OPTIMIZATION OF BACOSIDE A LOADED SNEDDS USING D-OPTIMAL MIXTURE DESIGN FOR ENHANCEMENT INSOLUBILITY AND BIOAVAILABILITY

Objective: The objective of present study is to enhance solubility and bioavailability of poorly soluble bacoside A present in Bacopa monnieri extract using self nano emulsifying drug delivery system (SNEDDS) for the treatment of Alzheimer's disease.Methods: Solubility of the drug was assessed in various oils (edible as well as synthetic oil), surfactant and co-surfactant by saturation solubility study. Pseudo-ternary phase diagram was used to obtain appropriate concentration ranges of components include oil, surfactant and co-surfactant.Results: From the result of saturated solubility study and phase diagram, oleic acid, tween 20 and ethanol was selected as oil, surfactant and co-surfactant. The D-Optimal mixture design was used to optimize the formulation on the basis of solubility of drug and dilution potential. In vitro dissolution, study showed 89% of drug release from optimized SNEDDS formulation compared to untreated drug extract with 24% of drug release in 60 min. Ex vivo diffusion study showed more than 90% of drug diffused from optimized SNEDDS formulation compared to pure extract.Conclusion: In a nutshell, the developed SNEDDS formulation using the design of experimentation approach held great potential as a possible alternative to traditional oral formulations of poorly soluble Bacoside A to improve solubility and bioavailability

Effect of herbal combination of triphala and Garcinia cambogia extracts on liver function test and kidney function test in high fat diet induced obesity in rats

Background: Obesity, a global epidemic, is a major risk factor for diabetes mellitus and cardio vascular diseases. Despite advances, the pharmacotherapy for obesity remains limited. Almost all medications for long term management of obesity have health issues. Due to the adverse drug reactions (ADRs) associated with many antiobesity medicines, the clinical trials are focussing on screening herbal medicines for use in the treatment of obesity, which have minimal ADRs.Methods: Rats were divided into eight groups of six each. The rats were first made obese by feeding high fat diet (HFD) for three weeks. Then treatment with the herbal extracts was given simultaneously with the HFD to the experimental groups. Rats were fed HFD for six weeks along with herbal extracts and the effect on their liver function test and kidney function test were evaluated.Results: The rats fed HFD and supplemented with herbal preparations of Triphala and G. cambogia for six weeks, showed significant improvement in liver function test and kidney function test related parameters as compared to the control group rats fed with HFD alone.Conclusions: Triphala and G. cambogia can counter the effects of HFD intake and have the potential for use as anti-obesity agents with desirable liver function test and kidney function test related parameters modulating properties

Novel poly herbal muco-adhesive formulation for treatment of oral aphthous ulcer

Background: Oral ulcers are the most frequent lesions that cause discomfort for which the patients seek treatment for alleviating pain and facilitate early healing. Various treatment modalities from modern medicine and Ayurveda are used in the form of ointments and mouthwashes with varying efficacy. Anti-inflammatory medicines, enzymatic preparations, gamma globulins and immune suppressants have been used.Methods: Extracts of five chosen herbs, Glycyrrhiza glabra, Acacia catechu, Punica Granatum, Curcuma longa and Mentha piperita were used for preparing mucoadhesive gel for the treatment of oral aphthous ulcers of any etiology. Gel was prepared by cold method of Schmolka at M/s Pharmanza Herbals Pvt. Ltd., India. Five formulations were prepared with using different concentration of active pharmaceutical ingredient (API) extracts.Results: Formulations were analyzed for different physical and chemical properties. Preliminary trial was done with five formulations. The F5 formulation has the premier viscosity because of its higher polymer content; it is able to remain on mucous surface long enough to release its API effect. Since the uniformity, proper appearance, stability and acceptable viscosity and gel strength the F1 formulation was selected as the superior formulation which could prove ideal for treatment of oral aphthous ulcers.Conclusions: The results provide strong evidence that polyherbal gel containing extracts of Glycyrrhiza glabra, Acacia catechu, Punica granatum, Curcuma longa and Mentha piperita on the basis of their analgesic, anti-inflammatory, antioxidant, wound healing, antimicrobial and local anesthetic properties can be used as an effective and safe alternative for the management of aphthous ulcers

EVALUATION OF IN VITRO ANTICANCER ACTIVITY OF SYMPLOCOS RACEMOSA BARK AGAINST HEPATOCELLULAR CARCINOMA

Objective: To investigate in vitro anticancer activity of different extracts of bark of Symplocos racemosa against hepatocellular carcinoma.Methods: Different successive extracts of Symplocos racemosa bark were prepared using hexane, chloroform, ethyl acetate, n-butanol and water and were tested in vitro for cytotoxicity using (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay in rat normal liver cells (BRL-3A) and human hepatocellular carcinoma (Hep3B) cells.Results: Ethyl acetate and chloroform extract of Symplocos racemosa exhibited cytotoxicity against human hepatocellular carcinoma (Hep3B) cells in vitro with IC50 value (µg/ml) of 63.45 and 75.55 respectively and not affected the normal liver (BRL-3A) cells.Conclusion: Symplocos racemosa bark extracts showed potential cytotoxic effects on human hepatocellular carcinoma cells. The anticancer activity exhibited by ethyl acetate and chloroform extract might be due to presence of phenolics and flavonoid constituents present in the bark. Ethyl acetate extract can further be explored for possible cytotoxic activity using in vivo models of liver cancer.Â

Rapid and sensitive High-Performance Thin-Layer Chromatographic (HPTLC) method for identification and quantification of luteolin by densitometry in Kasamarda (Cassia occidentalis L.)

Kasamarda (C. occidentalis L.) is a traditional herb recently recognized as a potential nutraceutical in bone health. The current botanical nutraceutical regulations require consistent standardization for biological applications. The present study reported the standardization of bioactive flavonoid luteolin from Cassia occidentalis L. using validated high-performance thin-layer chromatographic (HPTLC) densitometric (DS) method. The mobile phase composition of toluene, ethyl acetate, and formic acid was optimized to separate and identify luteolin using silica gel 60F254 aluminum plates. The densitometric (DS) scanning was performed at 353 nm. This HPTLC-DS method was further validated as per ICH guidelines. The linearity was 200–700 ng/band with a correlation coefficient value of 0.994. The LOD and LOQ were found to be 54.06 ng/band and 163.84 ng/band, respectively. The recovery (88.38% and 100.72%) and precision (RSD,<5%) indicated method performance is robust and accurate for the routine analysis. Further, this bioactive flavonoid presence was confirmed and quantified by UV-spectrumin the sample matrix using this validated HPTLC-DS method. This HPTLC-DS method was robust, precise and accurate for quality control of active constituents present in C. occidentalis L

Rapid and sensitive High-Performance Thin-Layer Chromatographic (HPTLC) method for identification and quantification of luteolin by densitometry in Kasamarda (Cassia occidentalis L.)

700-706Kasamarda (C. occidentalis L.) is a traditional herb recently recognized as a potential nutraceutical in bone health. The current botanical nutraceutical regulations require consistent standardization for biological applications. The present study reported the standardization of bioactive flavonoid luteolin from Cassia occidentalis L. using validated high-performance thin-layer chromatographic (HPTLC) densitometric (DS) method. The mobile phase composition of toluene, ethyl acetate, and formic acid was optimized to separate and identify luteolin using silica gel 60F254 aluminum plates. The densitometric (DS) scanning was performed at 353 nm. This HPTLC-DS method was further validated as per ICH guidelines. The linearity was 200–700 ng/band with a correlation coefficient value of 0.994. The LOD and LOQ were found to be 54.06 ng/band and 163.84 ng/band, respectively. The recovery (88.38% and 100.72%) and precision (RSD,<5%) indicated method performance is robust and accurate for the routine analysis. Further, this bioactive flavonoid presence was confirmed and quantified by UV-spectrumin the sample matrix using this validated HPTLC-DS method. This HPTLC-DS method was robust, precise and accurate for quality control of active constituents present in C. occidentalis L

Safety assessment of Withania somnifera extract standardized for Withaferin A: Acute and sub-acute toxicity study

Background: The use of Withania somnifera is increasing due to a number of its chemical constituents found useful for health. Objective: The present study was carried out to investigate the potential adverse effects (if any) of a standardized Withania somnifera extract (WSE) in rats following acute and sub chronic administration. Materials and methods: The toxicity study was performed in Wistar rats by oral administration. An acute toxicity study was done at the dose of 2000 mg/kg. In the sub-acute study, Wistar rats (10/sex/group) were administered via gavage 0 (control), 500, 1000, 2000 mg/kg body weight/day of WSE for 28 days. Among two additional satellite groups, one group did not receive any drug while the second group received 2000 mg/kg/day for 28 days. At the end of study, the animals sacrificed and their body weight, hematology, serum chemistry, and histopathology evaluation was done. Results: In acute toxicity studies, oral LD50 of WSE in Wistar rats was greater than 2000 mg/kg body weight. Compared to the control group in sub-acute toxicity study, administration of extract did not show any toxicologically significant treatment related changes in clinical observations, ophthalmic examination, body weight gain, feed consumption, clinical pathology evaluation, and organ weight. Hematological and serum chemistry parameters were within the normal limits. Terminal necropsy did not reveal any treatment related gross or histopathological findings. Conclusion: Based on this study, the no-observed-adverse-effect-level of WSE is 2000 mg/kg body weight, the highest level tested

Evaluation of the wound healing effect of Nishamalaki, an Ayurvedic formulation comprising Curcuma longa and Phyllanthus emblica in aging rats

Abstract Background There are very few drugs available for healing wounds in the aged population, which is more prone to chronic cutaneous wounds that are particularly hard to heal and require a long healing process. This study which deals with age-related wound healing, investigates the healing effect of Nishamalaki, a classic antidiabetic Ayurvedic formulation comprising turmeric (Curcuma longa) and Indian gooseberry (Phyllanthus emblica), on cutaneous wounds in aging rats. Methods Rats with excision wounds of 7 mm created on their dorsal side received Nishamalaki (500 mg/kg p.o) daily, or a combination of Nishamalaki (500 mg/kg p.o) with 1% Nishamalaki gel applied on the wound or the reference standard metformin (2 μmol) applied on the wound daily till the scabs fell off. Results All treatments enhanced the rate of formation of granulation tissue and wound contraction. All treated rats showed lower blood glucose levels compared with their 1st-day values and significantly lower blood glucose levels when compared with the Aged Control rats. A significant restoration of the aging-depleted L-hydroxyproline, hexosamine, ascorbic acid, PDGF, AMPK, and mTOR levels, and attenuation of the aging-elevated IL-6 and TNF-α levels was elicited by all treatments. The treatments significantly restored the aging-depleted endogenous antioxidants. The Nishamalaki combination treatment of the oral extract and topical gel displayed a better wound-healing effect than the oral treatment alone. The histopathological studies on skin ulceration, hair follicles, granulation tissue, and collagen fiber formation of the wound tissues corroborated the biochemical findings. Conclusion Curcumin and other antioxidant polyphenolic components of Nishamalaki may be responsible for its wound-healing effect. For the first time, the present study has investigated the action of PDGF, AMPK, and mTOR on cutaneous wounds. They seem to be acting together to promote wound healing and repair. Graphical Abstrac

A randomized, controlled, comparative, proof-of-concept study to evaluate the efficacy and safety of Nisha-Amalaki capsules in prediabetic patients for preventing progression to diabetes

Background: Prediabetes is an intermediate state of hyperglycemia, which acts as a precursor to Diabetes mellitus if left untreated. Nisha (Curcuma longa) and Amalaki (Emblica officinalis) combination has been advocated as drugs of choice to treat the early manifestations of Diabetes mellitus. Objective: This prospective, randomized, single-blind, placebo-controlled, comparative study was planned to assess the efficacy and safety of Nisha-Amalaki capsules in preventing progression to Diabetes mellitus in prediabetic patients when administered for 6 months. Methods: The study was conducted on prediabetic participants randomized to receive either Nisha-Amalaki (500 mg) or placebo one capsule twice a day for six months. The effect of study medications on IDRS (Indian Diabetes Risk Score), BMI (Body Mass Index), blood sugar, serum insulin, HOMA-IR (Homeostasis Model Assessment-Estimated Insulin Resistance), HbA1c (glycated hemoglobin), oxidative markers, Ayurvedic symptoms and Quality of Life (QoL) scores was assessed at regular intervals. Results: 58 of the 62 participants enrolled completed the study. Significant fall in IDRS score [p < 0.001], BMI [p < 0.001], fasting, and 2 h post-OGTT sugar, insulin, HbA1c, HOMA-IR, and oxidative stress markers [p < 0.001] was observed in patients receiving Nisha-Amalaki at 6 months. Ayurvedic symptoms and QoL scores also improved at 6 months in the treatment group. Conclusion: Treatment with Nisha-Amalaki capsules improved all study parameters including insulin sensitivity at 6 months as compared to placebo in prediabetic patients. Thus Nisha-Amalaki should be considered as prophylactic therapy in prediabetics to delay progression to diabetes