In vitro and in silico analysis proving DPP4 inhibition and diabetes-associated gene network modulation by a polyherbal formulation: Nisakathakadi Kashaya.

Dipeptidyl-peptidase IV (DPP4) inhibitors are an important class of anti-diabetic drugs recognised for their systemic biological actions. Polyherbal preparations like Ayurveda formulations are considered to be ideal sources for discovering novel DPP4 inhibitors owing to their rich phytochemical composition. The current study reports the DPP4 inhibitory potential of a clinically established Ayurvedic anti-diabetic formulation Nisakathakadi Kashaya (NK) using in vitro assay and substantiates it by identifying potential bioactives responsible for DPP4 inhibition using computational biology tools. NK showed a dose-dependent DPP4 inhibition with an IC50 of 2.06 µg GAE/mL, and the molecular docking and simulation studies showed three compounds, namely Terchebin, Locaracemoside B and 1,2,4,6 Tetra o Galloyl Beta D Glucose having stable interactions with DPP4 similar to the standard drug Vildagliptin. Further, for the reason that polyherbal formulations exert a network pharmacology mode of action, in silico analysis was carried out to identify the other putative phytochemical-protein networks modulated by NK. The complex pharmacological network of the formulation was explored further using a subnetwork of diabetes proteins and their relationship with diabetes-associated comorbidities. A number of key targets like TNFα, TGFß1, SOD1, SOD2, AKT1, DPP4 and GLP1R were identified in the protein-protein interaction network that is vital to diabetic progression and complications. A combination of in vitro and in silico methods allowed us to prove the DPP4 inhibition potential of NK as well as provided insights into the possible pharmacological networking through which NK potentially exerts its systemic effect in diabetes management.Communicated by Ramaswamy H. Sarma.

De novo genome assembly and annotation of the medicinal plant Tinospora cordifolia (Willd.) Miers ex Hook. f. & Thom's.

Indian natural climbing shrub Tinospora cordifolia, often known as "Guduchi" and "Amrita," is a highly esteemed medicinal plant in the Indian system of medicine (ISM). It is a member of the Menispermaceae family which consists of a rich source of protein, micronutrients, and rich source of bioactive components which are used in treating various systemic diseases. The current study was designed to know the biological characterization of the plant genome and biosynthesis of plant metabolites essential for its medicinal applications. Tinospora cordifolia's complete genome was sequenced using Illumina HiSeq2500 sequencing technology. The draft genome was assembled through a de novo method. An integrative genome annotation approach was used to perform functional gene prediction. The pathway analysis was carried out using the KEGG database. The total genome size obtained after genome assembly was 894 Mb with an N50 of 9148 bp. The integrative annotation approach resulted in 35,111 protein-coding genes. In addition, genes responsible for the synthesis of syringin, a secondary metabolite found in plants, were identified. In comparison to the standard drug (dopamine, rasagiline, and selegiline), syringin's molecular docking exhibited a greater binding affinity from the range of - 4.3 to - 6.6 kcal/mol for all the targets of Parkinson's disease and for Alzheimer's targets; it has shown the maximum potency from the range of - 6.5 to - 7.4 kcal/mol with respect to the standard drug (donepezil, galantamine, and rivastigmine). This study provides the genomic information of Tinospora cordifolia which is helpful in understanding genomic insights and metabolic pathways connected to the corresponding plant genome and predicts the possible useful effect for the molecular characterization of therapeutic drugs.

De novo genome assembly and annotation of gall-forming medicinal plant Pistacia chinensis subsp. integerrima (J. L. Stewart ex Brandis) Rech. f.

Pistacia chinensis subsp. integerrima is one of the medicinal plants, well known for gall formation and popularly used in Ayurveda to treat various systemic diseases such as chronic disorders, respiratory problems, etc. P. integerrima genome characterization will aid in the study of Pistacia genes and pathways involved in therapeutic application. To understand the biological characteristics of this plant and to gain the genetic insight into the biosynthesis of its natural compounds, the whole genome of P. integerrima and its leaf transcriptome was sequenced using Illumina sequencing technology. The sequenced genome was functionally annotated, and gene prediction was performed with integrated genome annotation workflow. The pathway analysis was carried out using KEGG database. We obtained a draft genome assembly of 462 Mb with N50 16,145 bp. A total of 39,452 genes were found, and 18,492 of these contained RNA or protein evidence. We characterized the genes involved in biosynthetic pathways of different plant secondary metabolites such as flavonoids and terpenoids. Also, we identified miR397 and miR828 family noncoding RNA; which mainly targets the laccase (LCA) and MYB protein functioning respectively. Phylogeneic analysis showed that P. integerrima is genetically more closer to P. vera. In this study, we attempt to explore the whole genome information of P. integerrima which will provide a genomic insight in the future for omics studies as well as serves as valuable resource for the molecular characterization of medicinal compounds.

An 'Ayurveda-Biology' platform for integrative diabetes management.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes is a multifactorial disease with complex multi-organ-multi-target crosstalk in the body. Currently, the theoretical assumptions framing the diabetes management strategies are reductionist and largely focus on reducing hyperglycemia through targeted molecular drugs. While they effectively reduce hyperglycemia, they are inadequate to address the multifactorial etiopathology, chronicity and systemic complications of diabetes. Therefore, a holistic and systemic approach is essential for its successful management. We hypothesize an integrative diabetes management strategy, combining holistic principles of diabetes management with its molecular understandings, would be more appropriate to fill this gap. The holistic disease management principles of Ayurveda, the Indian system of medicine, can play a pivotal role in this context. This narrative review discusses the scope of a trans-disciplinary ' Ayurveda-Biology ' approach for deepening the holistic understanding of the pathophysiology of diabetes as well as designing novel integrative strategies for managing diabetes and restoring whole body glucose homeostasis. METHODOLOGY: The article analyses the Ayurveda scheme of diabetes management and correlates it with the molecular understanding of its pathophysiology and management. The sources of information used in this article include classical texts of Ayurveda , medical books, published research articles and scientific databases like PubMed, Google Scholar, Science-Direct, etc. RESULTS: While Ayurveda and modern biomedicine uses different epistemology and ontology for describing diabetes, both the systems recognize the central role of gut and gut derived factors in postprandial glucose disposal and whole body glucose homeostasis. Essentially, the principles of both Ayurveda and modern biomedicine overlap at a gut centred view of diabetes management; and Gastro-intestinal mediated glucose disposal , a holistic concept of glucose metabolism, is emerging as a converging node for designing innovative integrative diabetes management strategies. CONCLUSIONS: An integrative disease management strategy, combining holistic and reductionist perspectives of traditional medicine and biology respectively, would be the prerogative for successful management of diabetes. Creating an ' Ayurveda-Biology' knowledge framework integrating the patient centred holistic management principles of Ayurveda and the molecular approaches of modern biology can give better insights into the biology of whole body glucose homeostasis and offer novel strategies for cost effective, holistic and multi-targeted management of diabetes.

Need for comprehensive standardization strategies for marketed Ayurveda formulations.

Ayurveda is known for the use of poly-herbal formulations and multi-component therapeutics for the management of health and diseases. Several pharmaceutical companies are manufacturing and marketing different Ayurvedic formulations, prepared as per the classical texts and the regulatory standards. However, on a cursory glance, marked variations are observed amongst the same formulations manufactured by different companies. This raises questions on the quality standards. Drugs or formulations are expected to exert a desired biological activity at particular concentrations of their chemical constituents. The overall aim of drug standardization is to ensure the quality, efficacy and uniformity of the products, in terms of their chemical and biological properties, across the manufactures. In this article, the authors intend to open up a discussion on the need for comprehensive standardization strategies for marketed Ayurveda formulations taking Lodhrasavam (a classical Ayurveda preparation) as an example. Lodhrasavam procured from six reputed Ayurveda drug manufacturers showed significant variations in their sensorial, physico-chemical, chromatographic as well as biological properties. This is a matter of serious concern and need to be addressed effectively to derive better standardization strategies for Ayurvedic formulations.

Documentation of 'Plant Drugs' dispensed via local weekly shanties of Madurai City, India.

BACKGROUND: The Valaiyar (Moopanar) communities of Tamil Nadu are traditionally known for catching rats and snakes from the agricultural fields. Prior to independence, some of these families have faced socio-economic changes and chosen to become herbalists in Madurai city. They are mainly engaged in collecting and dispensing fresh and dried plant drugs in its 'natural form' at Tilagar tidal market of Madurai city. Their business is unique, because customers receive 'prescriptions' and 'plant drugs', unlike the conventional dispensaries. Their world view is: 'to cure the ailing in natural way'. OBJECTIVES: To document plant drugs collected and dispensed by some of the families belonging to Valaiyar (Moopanar) community in the Tilagar tidal market. MATERIALS AND METHODS: Ethnobotanical tools were employed to document various aspects of the practices including resource and knowledge base, medicinal uses, dosage, collection of herbarium and raw drug specimens. Integrative approach was adapted to document the trade dynamics. RESULTS: During the study, 133 medicinal plant species belonging to 50 families were documented. 71% of species were sourced from wild and non-forest areas. 272 simple and compound remedies were recorded. CONCLUSION: Local markets/shanties like these are 'Traditional Medicine (TM) health care services at door step'. They cater to local health care needs along with conventional system in a synergistic manner and provide adaptable, local solutions using local resources.

Ayurvedic anti-diabetic formulation Lodhrasavam inhibits alpha-amylase, alpha-glucosidase and suppresses adipogenic activity in vitro.

BACKGROUND: The patho-physiological cross-talk between diabetes and obesity is well established. However, the choices of drugs suitable for combined treatment of diabetes and obesity are limited. Integration of complementary and alternative medicines (CAMs), like Ayurveda, with modern medicine would be a promising strategy to fill this gap. The diagnostic principles of Ayurveda define obesity as one of the predisposing factors of Madhumeha (correlated as diabetes) and recommends specific formulations for managing obese-diabetes. Lodhrasavam is one such poly-herbal formulation prescribed for obese-diabetic patients. OBJECTIVES: The present study is an attempt to demonstrate the possible modes of action of Lodhrasavam, built on the hypothesis that the formulation can exert both anti-diabetic and anti-obesity actions. MATERIALS AND METHODS: Lodhrasavam, following simulated gastro-intestinal digestion, was monitored for inhibition of α-amylase, α-glucosidase (key digestive enzyme targets of anti-diabetic drugs) and adipogenesis using standard in vitro model systems. RESULTS: Lodhrasavam digest inhibited α-amylase (90%) and α-glucosidase (78%) activity as well as reduced the differentiation of 3T3-L1 fibroblasts to adipocytes. Upon fractionation, the enzyme inhibitory activity and anti-adipogenic activity of the digest were found distributed in different solvent fractions. This partly indicates a potential pharmacological networking of chemically and functionally diverse bioactive molecules in Lodhrasavam. CONCLUSION: The study provides a possible mode of action and an experimental support for the Ayurvedic use of Lodhrasavam for managing obese-diabetes. Generating scientific evidences and understanding the modes of action, in contemporary scientific language, would essentially help in expanding global acceptance of potentials of CAMs in the management of life style disorders.

Pomegranate Juice Enhances Healthy Lifespan in Drosophila melanogaster: An Exploratory Study.

Exploring innovative ways to ensure healthy aging of populations is a pre-requisite to contain rising healthcare costs. Scientific research into the principles and practices of traditional medicines can provide new insights and simple solutions to lead a healthy life. Rasayana is a dedicated branch of Ayurveda (an Indian medicine) that deals with methods to increase vitality and delay aging through the use of diet, herbal supplements, and other lifestyle practices. The life-span and health-span enhancing actions of the fruits of pomegranate (Punica granatum L.), a well-known Rasayana, were tested on Drosophila melanogaster (fruitfly) model. Supplementation of standard corn meal with 10% (v/v) pomegranate juice (PJ) extended the life-span of male and female flies by 18 and 8%, respectively. When male and female flies were mixed and reared together, there was 19% increase in the longevity of PJ fed flies, as assessed by MSD, the median survival day (24.8). MSD for control and resveratrol (RV) groups was at 20.8 and 23.1 days, respectively. A two-fold enhancement in fecundity, improved resistance to oxidative stress (H2O2 and paraquat induced) and to Candida albicans infection were observed in PJ fed flies. Further, the flies in the PJ fed group were physically active over an extended period of time, as assessed by the climbing assay. PJ thus outperformed both control and RV groups in the life-span and health-span parameters tested. This study provides the scope to explore the potential of PJ as a nutraceutical to improve health span and lifespan in human beings.

Plant-based Rasayana drugs from Ayurveda.

Rasayana tantra is one of the eight specialties of Ayurveda. It is a specialized practice in the form of rejuvenative recipes, dietary regimen, special health promoting behaviour and drugs. Properly administered Rasayana can bestow the human being with several benefits like longevity, memory, intelligence, freedom from diseases, youthful age, excellence of luster, complexion and voice, optimum strength of physique and sense organs, respectability and brilliance. Various types of plant based Rasayana recipes are mentioned in Ayurveda. Review of the current literature available on Rasayanas indicates that anti-oxidant and immunomodulation are the most studied activities of the Rasayana drugs. Querying in Pubmed database on Rasayanas reveals that single plants as well as poly herbal formulations have been researched on. This article reviews the basics of Rasayana therapy and the published research on different Rasayana drugs for specific health conditions. It also provides the possible directions for future research.