Skin delivery of resveratrol encapsulated lipidic formulation for melanoma chemoprevention.

Objective: An unmet need for patient friendly products can be achieved with novel, biocompatible lipidic formulations which encapsulate and prolong release of medicaments. The aim of this study was to develop a commercially scalable resveratrol-loaded solid-lipid microparticulate (SLM) topical gel for melanoma chemoprevention. Methods: Preformulation studies were conducted and drug-excipient interactions examined using infra-red spectroscopy and differential scanning calorimetry (DSC). Resveratrol-loaded SLM topical gel was prepared and evaluated by in vitro and in vivo parameters. Results: Spherical microparticles of 2.98 µm average size were obtained and DSC thermograms provide evidence of trans-resveratrol encapsulation. In vitro and ex vivo drug diffusion studies revealed sustained release profiles. Optimised SLM gel provides optimum antioxidant, tyrosinase inhibition, cytotoxicity in B16F10 melanoma cell line and apoptosis efficacy. In vivo studies on C57BL mice exhibit significant tumour reduction. Conclusion: Promising role of trans-resveratrol-loaded SLM topical gel in melanoma chemoprevention is proven.

Mucosal and blood-brain barrier transport kinetics of the plant N-alkylamide spilanthol using in vitro and in vivo models.

BACKGROUND: N-alkylamides (NAAs) are a large group of secondary metabolites occurring in more than 25 plant families which are often used in traditional medicine. A prominent active NAA is spilanthol. The general goal was to quantitatively investigate the gut mucosa and blood-brain barrier (BBB) permeability pharmacokinetic properties of spilanthol. METHODS: Spilanthes acmella (L.) L. extracts, as well as purified spilanthol were used to investigate (1) the permeation of spilanthol through a Caco-2 cell monolayer in vitro, (2) the absorption from the intestinal lumen after oral administration to rats, and (3) the permeation through the BBB in mice after intravenous injection. Quantification of spilanthol was performed using a validated bio-analytical UPLC-MS(2) method. RESULTS: Spilanthol was able to cross the Caco-2 cell monolayer in vitro from the apical-to-basolateral side and from the basolateral-to-apical side with apparent permeability coefficients Papp between 5.2 · 10(-5) and 10.2 · 10(-5) cm/h. This in vitro permeability was confirmed by the in vivo intestinal absorption in rats after oral administration, where an elimination rate constant ke of 0.6 h(-1) was obtained. Furthermore, once present in the systemic circulation, spilanthol rapidly penetrated the blood-brain barrier: a highly significant influx of spilanthol into the brains was observed with a unidirectional influx rate constant K1 of 796 µl/(g · min). CONCLUSIONS: Spilanthol shows a high intestinal absorption from the gut into the systemic circulation, as well as a high BBB permeation rate from the blood into the brain.

Efficacy and acceptability of pomegranate effervescent granules in patients suffering from acid peptic disorders.

CONTEXT: Acid peptic disorders. AIMS: This study aimed to assess the efficacy and acceptability of pomegranate effervescent granules (PEGs) in dyspeptic patients. SETTINGS AND DESIGN: It was a single-arm, open-labeled prospective multicentric clinical study, done at 3 centers: Vishwanand Kendra, Pune; Bharati Ayurved Hospital, Bharati Vidyapeeth, Pune, and M. A. Podar Medical Ayurved Hospital, Mumbai. The co-ordinating site was Interactive Research School for Health Affairs, Bharati Vidyapeeth, Pune. MATERIALS AND METHODS: The granules, prepared from peel extract of pomegranate, were made available in sachets of 2.5 g with dose of, 1 sachet dissolved in 200 ml (1 cup) of water, twice a day after meals for 28 days. Gastrointestinal Symptom Rating Scale (GSRS) scores to assess symptoms of acid peptic disorders at day 0, 15, and 29 along with the taste of formulation were the main study outcomes. STATISTICAL ANALYSIS USED: Parametric data, presented as mean ± standard deviation, were analyzed using paired t-test, while nonparametric data presented as median (range) was analyzed using Wilcoxon rank-sum test. Categorical data were analyzed using Chi-square test. RESULTS: The median GSRS score reduced from 14 on day 0-10 and then 5 on day 15 and day 29, respectively, with statistical significance. The formulation was found to taste good by ~80% of patients, while ~20% reported it to be palatable and none found it to be bad in taste. CONCLUSION: PEGs proved to be palatable, patient-friendly, safe, and efficacious in resolving symptoms of dyspepsia in acid peptic disorders. CTRI Registration: The trial was registered retrospectively in the Clinical Registry of India [CTRI/2017/07/008999].

Isolation, characterization and quantitative HPLC-DAD analysis of components of charantin from fruits of Momordica charantia.

Charantin, a steroidal glycoside, exists as a mixture of stigmasterol glucoside (STG) and ß-sitosterol glucoside (BSG) in the fruits of Momordica charantia. Charantin has anti-diabetic activity comparable to insulin. The present work discusses a method for separation of components of charantin namely STG and BSG by simple extraction technique followed by preparative HPLC. The identity of separated components was established by chromatographic as well as spectral techniques. Also reversed phase HPLC-DAD method was developed and validated for estimation of STG and BSG present in fruits of Momordica charantia. The method used C18 column (75 mm × 4.6 mm, 3.5 µm) as stationary phase and methanol: water (98:02, v/v) as mobile phase. Retention times of STG and BSG were found to be 10.707 min and 11.870 min, respectively. The validated method was applied to evaluate content of these components in different extracts and some commercial herbal formulations containing fruits of Momordica charantia.

Phytochemical Markers: Classification, Applications and Isolation.

BACKGROUND: There has been aroused demand for herbal drugs/products worldwide because of their fewer side effects as compared to synthetic drugs. The major obstacle in the global acceptance of herbal products is the lack of proper standardization technique. METHODS: Various test procedures have been used for authentication and quality control of botanicals among which marker based standardization has attained more attention. The major challenge faced by phytochemist is to select appropriate phytochemical marker for quality control of herbal drugs. Phytochemical markers used for standardization must be of known purity. Phytochemical markers which are not commercially available have to be isolated from respective medicinal plants. Various chromatographic techniques are reported for the purification of phytomarkers from plants. A comprehensive report on different purification techniques of isolation of phytochemical markers through in-depth review of scientific literature is required. CONCLUSION: This article highlights various classifications of phytochemical markers along with their applications in standardization of herbal drugs and various classical and modern analytical techniques for their isolation.

Advances in encapsulated dermal formulations in chemoprevention of melanoma: An overview.

BACKGROUND: The three forms of skin cancer are cutaneous malignant melanoma, basal cell carcinoma, and squamous cell carcinoma. Melanoma skin cancer is an aggressive type and one of the most chemotherapy-resistant malignancies. Conventional topical products are beset with limitations, leading to lower efficacy. There is a growing need to develop topical formulations encapsulated in polymeric and lipid nanoparticles, nanoemulsions, dendrimers, and liposomes exhibiting enhanced skin penetration and longer skin retention leading to better efficacy. OBJECTIVE: The objective of this article is the screening of reported novel drug encapsulated delivery systems effective topically in melanoma chemoprevention. AIM: The scope of this work is to provide an overview pertaining to the development and evaluation of three exemplary drug delivery systems (DDS), namely vesicular, particulate, and specialized emulsions. METHODS: Topical drug delivery approaches targeting skin cancer have been reviewed and discussed. The focal point of the article is presentation of insights from published studies. RESULTS: This review focuses on the novel delivery systems in chemoprevention of melanoma with discussion highlighting on advances in topical delivery. CONCLUSION: Literature indicates that drug-loaded encapsulated topical formulations when compared with conventional dosage forms for skin cancer treatment exhibit greater efficacy and provide benefits like extended drug release, protection of the active ingredient against degradation, and lower skin irritation. Incorporation of phytoconstituents in newer delivery systems will be the way forward for improved topical chemoprevention strategy in melanoma. This has raised hope in making dermal therapy more useful and acceptable.

Ayurvedic polyherbal combination (PDBT) for prediabetes: A randomized double blind placebo controlled study.

BACKGROUND: Increasing prevalence of type 2 diabetes mellitus (DM) has become alarming, burdening health care systems throughout the world. Prediabetes is an intermediate step before manifestation of full blown DM. Effective intervention at this step would help stop/slow progression to DM. OBJECTIVE: This study aimed at use of a polyherbal combination (PDBT - constituted of Tinospora cordifolia, Pterocarpus marsupium, Gymnema sylvestre, Zingiber officinale and Momordica charantia) along with life style modification compared to a placebo in prevention of DM among prediabetic individuals. MATERIALS AND METHODS: The study was a double blinded, placebo controlled randomized clinical trial. Participants were divided in to a group on PDBT and life style management (LSM) and second on placebo and LSM. Participants in the intervention group received 2 gm/day of PDBT. All participants received the intervention for a period of 6 months. RESULTS: One hundred and fourteen participants were enrolled in the study, 57 each in intervention and control group. At the end of the study, 8 participants from the intervention group, compared to 15 participants in the control group had converted to DM. There was a 47% risk reduction in the intervention group. Participants in the intervention group showed statistically significant decrease in their blood glucose level (fasting and PP), HbA1c, fasting serum insulin and HOMA-IR values. There was no significant change in BMI. No adverse effects were reported by any participants. CONCLUSION: PDBT along with LSM in prediabetic participants was associated with reduction in conversion to DM than placebo along with LSM without any adverse effects.

Enhanced HPLC-DAD Method for Fast Determination of Quercetin-3-O-ß-d-Glucoside in Extracts and Polyherbal Formulations Containing Azadirachta indica-Optimization and Validation.

Azadirachta indica has been used for its medicinal properties since time immemorial. Herbal medicines which are prepared using this medicinal tree are utilized to treat various diseases and disorders. No reports are available for marker-based standardization of these herbal medicines prepared from leaves of A. indica. Also existing HPLC methods for determination quercetin-3-O-ß-d-glucoside are time consuming. There is an obvious need for development of new HPLC method for quantification of quercetin-3-O-ß-d-glucoside which is fast enough to carry out analysis in stipulated time period. This article deals with the development, optimization and validation of fast HPLC-DAD method for the determination of quercetin-3-O-ß-d-glucoside in extracts containing A. indica for its successive application for marker-based standardization of herbal formulations containing A. indica. The retention time of quercetin-3-O-ß-d-glucoside was 11.213 min. The method was found to be linear in the range of 4.0-60 µg mL-1. Limit of detection and limit of quantitation of the proposed method were found to be 1.33 and 4.0 µg mL-1, respectively. The mean recoveries were found to be within 93.53-103.75%. The method can be used as quality control tool for routine analysis of herbal extracts and formulations containing A. indicia.

Comparative efficacy of two polyherbal creams with framycetin sulfate on diabetic wound model in rats.

BACKGROUND: Diabetes mellitus is one of the metabolic disorders that impede normal steps of wound healing process. Worldwide, 15% of the 200 million diabetics suffer from diabetic wounds. Diabetic complications, such as foot ulcer, impose major public health burdens worldwide. OBJECTIVE: The present study was carried out to evaluate comparative efficacy of polyherbal creams with framycetin sulfate cream on diabetic rats using incision and excision wound models. MATERIALS AND METHODS: Alloxan (120 mg/kg, intraperitoneal) induced diabetic rat models (incision and excision models) were used to evaluate wound healing effect of cream A, B, and framycetin sulfate. Cream A and B were applied for a period of 10 and 20 days for incision and excision wound models, respectively. Incision wound model was used to assess the effect on breaking strength. Wound contraction and epithelialization period were measured using excision wound model. The data were analyzed by one-way ANOVA followed by Bonferroni post-test. RESULTS: Tensile strength of the animals treated with cream B (941.66 ± 15.36) was found to be significantly greater (P < 0.001) as compared to tensile strength of the animals treated with cream A (825 ± 22.36). Wound treated with cream B was found to heal significantly (P < 0.001) faster (day 17) as compared to wounds treated with framycetin sulfate (day 21). CONCLUSIONS: Cream B was found to be more effective wound healing agent than cream A and framycetin sulfate cream in treating diabetic wounds.

Quantitative In Vitro and In Vivo Evaluation of Intestinal and Blood-Brain Barrier Transport Kinetics of the Plant N-Alkylamide Pellitorine.

Objective. To evaluate the gut mucosa and blood-brain barrier (BBB) pharmacokinetic permeability properties of the plant N-alkylamide pellitorine. Methods. Pure pellitorine and an Anacyclus pyrethrum extract were used to investigate the permeation of pellitorine through (1) a Caco-2 cell monolayer, (2) the rat gut after oral administration, and (3) the BBB in mice after intravenous and intracerebroventricular administration. A validated bioanalytical UPLC-MS(2) method was used to quantify pellitorine. Results. Pellitorine was able to cross the Caco-2 cell monolayer from the apical-to-basolateral and from the basolateral-to-apical side with apparent permeability coefficients between 0.6 · 10(-5) and 4.8 · 10(-5) cm/h and between 0.3 · 10(-5) and 5.8 · 10(-5) cm/h, respectively. In rats, a serum elimination rate constant of 0.3 h(-1) was obtained. Intravenous injection of pellitorine in mice resulted in a rapid and high permeation of pellitorine through the BBB with a unidirectional influx rate constant of 153 µL/(g·min). In particular, 97% of pellitorine reached the brain tissue, while only 3% remained in the brain capillaries. An efflux transfer constant of 0.05 min(-1) was obtained. Conclusion. Pellitorine shows a good gut permeation and rapidly permeates the BBB once in the blood, indicating a possible role in the treatment of central nervous system diseases.

Ayurvedic polyherbal combination (PDBT) for prediabetes: A randomized double blind placebo controlled study

Background: Increasing prevalence of type 2 diabetes mellitus (DM) has become alarming, burdeninghealth care systems throughout the world. Prediabetes is an intermediate step before manifestation offull blown DM. Effective intervention at this step would help stop/slow progression to DM.Objective: This study aimed at use of a polyherbal combination (PDBT e constituted of Tinospora cordifolia, Pterocarpus marsupium, Gymnema sylvestre, Zingiber officinale and Momordica charantia) alongwith life style modification compared to a placebo in prevention of DM among prediabetic individuals.Materials and Methods: The study was a double blinded, placebo controlled randomized clinical trial.Participants were divided in to a group on PDBT and life style management (LSM) and second on placeboand LSM. Participants in the intervention group received 2 gm/day of PDBT. All participants received theintervention for a period of 6 months.Results: One hundred and fourteen participants were enrolled in the study, 57 each in intervention andcontrol group. At the end of the study, 8 participants from the intervention group, compared to 15participants in the control group had converted to DM. There was a 47% risk reduction in the interventiongroup. Participants in the intervention group showed statistically significant decrease in their bloodglucose level (fasting and PP), HbA1c, fasting serum insulin and HOMA-IR values. There was no significant change in BMI. No adverse effects were reported by any participants.Conclusion: PDBT along with LSM in prediabetic participants was associated with reduction in conversion to DM than placebo along with LSM without any adverse effects.© 2018 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services byElsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Safety Profile of a Polyherbal Formulation (Gynocare capsules) in Female Rats by Subchronic Oral Toxicity Study.

Gynocare capsules, is a polyherbal formulation, are used as uterine tonic and for treating gynaecological ailments like infertility, leucorrhea, and menstrual disorders. The formulation contains ingredients of herbal origin, such as, extracts of Ashoka, Vasaka, Durva, Chandan, Musk, and so on. It was evaluated for its safety at the therapeutic dose level by a repeated dose oral toxicity study in albino Wistar rats. The herbal formulation was administered orally at a therapeutic dose of 100 mg/kg/day, for 90 days. All animals were monitored daily for their health status and signs of abnormalities. The body weight, water consumption, and food intake were measured once weekly. At the end of the experimental period, various hematological and biochemical parameters were estimated and histopathologies of selected organs were conducted. The study resulted from the long-term oral administration of Gynocare capsules (100 mg/kg), did not cause any relevant signs of toxicity nor significant changes in the physical, hematological and biochemical parameters. However, statistically significant differences were seen in the relative organ weights of adrenal gland, ovary, and serum creatinine levels. The reduction in ovary weight revealed the possibility of the drug targeting the ovary. Moreover, no pathological features were identified in the treated group as monitored by the histopathological analysis of the internal organs. The study established that Gynocare capsules at the dose given (100 mg/kg) did not induce any remarkable or significant toxic effects, indicating that it was safe in rats following oral administration for 90 consecutive days.

Contraceptive efficacy and safety of HerbOshield™ vaginal gel in rats.

BACKGROUND: Spermicides represent one of the methods of contraception. The synthetic agents available as spermicides produce severe side effects. Hence, there is a need to replace these agents with safe and effective agents such as plant-based contraceptive agents. STUDY DESIGN: The objective of the present study was to develop and evaluate a stable, safe, effective and easily acceptable contraceptive delivery system containing herbal drug. Efforts were made to evaluate the contraceptive potential of the hydroalcoholic extract from the seeds of Annona squamosa Linn. and the vaginal gel HerbOshield™ containing the extract. RESULTS: Spermicidal effect was evaluated in vitro using healthy human spermatozoa and in vivo in rats. The in vitro results demonstrated that HerbOshield™ vaginal gel is an effective spermicide. At a 100-mg/mL dose, complete immobilization of human spermatozoa was observed within 20 s. None of the treated animals conceived, indicating 100% contraceptive effect as compared to Gynol II, a nonoxynol-9-containing marketed formulation, which showed only 67% contraceptive effect in vivo. HerbOshield™ vaginal gel was found to be safe in animals during a 14-day toxicity study. CONCLUSIONS: HerbOshield™ vaginal gel was found to be safe and effective in rats and could be developed as a potential vaginal contraceptive for future use in humans.

Immunological studies on the aerial roots of the Indian banyan.

The aqueous extract of the aerial roots the Indian Banyan, Ficus benghalensis L. (Family: Moraceae) was evaluated for its effect on both specific and non-specific immunity. This extract exhibited a significant increase in percentage phagocytosis by human neutrophils in the in vitro tests. It exhibited promising immunostimulant activity at doses of 50, 100, 200 and 400 mg/kg body weight in SRBC induced hypersensitivity reaction and hemagglutination reaction in rats. The aqueous extract was found to stimulate the cell mediated and antibody mediated immune responses.

Antimicrobial activity of ayurvedic tablet "hadrabi".

The Ethanolic extract of "Hadrabi" powder was tested for antimicrobial activites against gram positive organisms-Staphylococus aureus, Bacillus subtilis, Clostridium perfringens and gram negative organisms-Pseudomonas aeruginosa, Salmonella paratyphi -B, Escherichia coli & Klebsiella pneumoniae Significant antimicrobial activity of the extract was found in this study at the dose of 1250 mg.