Herbal Formulation Comprised of Methanol Extracts of Tribulus terristris L. and Zingiber officinale Roscoe Has Antihypertensive Effects.

People prefer to use medicinal plants rather than chemical compounds because they are low cost and have fewer adverse events. Zingiber officinale Roscoe is a natural dietary rhizome with anti-oxidative, anti-inflammatory and anti-carcinogenic properties. Tribulus terrestris L. has been used for the treatment of impotence, to enhance sexual drive and performance and for its diuretic and uricosuric effects. The aim of this study was to evaluate the combined effect of 2 extracts, Tribulus terristris and Zingiber officinale (TZ) for antioxidant, enzyme modulation, liver function, kidney function, blood profile and anti-hypertensive effects, which may pave the way for possible therapeutic applications. Antioxidant potential was measured with the 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical method antioxidant assay (DPPH) and kojic acid was used as the standard drug for tyrosine inhibition assay. The effect of TZ on biochemical parameters of the liver (alanine transferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], total serum protein, total serum albumin, serum bilirubin), kidney (blood urea and creatinine) and hematology (hemoglobin, red blood cells [RBC], platelets, thin-layer chromatography, neutrophils, eosinophils, lymphocytes, monocytes, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) of Wister rats were studied by administering 100, 250 and 500 mg/kg-1 body weight TZ dose orally for 28 days. Antihypertensive effects were measured by the invasive method. The results showed that the scavenging percentage of TZ was 78.5 to 80.4, with an IC50 value of 1166.7 µg/ ml and tyrosinase inhibition was 72% compared with 93% for kojic acid. Different doses (100, 250 and 500 mg/kg) did not show an increase in serum biomarkers of liver and renal parameters. A significant increase in hemoglobin, erythrocytes, hematocrit, white blood cells (WBC) and lymphocytes with no significant increase/decrease in platelet count was observed but blood pressure was significantly decreased. Therefore, we concluded that TZ is safe and can be used in the treatment of hypertension.

Co-Combination of Pregabalin and Withaniacoagulans-Extract-Loaded Topical Gel Alleviates Allodynia and Hyperalgesia in the Chronic Sciatic Nerve Constriction Injury for Neuropathic Pain in Animal Model.

The current study reports the fabrication of co-combination gel using Pregabalin and Withania coagulans fruit extract to validate its effectiveness for neuropathic pain in chronic constriction injury (CCI) rat models. Three topical gels were prepared using Carbopol 934 through a pseudo-ternary phase diagram incorporating the Pregabalin (2.5%), Withania coagulans extract (2%), and co-combination of both Pregabalin (2.5%) and Withania coagulans extract (2%). Gels were characterized. FTIR showed a successful polymeric network of the gel without any interaction. The drug distribution at the molecular level was confirmed by XRD. The AFM images topographically indicated the rough surface of gels with a size range from 0.25 to 330 nm. DSC showed the disappearance of sharp peaks of the drug and extract, showing successful incorporation into the polymeric network of gels. The in vitro drug release of co-combination gel was 73% over 48 h. The mechanism of drug release by combination gel was Higuchi+ fickian with values of n (0.282) and R2 (0.947). An in vivo study for pain assessment via four methods: (i) heat hyperalgesia, (ii) cold allodynia, (iii) mechano-hyperalgesia, and (iv) dynamic mechano-allodynia, confirmed that topical treatment with co-combination gel reduced the pain significantly as indicated by the p value: R1 (p < 0.001), R2 (p < 0.001), R3 (p < 0.015), and R4 (p < 0.0344). The significance order was R2 (****) > R1 (***) > R3 (**) > R4 (*) > R5 (ns).

Preparation, Characterization of Pregabalin and Withania coagulans Extract-Loaded Topical Gel and Their Comparative Effect on Burn Injury.

The current study depicts the comparative effects of nanogel using Withania coagulans extract, pregabalin alone, and a co-combination gel. The gels prepared were then analyzed for conductivity, viscosity, spread ability, globule size, zeta potential, polydispersity index, and TEM. The globule size of the co-combination gel, determined by zeta sizer, was found to be (329 ± 0.573 nm). FTIR analysis confirms the successful development of gel, without any interaction. Drug distribution at the molecular level was confirmed by XRD. DSC revealed no bigger thermal changes. TEM images revealed spherical molecules with sizes of 200 nm for the co-combination gel. In vivo studies were carried out by infliction of third degree burn wounds on rat skin, and they confirmed that pregabalin and Withania coagulans heals the wound more effectively, with a wound contraction rate of 89.95%, compared to remaining groups. Anti-inflammatory activity (IL-6 and TNF-α), determined by the ELISA technique, shows that the co-combination gel group reduces the maximum inflammation with TNF-α value (132.2 pg/mL), compared to the control (140.22 pg/mL). Similarly, the IL-6 value was found to be (78 pg/mL) for the co-combination gel and (81 pg/mL) in the case of the control. Histopathologically, the co-combination gel heals wounds more quickly, compared to individual gel. These outcomes depict that a co-combination gel using plant extracts and drugs can be successfully used to treat burn injury.

Development, characterization and evaluation of in vitro anti-inflammatory activity of Withania coagulans extract and extract loaded microemulsion.

Herbal medicines are gaining importance due to more advantages and less toxic effects. Withania coagulans is natural plant that possesses multiple activities. Its main constituents are withaferin and withanolide. The purpose of present study is to identify main constituent of Withania coagulans and preparation of extract loaded micro emulsions. Withania coagulans fruit extract in methanol/chloroform (1:1) was collected in semisolid form and LCMS was done to identify active compound, and then micro emulsions were prepared using Tween 80: Transcutol (1:1) Frankincense oil, and water to enhance its stability for topical application. Five formulations were prepared by Pseudo ternary phase diagram and evaluated for pH, conductivity, viscosity, drug contents, particle size analysis, and polydispersity. Withania coagulans extract was evaluated for anti-bacterial activity against (Staphylococcus aureus, E. coli, and S. typhi) and anti-fungal activity against (Candida albicans and Aspergillus niger). Anti-inflammatory activity was checked for both extract and Extract based micro emulsion. Among all five formulations F5 shows best physiochemical properties with small globule size, good stability and high anti-inflammatory activity. Based on these results it was concluded that Withania coagulans extract loaded micro emulsions can be used for topical application with promising anti-inflammatory activities. Data for in-vivo studies for checking the topical effect of Withania coagulans is provided elsewhere.

Cross-linked pH-sensitive pectin and acrylic acid based hydrogels for controlled delivery of metformin.

The purpose of present study is to load Metformin HCl into pH-sensitive hydrogels to have sustained release over a period of time. The hydrogel was synthesized from naturally occurring polysaccharide pectin and monomer acrylic acid (AA) using ethylene glycol dimethacrylate (EGDMA) as cross-linker under controlled conditions for polymerization at 45°C for one hr, 50°C for two hrs, 55°C for three hrs, 60°C for four hrs and finally 65˚C for 12 hrs. Hydrogels were characterized for dynamic/equilibrium swelling, sol-gel fraction analysis, diffusion coefficient and percentage porosity. Hydrogels were tested by FTIR, XRD and SEM for structure and surface morphology respectively. Experimental in-vitro drug release data was applied to kinetic models. Formation of strong bonding between pectin and AA was supported by FTIR. The intensity of XRD peaks was reduced in non-loaded and loaded hydrogels compared to active drug substance. The non-loaded hydrogel showed discrete porous structure whereas loaded hydrogels were fibrous and smooth. Hydrogels showed higher swelling in the solutions of pH 6.5 and 7.5 as compared to in the solutions of pH 1.2 and 5.5. The diffusion coefficient decreases with the increase of AA and pectin concentrations. It was observed upon increasing the EGDMA concentration porosity decreases. The release of drug from all compositions of hydrogels took place through non-Fickian diffusion mechanism.

Development, characterization and evaluation of in-vitro anti-inflammatory activity of ginger extract based micro emulsion.

Zingeber officinale is a commonly used plant which has been shown to possess anti-inflammatory activity. The active compounds present in ginger are gingerols, shagaols and paradol. The aim of this study was formulation of topical microemulsion system to enhance the solubility and stability of ginger extract, as it is unstable in the presence of light, air, heat and long term storage, and to evaluate its anti-inflammatory activity. The solubility of ginger extract in different oils, surfactants, and co-surfactants was determined in order to find the optimal components for microemulsion. IPM was selected as oil phase, tween 80 and PEG 400 were selected as surfactant and co-surfactant respectively based on highest solubility values. Pseudo-ternary phase diagram was constructed in order to find out the microemulsion region. The prepared microemulsions were evaluated for pH, viscosity, conductivity, refractive index, globular size, zeta potential, polydispersity index, ginger extract content. The formulation F1 showed best physicochemical properties with smallest globular size. It also showed significant (p<0.05) anti-inflammatory effect as compared to reference piroxicam drug solution. Based on the results, it is concluded that ginger extract can be used to develop stable microemulsion system and promising anti-inflammatory activity.