Development of Vanadometric System for Spectrophotometric Determination of Timolol in Pure and Dosage Forms

Purpose: To develop a simple vanadometric spectrophotometric method for the assay of timolol.Methods: The oxidation reactions were performed at optimum conditions of 3 mL 20 % v/v H2SO4, 6.5 % w/v ammonium metavanadate, 40 - 60 ºC and 5 min for full colour (blue) development. The proposed method was validated in accordance with International Council on Harmonization (ICH) guidelines Q2 (R1) and applied to assay commercial timolol.Results: Oxidation of timolol occurred at 504 nm wavelength. The developed method recovered 99.25 - 102.00 % of timolol in pre analyzed formulations and 99.85 - 102.00 % of the manufacturers’ claim in commercial samples with RSD < 2 %. Linearity of 2 - 20 ppm (R2 = 0.9995),as well as accuracy, 98 - 101 %; precision, 0.98 % (intraday) and 1.25 % (interday); robustness, 0.95 %; LOD, 0.256 ppm; LOQ, 0.425 ppm; and robustness, 0.95 - 1.10 %, were obtained.Conclusion: The developed method is simple, sensitive, low-cost, accurate, reproducible, robust and rugged, and compares well with some complex methods for assay of timolol maleate in pure and dosage forms.Keywords: Ammonium metavanadate, Spectrophotometry, Vanadometric, Timolo

Potential antidiabetic and antioxidant activities of a heliangolide sesquiterpene lactone isolated from Helianthus annuus L. Leaves

Heliangolide is a naturally occurring sesquiterpene lactone and its derivatives are biologically active compounds present in most medicinal plants. This study evaluated the antioxidant and antidiabetic properties of a heliangolide sesquiterpene lactone isolated from Helianthus annuus L. leaves. The heliangolide sesquiterpene lactone was isolated through combination of solvent-solvent partitioning, column chromatography, thin layer chromatography and high performance-liquid chromatography techniques. The antioxidant activity of the compound was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide radical scavenging assays while the antidiabetic effects were investigated in alloxan-induced diabetic rats. The heliangolide derivative at 954.2 µmol L–1 showed 23.7 % DPPH and 26 % nitric oxide radical inhibitions compared with 96.6 and 50.9 %, resp., displayed by the controls (2,271.2 µmol L–1). It also reduced the fasting blood glucose (FBG) levels in a time-dependent manner. The highest activity was recorded within 6 h post-treatment at 0.2 mmol kg–1 bm. The heliangolide derivative exhibited significant (p < 0.05) antioxidant and antidiabetic properties and provides basis for further development of constituents of Helianthus annuus leaves for the management of such diseases

Anti-inflammatory activity and accelerated stability studies of crude extract syrup of Cannabis sativa

Purpose: To formulate Cannabis sativa-based syrup and investigate its anti-inflammatory potential and the stability of the formulation under stress conditions.Methods: The syrup was prepared using different combinations of crude C. sativa resin, propylene glycol, aspartame, sucrose, sodium metabisulphite (SMBs) and ethylenediaminetetraacetic acid (EDTA). The stability of the formulations was determined under accelerated temperature conditions. The anti-inflammatory activity of the resin and different formulations were evaluated by the egg albumin induced paw edema model in rats. Biochemical assay was determined by Reitman and Frankel colorimetric assay method while hematological assay was evaluated by standard protocols.Results: EDTA-containing syrup (CE) was the most stable with estimated shelf-life of 2204 days (K25ºC, 4.78 x 10-5/day). Higher propylene glycol levels significantly improved anti-inflammatory activity compared to those containing a lower amount. All the formulations showed anti-inflammatory activity higher than the crude resin with a dose-dependent inhibition of paw edema compared with the control. There was no significant difference (p &lt; 0.05) between the serum glutamate-oxaloacetate transaminase (SGOT, 13.821 ± 0.190 - 16.008 ± 1.012), serum glutamate-pyruvate transaminase (SGPT, 19.241 ± 1.027 - 22.901 ± 1.093) and urea (9.812 ± 0.252 - 10.054 ± 0.252) levels of the treated and 16.856 ± 1.053, 24.960 ± 0.101 and 10.654 ± 0.925 units/L of the control animals respectively. With the exception of eosinophil that disappeared from the blood in the third week, all the hematological parameters showed a gradual increase in lymphocytes, neutrophils, monocytes, packed cell volume (PCV), white and red blood cell counts in the third week compared to control.Conclusion: Formulation of C. sativa as syrup using efficient carriers improves the pharmacological activity of the crude extract. SMBs and EDTA significantly enhance the stability of the syrup with no observable biochemical and hematological changes in treated animalsKeywords: Cannabis sativa, Syrup, Anti-inflammatory, Stability, Hematologica

Chemical constituents of Combretum dolichopetalum: Characterization, antitrypanosomal activities and molecular docking studies

Purpose: To evaluate the in vitro activities of a gallic acid ester and two apigenin flavone glucoside constituents of Combretum dolichopetalum against Trypanosoma brucei brucei s427 (Tbs427) and Trypanosoma congolense IL3000 (Tc-IL3000), and their interactions with a lysosomal papain-like cysteine protease (CP) enzyme in silico.Methods: Anti-trypanosomal activity-guided separation of ethyl acetate fraction using column chromatographic (CC) technique and purification of the CC sub-fractions with semi-preparative HPLC yielded three (1-3) compounds. The structures were characterized based on nuclear magnetic resonance (NMR) spectroscopic analyses and tested for activities against Tbs427 and Tc-IL3000. All the compounds were subjected to molecular docking studies for the inhibition of trypanosomal cathepsin B (TbCatB) CP.Results: An ester (1), a butyl gallate, and two positional isomeric apigenin flavone glucosides (2, 3) were identified. The compounds 2 (vitexin) and 3 (isovitexin) showed low in vitro IC50 against the tested parasites. However, 2 (IC50, 25 μM) was more potent than 3 (IC50, 68 μM) against Tbs427 while both were equipotent (IC50 = 2, 11.5 μM and 3, 10.8 μM) against Tc-IL3000. Compound 1 (butyl gallate) showed higher activity against Tc-IL3000 (IC50 = 0.80 μM) than to Tbs427 (IC50, 2.72 μM). The molecular docking study showed that all the compounds had minimum binding energies with a higher affinity towards the active pocket of TbCatB compared to the controls and native inhibitor (CA074).Conclusion: The relatively high in vitro activities and their strong affinity for TbCatB support the need for further optimization of the compounds towards lead identification against animal trypanosomiasis

In-vivo antitrypanosomal effect and in-silico prediction of chronic toxicity of N-methylholaphyllamine in rats

Purpose: To determine the in-vivo anti-trypanosomal effect and sub-chronic toxicity of Nmethylholaphyllamine (MHA) isolated from H. africana against Trypanosoma brucei in rats and also to predict its toxicity by an in-silico method. Methods: Parasitemia was induced in rats with 1.5 x 105/mL trypanosomes and treatment commenced 5 days post-infection for 12 days. The rats were treated with MHA (3.5 μM/rat) for 5 days and with diminazene (3.5 mg/kg) for 2 days and were monitored every other day during and after treatment for the level of parasitemia and PCV. The chronic toxicity study was carried out with a 28-day sub-chronic toxicity cycle protocol while the toxicity was predicted in-silico with ProTox-II which is freely available on a web server. Results: MHA exhibited anti-trypanosomal effect in infected rats leading to the restoration of PCV to baseline values (≥ 40 %) on the 14th day and consequent disappearance of parasitemia on day 17 post-infection with no relapse. The slight changes in clinical observation, weight, feed consumption, clinical and histopathology of high-dose MHA rats were not significant (p &lt; 0.05) and were not attributed to the treatment. Apart from MHA-induced immunotoxicity observed in in-silico prediction, no other predicted toxicities were significant; however, few undetected toxicities were found to be mediated by amine oxidase A, androgen and/or histamine, H1 receptors toxicophore fit. Conclusion: The high in-vivo antitrypanosomal effect and non-toxicity of MHA in this study further provide useful empirical data for lead optimization of MHA to combat sleeping sickness

Potent antitrypanosomal activities of 3-aminosteroids against African trypanosomes: investigation of cellular effects and of cross-resistance with existing drugs. Molecules

Treatment of animal African trypanosomiasis (AAT) requires urgent need for safe, potent and affordable drugs and this has necessitated this study. We investigated the trypanocidal activities and mode of action of selected 3-aminosteroids against Trypanosoma brucei brucei. The in vitro activity of selected compounds of this series against T. congolense (Savannah-type, IL3000), T. b. brucei (bloodstream trypomastigote, Lister strain 427 wild-type (427WT)) and various multi-drug resistant cell lines was assessed using a resazurin-based cell viability assay. Studies on mode of antitrypanosomal activity of some selected 3-aminosteroids against Tbb 427WT were also carried out. The tested compounds mostly showed moderate-to-low in vitro activities and low selectivity to mammalian cells. Interestingly, a certain aminosteroid, holarrhetine (10, IC50 = 0.045 ± 0.03 µM), was 2 times more potent against T. congolense than the standard veterinary drug, diminazene aceturate, and 10 times more potent than the control trypanocide, pentamidine, and displayed an excellent in vitro selectivity index of 2130 over L6 myoblasts. All multi-drug resistant strains of T. b. brucei tested were not significantly cross-resistant with the purified compounds. The growth pattern of Tbb 427WT on long and limited exposure time revealed gradual but irrecoverable growth arrest at ≥ IC50 concentrations of 3-aminosteroids. Trypanocidal action was not associated with membrane permeabilization of trypanosome cells but instead with mitochondrial membrane depolarization, reduced adenosine triphosphate (ATP) levels and G2/M cell cycle arrest which appear to be the result of mitochondrial accumulation of the aminosteroids. These findings provided insights for further development of this new and promising class of trypanocide against African trypanosomes

Personalized medicine in psychiatry: problems and promises

The central theme of personalized medicine is the premise that an individual’s unique physiologic characteristics play a significant role in both disease vulnerability and in response to specific therapies. The major goals of personalized medicine are therefore to predict an individual’s susceptibility to developing an illness, achieve accurate diagnosis, and optimize the most efficient and favorable response to treatment. The goal of achieving personalized medicine in psychiatry is a laudable one, because its attainment should be associated with a marked reduction in morbidity and mortality. In this review, we summarize an illustrative selection of studies that are laying the foundation towards personalizing medicine in major depressive disorder, bipolar disorder, and schizophrenia. In addition, we present emerging applications that are likely to advance personalized medicine in psychiatry, with an emphasis on novel biomarkers and neuroimaging