Preparation and Characterization of Silymarin Gel: A Novel Topical Mucoadhesive Formulation for Potential Applicability in Oral Pathologies.

Silybum marianum has been used for centuries by herbalists and physicians to treat different forms of liver diseases. It contains flavonoid, which has antioxidant, anti-inflammatory, antifibrotic and anticancer properties. The objective of this research was to develop a silymarin-based mucoadhesive gel for prolonged release in oral mucosa and to evaluate the same by using in vitro drug release kinetic models and ex vivo methods for drug permeation using chicken buccal mucosa. The mucoadhesive gel was formulated in different trials by varying the concentration of silymarin and polymer. Out of 10 formulation trials, the F10 optimized trial was characterized for in vitro physicochemical parameters such as pH, homogeneity, viscosity, stability, drug content, in vitro drug release, in vitro antioxidant assay and ex vivo permeation study. Trial 10 was chosen as the best trial formulation among the other trials and was marked as an optimal trial. The physicochemical properties observed were pH to be 6.4 ± 0.01, the gel free of lumps, spreadability of 23.75 ± 0.03 and drug content of 32.77 ± 0.20 mg/g. It had no physiological changes such as color shift or fluid exudate segregation after 6 months of storage at room temperature. In vitro drug release established the presence of a non-fickian mechanism and demonstrated dose-dependent antioxidant activity. Ex vivo findings indicated 21.97 ± 0.18% release, proving that the gel can permeate through the oral mucosal membrane. Our future research will concentrate on expanding the therapeutic scope by developing the formulation trial F10 to a nanoformulation and conducting clinical trials for its potential use in various oral diseases.

Traditional medicine herbs as natural product matrices in cancer chemoprevention: A trans pharmacological perspective (scoping review).

Emerging evidence on molecular biology related to tumors, inflammation, and immunity, highlights their architectural commonality shifting cancer treatment paradigms toward more economical prevention than treatment. Statistical surveys reveal exponentially growing herbal drug supplementation in cancer worldwide as vast pre-clinical and clinical data unravel their multi-mechanistic pharmacology. The integrative oncological approach calls for more "holistic" principles to be amalgamated into cancer care. New cancer drug development from herbs need not be limited by the archetypal 'RCT-Standardization' bottlenecks. Based on comprehensive literature scoping as per Prisma-ScR guidelines, we herein concurrently reviewed evidence-based research reports of selected Indian Traditional Medicine (ITM) herbs of anticancer repute in parallel with their holistic therapeutics; a rationalistic exploration of ITM's scientific genre. Their synergy effect on cancer revisited using a trans-pharmacological approach validates ITM's seemingly simplistic health/disease equation model, showing a fresh new avenue for re-purposing whole herbal drug complexes in cancer management. Herbal drugs as per ITM are natural matrices whose dynamics of interaction in the etiopathology of cancer are conceptually and mechanistically integrative. Lateral perspective to the same as laid out in this review holds the key to their effectual development as more tangible cancer chemopreventives/new drug targets/leads if not as new pharmacological tools.

Effect of turmeric supplementation on the pharmacokinetics of paclitaxel in breast cancer patients: A study with population pharmacokinetics approach.

Turmeric is one of the most used herbal supplements among cancer patients. It reportedly modulates the function of CYP450 enzymes and drug transporters. This study investigates the effect of turmeric on the pharmacokinetics of paclitaxel in breast cancer patients. This is a prospective longitudinal study with 60 breast cancer patients on treatment with single-agent paclitaxel and turmeric. The patients were followed up for two consecutive chemotherapy cycles, and their blood samples were collected, first without turmeric (first cycle) and the next after a 21-day concomitant administration of 2 g/day turmeric (second cycle). Plasma samples were quantified for paclitaxel concentration using High Performance Liquid Chromatograph with UV detector (HPLC-UV) method. The sparse concentration-time data of paclitaxel were subjected to population pharmacokinetic modeling, and then noncompartmental analysis (NCA) was performed on the simulated data to estimate the pharmacokinetic parameters of paclitaxel, before and after turmeric supplementation, for comparisons. The population pharmacokinetic parameters of paclitaxel differed from before to after turmeric supplementation. NCA of simulated concentration-time profiles showed a statistically significant reduction of 7.7% and 12.1% in AUCinf and Cmax, respectively. Given the small magnitude of the changes in pharmacokinetic parameters, the observed changes are not clinically relevant. Thereby, turmeric at the recommended dose can be combined safely with paclitaxel.

Challenges and Prospects of Development of Herbal Biomaterial Based Ethical Wound Care Products-A Scoping Review.

Total wound care is an unmet therapeutic need considering the morbidity and mortality associated with the rising prevalence of nonhealing/chronic wounds. Current wound management fails to address all aspects/types of wounds despite the availability of scores of traditional and modern, investigational products. Traditional medicine drugs of wound healing repute validated to target multiple biological pathways and key events in the mammalian wound healing cascade, reportedly affecting wound healing phases. Advances in the development of biocomposite matrices and their analytical characterization warrant a relook at consolidating time-tested wound healing properties of herbal bioactives for prospective development as ethical wound care products. Aside from the bottlenecks of their multiconstituent profiling and clinical trial data generation, regulatory hurdles also cloister any systematic attempts at their re-engineering into clinical deliverables. In the context of national policy changes to bring in totally indigenous solutions, countries with a huge knowledge/material resource on wound healing bioactives need to essentially facilitate the same.

Turmeric supplementation improves the quality of life and hematological parameters in breast cancer patients on paclitaxel chemotherapy: A case series.

BACKGROUND: and purpose: Phytochemicals are proven to be effective in targeting numerous signaling pathways in cancer. Utilizing plant-based support in combination with currently approved chemotherapeutic strategies might prove a feasible method to improve therapeutic outcomes in cancer patients. The present study aimed to estimate the effect of turmeric supplementation on quality of life (QoL) and hematological parameters in breast cancer patients on Paclitaxel chemotherapy. MATERIALS AND METHODS: The present study is a prospective consecutive case series with 60 participants. QoL was assessed using a standard questionnaire and hematological parameters were recorded from the patients' hospital records. RESULTS: Turmeric supplementation for 21 days resulted in clinically relevant and statistically significant improvement in global health status, symptom scores (fatigue, nausea, vomiting, pain, appetite loss, insomnia), and hematological parameters. CONCLUSION: The study findings show that turmeric supplementation improved QoL, brought about symptom palliation and increased hematological parameters in breast cancer patients.

Fabrication and characterization of herbal drug enriched Guar galactomannan based nanofibrous mats seeded with GMSC's for wound healing applications.

Electrospun nanofibrous Guar gum/PVA based scaffold matrix incorporated with standardized extracts of four traditional medicinal plants of wound healing repute namely - Acalypha indica (A.i), Aristolochia bracteolata (A.b), Lawsonia inermis (L.i) and Thespesia populnea (T.p) was developed. Combinatorial ratio optimization of the extracts subject to their impact on nanofibre morphology, thermal and swelling stability resulted in a 4:4:1:1 blend of A.i, A.b, T.p and L.i at 20% of the total weight of the polymer mix. Dermal toxicity studies on female wistar rats established the nontoxicity of the generated Scaffold/Dressing. Cutaneous wound healing ability of Mesenchymal Stem Cells (MSC's) is well characterized to amplify their delivery and efficacy at the wound site. Apart from ease of accessibility, increased immune modulation of Gingival MSC's is their clear merit relative to those conventionally sourced from adipose tissues and bone marrow. A population of cells were isolated from discarded sample of human gingiva, following standard procedures and characterized as per minimal criteria as described by International Society for Cellular Therapy's (ISCT). The Cytocompatibility and proliferation of GMSC's were evaluated by MTT and Calcein AM assay demonstrating the viability of the seeded GMSC's up to 6 days. In vivo efficacy of the scaffold with and without GMSC's showed complete restoration of the tissue with minimal scarring. This investigation thus generated an herb drug enriched nanofibrous mat as a dressing and also a skin like scaffold with GMSC's, integrating the biological and technological benefits of herbal medicine and stem cell therapy respectively for skin regenerative applications.

Transdifferentiation of human gingival mesenchymal stem cells into functional keratinocytes by Acalypha indica in three-dimensional microenvironment.

Gingival tissue is reportedly a promising, easily accessible, abundant resource of mesenchymal stem cells (MSC) for use in various tissue engineering strategies. Human gingival MSC (HGMSCs) were successfully isolated from gingival tissue and characterized. To analyze in a two-dimensional form, HGMSCs were cultured with basal medium and induced with 25 µg/ml of Acalypha indica. Quantitative real-time polymerase chain reaction (qPCR) and western blot analysis showed the presence of keratinocyte-specific markers, including cytokeratin-5 and involucrin. To further assess its capability for stratification akin to human keratinocytes, HGMSCs were encapsulated in a HyStem® -HP Cell Culture Scaffold Kit and cultured in the presence of A. indica. Calcein AM staining indicated that the HyStem® -HP Scaffold Kit has excellent biocompatibility. Immunofluorescence and qPCR analysis revealed the presence of keratinocyte-specific markers. The study concluded that the three-dimensional microenvironment is a novel method for inducing epidermal differentiation of HGMSCs to engineer epidermal substitutes with the help of A. indica, which provides an alternative strategy for skin tissue engineering.

Data set on the characterization of the phytoestrogenic extract and isolated compounds of the roots of Inula racemosa Hook F (Asteraceae).

The data presented in this article are related to the research article entitled ' Phyto estrogenic effect of Inula racemosa Hook. f - A cardio protective root drug in traditional medicine, (Mangathayaru K, Divya R, Srivani T et al., 2018) [1]. It describes the characterization details of the root extract and the compounds isolated from them that were shown to be phytoestrogenic in vivo and in vitro respectively.

Phytoestrogenic effect of Inula racemosa Hook f - A cardioprotective root drug in traditional medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Roots of Inula racemosa are used as a cardio protective in Ayurveda in India, being prescribed as a medicine for precordial chest pain, cough and dyspnoea, both singly and as a poly herbal. AIM: Evaluation of Phytoestrogenic activity of the root extracts of Inula racemosa and compounds isolated therefrom in vivo, in silico and in vitro. MATERIALS AND METHODS: Alcohol (IrA) and hexane (IrH) extracts characterized by HPTLC/GC-MS analysis respectively and processed for compound isolation were evaluated for estrogenic activity (100 & 250mg/kg bw) by the Immature rat uterotrophic assay using ethinylestradiol (EE -30µg/kg bw) as standard drug. Alantolactone (ALT), Isoalantolactone (IALT) and Stigmasterolglucoside (SG) isolated from the extracts were characterized and screened in silico for ERα, ERß binding affinity, assessed in vitro for growth modulatory effects on MCF-7 cells by MTT assay and cell cycle distribution analysis using Flow cytometry. RT-PCR analysis evaluated the mRNA expression of pS2 in these cells post exposure to ALT, IALT and SG. RESULTS: In the IrA treated groups there has been a statistically significant increase (P < 0.05) in absolute and normalised uterine weight, uterine diameter, endometrial thickness, luminal epithelial cell height,diameter of ovary and in the number of primary and secondary ovarian follicles relative to untreated controls. Presence of ciliated epithelial cells in the oviduct, elevated number of early growing follicles characterized by an increased oocyte diameter, and signs of vascularization in the cortex of ovarian sections in this group relative to EE treated group are indicative of pervasive activation of follicular growth and initiation. Virtual docking demonstrated ERα affinity for IALT, ERß affinity for ALT, while SG showed a high binding affinity to both with a relatively greater ERß binding affinity. Dose dependent decrease in cell viability mediated by IALT and SG in the MTT assay is corroborated by a statistically significant increase (p < 0.05) in sub G0-G1 cells by SG at 200 and 400µM in cell cycle analysis and there has been an induction of pS2 by IALT and SG in the ER regulated MCF-7 cells. CONCLUSIONS: Demonstration of classical morphological changes induced by estrogen stimulation mediated by IrA in vivo at both the tested doses, isolation of the antioxidant SG from IrA and its dose dependent growth inhibitory effect on estrogen sensitive MCF-7 cells through apoptotic induction and an up regulation of pS2 are suggestive of an anti-estrogenic effect through estrogen receptor binding affinity, typical of phytoestrogens that bind to ER but do not elicit a full estrogenic response. The observed estrogenic effect of IrA suggests a multi mechanistic molecular action involving antioxidant as well as redox signalling pathways acting in consonance with their anti-estrogenic effects owing to the weak estrogen like competitive receptor binding of SG.

Osteogenic differentiation of human gingival mesenchymal stem cells by Aristolochia bracteolata supplementation through enhanced Runx2 expression.

The phenotypic characteristics of human gingival derived mesenchymal stem cells (HGMSCs) on induction with total methanol extract of Aristolochia bracteolata have been evaluated. HGMSCs were cultured in control and two different induction medium: Control medium (basal medium), OM1 (Standard induction medium), and OM2 (100 µg/ml of A. bracteolata). Osteogenic differentiation of the cultured cells was assessed by studying the calcium deposition and osteoblastic gene expression. OM2 medium showed an enhanced osteogenic differentiation potential than OM1 as measured by increased calcium deposition and elevated expression of Runx2, osteopontin, osteonectin, osteocalcin, Collagen type I, and ALP levels in comparison with OM1 differentiated cells. We conclude that at 100 µg/ml A. bracteolata has induced HGMSC differentiation into osteogenic lineage consequent to enhanced Runx2 expression and related osteogenic genes.

Isolation and evaluation of cytogenetic effect of Brahmi saponins on cultured human lymphocytes exposed in vitro.

Major saponins of Brahmi (Bacopa monniera, Fam: Scrophulariaceae) - bacosides A and B - were isolated from the total methanol extract and characterised based on melting point, TLC, IR, (1)H NMR and (13)C NMR. They were evaluated for their in vitro cytogenetic effects on human peripheral blood lymphocytes by chromosomal aberration (CA) assay and sister chromatid exchange (SCE) assay. The frequency of chromatid type aberrations and reciprocal interchanges between sister chromatids in the treated cells was scored in comparison to the untreated control. At 30 µg/mL dose, bacoside A showed a statistically significant increase in the frequency of both CA and SCE and bacoside B showed an increase only in SCE. Our report of the genotoxicity of the saponins is significant in view of the reports of anticancer activity of Brahmi extracts.