic use of opioids is the development of tolerance to its analgesic effect. The effect of Bacopa monnieri, a renowned ayurvedic medicine for acquisition and expression of morphine tolerance in mice, was investigated. Bacopa monnieri, n-Butanol fraction was analyzed on High performance liquid chromatography (HPLC), for Bacopaside A major components i.e. Bacoside A(3), Bacopaside ll and Bacosaponin C. Antinociceptive effect of n-Butanol extract of Bacopa monnieri (n Bt-ext BM) (5, 10 and 15 mg/kg) was assessed on hot plate. Effect of different doses of n Bt-ext BM on morphine antinociception was also assessed. n Bt-ext BM was also screened for development of tolerance to antinociceptive effect of Bacopa monnieri by administering 15 mg/kg n Bt-ext BM for seven days. Tolerance to morphine analgesia was induced in mice by administering intraperitoneally (I.P.) 20 mg/kg morphine twice daily for five days. Acute and Chronic administration of 5, 10 and 15 mg/kg n Bt-ext BM significantly reduced both expression and development of tolerance to morphine analgesia in mice. Additionally, Bacopa monnieri was found to enhance antinociceptive effect of morphine in intolerant animals. However, no tolerance to Bacopa monnieri antinociceptive effect was observed in seven days treatment schedule. These findings indicate effectiveness of Bacopa monnieri for management of morphine tolerance.

Molecular interactions of 4-acetoxy-plakinamine B with peripheral anionic and other catalytic subsites of the aromatic gorge of acetylcholinesterase: Computational and structural insights

Abstract Context: A steroidal alkaloid, 4-acetoxy-plakinamine B (4APB), is a recently discovered marine natural product with inhibitory effect against acetylcholinesterase (AChE), but its mechanism of interaction with the enzyme remains to be elucidated. Objective: The main objective was to study molecular binding mode of the compound, its interactions with catalytic subsites and molecular mechanism behind its significant inhibitory effect. Materials and methods: All possible interactions of ligands in the binding sites were analyzed using FRED 2.1 and the OMEGA pre-generated multi-conformer library. Results: Dipole–dipole interactions were observed between the secondary amino group of 4APB and Ser200 at a distance of 3.91 Å and also with Gly117 and Gly118. A further dipole–dipole interaction was between Arg289 and the heterocyclic nitrogen. Hydrogen bonding interactions were observed between Tyr130 and secondary amino and C-4 acetyl groups as well as between heterocyclic nitrogen and Phe288 at a distance of 3.04 Å. Hydrophobic interactions were evident between rings C/D of 4APB and with Phe288, Phe330 and Phe331. The computational studies revealed 4APB’s critical molecular interaction with amino acids of peripheral active (PAS) and anionic (AS) subsites. Discussion: Our data provided molecular evidence for the mixed competitive inhibitory effect of 4APB. For lead optimization, structural insights revealed the N-methyl group of 4APB could be replaced by NH2 moiety to generate a more favorable hydrogen bonding with Glu199. A polar group insertion such as NH2 or OH at certain sites of the 4APB skeleton is also recommended. Conclusion: These computational insights explained the mixed-competitive enzyme kinetic behavior of 4APB. This study outlines a strategy for designing novel derivatives of 4APB with potentially better AChE inhibitory activities through interaction at the PAS and AS sites.

Amberlite IR-120H as a recyclable catalyst for the synthesis of 1,8-dioxo-octahydroxanthene analogs and their evaluation as potential leishmanicidal agents

Bioactive 1,8-dioxo-octahydroxanthene analogs were synthesized by employing Amberlite IR-120H as a recyclable heterogeneous catalyst in acetonitrile. Their in vitro cytotoxicities and leishmanicidal activities were evaluated. The synthetic protocol involves a Knoevenagel condensation followed by a Michael addition and finally a cyclodehydration of dimedone with an aldehyde. Among the solvents used for this protocol, acetonitrile gave the best results in terms of isolated yield. Being a one-pot reaction, this protocol presents several advantages over the previously reported methods in terms of its low cost, catalyst recyclability, atom economy, and convenient work-up in addition to the respectable resulting isolated yield. The non-cytotoxic nature of these 1,8-dioxo-octahydroxanthene analogs provides a safer route for related biological studies. Some of the prepared materials (3b, 3c, 3d, 3e and 3g) showed significant leishmanicidal activity against Leishmania major (DESTO) promastigotes in comparison to the standard compound, pentamidine.

Nigella sativa provides protection against metabolic syndrome

The seeds of Nigella sativa have been used in folk medicine all over the world. The plant has been of interest due to its low degree of toxicity and beneficial pharmacological properties like antihypertensive, hypoglycemic, antifungal, anti-inflammatory, antihistaminic, antioxidant, along with significant anti-neuplastic activities. The present clinical study was undertaken to ascertain the adjuvant effect of Nigella seeds on various clinical and biochemical parameters of metabolic syndrome. After final diagnosis and considering inclusion and exclusion criteria, one hundred and fifty nine patients were enrolled in this study. Patients were divided into two groups. In Group I (standard group), patients were advised to take simvastatin 10 mg once a day, metformin 500 mg twice a day, Enalapril 10 mg once a day, Atenolol 50 mg once a day and clopidagrel 75 mg once a day for a period of six weeks. In Group II ( Nigella seeds group), patients were advised the above standard medication plus Nigella seeds 250 mg twice daily for a period of six weeks. Blood sugar both fasting and postprandial, fasting lipid profile and different parameters of obesity were recorded before therapy and after completion of therapy. It was found that the addition of Nigella seeds provide beneficial effects in all the clinical and biochemical parameters for the adult’s treatment panel-III of metabolic disorders especially in fasting blood sugar, low density lipoproteins and high density lipoproteins. No sign of toxicity of the plant appeared in the Group II. Improvement in all other parameters like blood pressure, circumference of waist and serum triglyceride was also observed. Thus, Nigella seeds were found to be effective as an adjuvant therapy in patients of dyslipidemia and hyperglycemia. Keywords: Nigella sativa , toxicity, hyperglycemia, adjuvant, antihistaminic, antioxidant, patients

Once daily controlled release matrix tablet of Prochlorperazine maleate: Influence of Ethocel® and/or Methocel® on in vitro drug release and bioavailability

Context: Controlled release (CR) matrix tablet of Prochlorperazine maleate was developed to improve its patient compliance. Methods: Tablet formulations F1, F2 and F3 based on different concentrations of Methocel® K100 LV-CR Premium, were compacted by direct compression method while tablet formulations F4, F5 and F6, based on distinct blends of Methocel® K100 LV-CR Premium and Ethocel® Standard 7FP Premium, were compressed by flow-bound dry granulation-slugging method. The prepared powder mixtures, granules and tablets were evaluated for their physicochemical performance. Bioequivalence study of the optimized test tablet versus reference-conventional Stemitil® tablet was conducted on rabbits, using HPLC-UV system at λmax 254 nm. Results: The test tablet, containing 28% Methocel® and 58% Ethocel® (F6) exhibited desired zero order kinetics for 24 h and was found stable at accelerated storage conditions for 6 months. In vitro drug release rate decreased as the Ethocel® content in the blend was increased, perhaps due to slower penetrability of water. Hydrodynamic conditions and hardness of tablets could not affect drug release kinetics. The tablet displayed significantly (p < 0.05) optimized peak drug concentration-Cmax (45 ± 3.42 vs. 64.5 ± 4.03), extended half life-t1/2 (16.071 ± 3.97 vs. 5.257 ± 1.314 h) and bioequivalence to the reference tablet taken three times a day (1409 ± 15 ng·h/mL vs. 1346 ± 23 ng h/mL). The tablet showed strong Level A correlation (R2 = 0.8458) between drug absorbed in vivo and drug released in vitro. Conclusions: The developed tablet may be adopted by pharmaceutical industry to improve patient compliance of the Prochlorperazine maleate.

Release pattern of three new polymers in Ketoprofen controlled-release tablets

The objective of the study was to formulate and evaluate sustained release polymeric tablets of ketoprofen for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with three different types of newly synthesized polymers and one grade of ethyl cellulose ether derivatives (FP100 premium) in several drug-to-polymer ratios (D:P ratio 10:1, 10:2 and 10:3) were compressed into tablets using the direct compression method. They were examined for their physical properties and appearance. Tablets dimensional tests (thickness, diameter) and Q.C tests (hardness, friability, disintegration) were performed according to the USP methods. For in vitro drug release studies of Ketoprofen controlled release (CR) tablets, the USP Method-1 (Rotating Basket Method) was used with Pharma test dissolution apparatus (D-63512 Hainburg, Germany). The medium used for dissolution was phosphate buffer having a pH of 7.4 kept at constant temperature of 37±1°C. In order to analyze the drug release kinetics from each of the prepared matrices, five different mathematical models were applied to the release data including zero order kinetics, first order kinetics, Higuchi kinetics, Hixson Crowell kinetics and Korsmeyer Peppas equations were applied to the release data. The results obtained from different parameters showed that polymers: Polyglycolide, PGA-cocaprolactone, PGA-co-pentadecalactone and Ethocel FP100 premium can be used successfully in order to develop directly compressed prolonged release tablets of slightly soluble drugs such as ketoprofen. Particle size of polymer is a determining factor in controlling the release of ketoprofen from tablets. Ethocel standard FP100 polymers extend the release rates of drug more efficiently than the conventional granular form of the other three polymers. Further, the three new polymers and Ethocel FP100 could efficiently extend the release of the drugs as compared to the reference conventional formulation.

Effect of cisplatin on glutathione redox status in isolated plasma and cytosolic fraction

Cisplatin has been used therapeutically in the treatment of malignant tumors. Meanwhile, the major limitations associated with cisplatin are its side effects in the form of nephrotoxicity, neurotoxicity, emetogensis and emerging resistance. Most of these problems are due to its adverse effects on the body’s endogenous cytoprotective molecules like glutathione (GSH). In current study, the effect of glutathione on the improvement of cisplatin therapy along with control on its growing problem of resistance was emphasized. The effect of cisplatin on the chemical and metabolic status of glutathione was evaluated in human venous blood after its separation in to plasma and cellular fraction using ultra violet (UV)-visible spectrophotometer. The glutathione in isolated plasma and cellular fractions of the blood was exposed to different concentrations of cisplatin. It was found that there was a gradual depletion in the concentration of reduced glutathione. Similarly, time-dependent effect of cisplatin was also evaluated on the status of glutathione, in which positive correlation was found between exposure of glutathione to the given concentrations of cisplatin and the depletion of reduced glutathione as the time passed from 0 to 5 h. This depletion in the concentration of reduced GSH is either due to formation of Pt-SG complex or due to the conversion of this multifunctional molecule (glutathione) to its physiologically inactive disulfide form (GSSG). This study was carried out in vitro, which in principle depicts a model of in vivo reaction. This decrease in blood GSH levels after cisplatin treatment will result in decreased antioxidant capacity of the blood, which in turn will result in numerous pathological conditions.

Role of gastrointestinal motility/gastric emptying in cisplatin-induced vomiting in pigeon

hexane (CS-HexFr 5, 10 and 15 mg/kg), n-butanol (CS-ButFr 5 and 10 mg/kg) and methanol fractions (CS-MetFr 10 and 15 mg/kg) were examined against cisplatin-induced vomiting and their possible effects on GIT motility/gastric emptying in pigeon by charcoal propulsion method. Standard prokinetic drugs metoclopramide (MCP, 30 mg/kg) and carbachol (0.1 mg/kg) were screened in combination with CS-HexFr to estimate the involvement of gastric emptying and GIT motility in cisplatin-induced vomiting. CS-HexFr at the dose of 10 mg/kg once and twice daily attenuated cisplatin-induced vomiting up to 55.45 and 68.86% (P 0.05). CS-HexFr 10 mg/kg caused up to 26.62% suppression in GIT motility as compared to vehicle treatment group. MCP (30 mg/kg) and carbachol (0.1 mg/kg) completely antagonized the suppression caused by CS-HexFr 10 mg and in combination enhanced the antiemetic profile at 12 to 24 h, while no enhanced activity was observed at 0 to 12 h. The findings suggest that the decrease in GIT motility/gastric emptying is playing a role at least in part in the vomiting induced by cisplatin commencing just after the peak vomiting response of acute phase in pigeon. Key words: