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Frontiers of disease biology started recognizing the importance of systems and network medicine approach for managing chronic disease like diabetes. Dipeptidyl-peptidase IV (DPP4) inhibitors are one such class of anti-diabetic drugs recognized for their systemic biological actions. Polyherbal preparations likeAyurvedaformulations are ideal for identifying novel DPP4 inhibitors having greater efficacy and safety profile. Additionally, expanding the research on the multitargeted mode of action of these polyherbal formulations can render novel insights into the complex biology of disease manifestations. The current study aims at identifying DPP4 inhibitory potential of a clinically established Ayurveda anti-diabetic formulationNisakathakadi Kashaya(NK) usingin vitroandin silicomethods as well as the modulation of diabetes associated gene network by NK. a. Standard enzyme inhibition assay was used to study the DPP4 inhibitory potential of NK, followed by bioinformatics and computational biology tools for identifying the potential bioactives and their molecular interactions involved in DPP4 inhibition. STITCH, CHEMBL and BindingDB databases were used for target mapping and depicting the multi-targeted network pharmacology interaction of NK and the formulation. EnrichR was used to depict a sub-network of diabetes proteins and their relationship with diabetes associated comorbidities. NK demonstrated a dose dependent DPP4 inhibition with an IC50of 2.06 μg GAE/mL. Molecular docking identified three compounds namely Terchebin, Locaracemoside B and 1,2,4,6 Tetra o Galloyl Beta D Glucose showing stable interactions with DPP4 similar to the standard drug Vildagliptin. The network pharmacology analysis of NK identified a number of targets like TNFα, TGFβ1, SOD1, SOD2, AKT1, DPP4 and GLP1R in its protein-protein interaction network which are vital to diabetic progression and complications. The present work demonstrated that the polyherbal formulation NK has DPP4 inhibition potential and modulates a large number of diabetes related proteins and pathways. The approach adopted in the current study by combiningin vitroandin silicomethods allowed us to understand the mechanism of DPP4 inhibition by the formulation and also the possible pharmacological networking through which the formulation exert its systemic effect in diabetes management.

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. Keywords: Lodhrasavam, Ayurveda, Formulation standardization, Sensorial attributes, Physico-chemical characters

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.

Background: Pistacia chinensis subsp. integerrima (J. L. Stewart ex Brandis) Rech. f. belongs to family Anacardiaceae, is well known for usage of galls in traditional medicine. The galls in the apical meristem of plants are induced by aphid Baizongia pistaciae L infestation. The Pistacia galls are used in Ayurvedic formulations for the treatment of cough and respiratory diseases, loss of appetite, dyspeptic vomiting and dysentery. The drastic decrease in the gall formation in recent decades is possibly due to climate change or human interventions, making it an important species from conservation point of view. There is not much work carried out at molecular level to understand the gall development. In this study, we obtained molecular insight on insect and plant through genomic, transcriptomic and proteomic approaches. Results: We sequenced the whole genome of Pistacia genome using Illumina sequencing platform. The assembly genome size of Pistacia was 549 Mb with 80688 scaffolds at N50 = 12607 nts. A total of 51290 genes were from Pistacia genome annotation. The transcriptome analysis revealed of 76186 and 46327 transcripts from gall and leaf, respectively. The ethylene responsive transcription factor families were induced abundantly in galls including GATA, bHLH, MYB, BZIP, Trihelix, MADS, B3 domain. In addition, we have also obtained highly expressed genes in gall for biosynthesis of secondary metabolites, plant-aphid interactions, stress responses, phytohormone signal transduction and terpene biosynthesis. We have identified 21 proteins against Cajanus cajan , 10 proteins against Arabidopsis thaliana and 14 proteins against Drosophila melanogaster . We also identified abundant peptides for actin and tubulin of aphid in the gall tissue. Conclusion: This study provides a basis for the understanding of the genes expressed in gall when compared to leaf and also genes required for gall induction and development. We hypothesed that actin and microtubule proteins are from aphids origin as we found that transcript TRINITY_DN180182_c0_g1_i1 mapped to Acyrthosiphon pisum tubulin beta-1 (Tub1), mRNA with 75 % homology.

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.

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.

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.

Despite the diversity, an Indian meal would invariably contain a dish made of milk products. Milk and milk products are considered as wholesome food (pathya) or rejuvenator (rasayana), which can be correlated to modern probiotics and prebiotics that increases the life force (ojas). Ayurveda explains a physiological component/process called agni, - responsible for digestion and metabolism. Fermented milk products are known to normalize agni. Ayurvedic treatises dedicate chapters to describe types of milk, preparation of various fermented milk products, and their medicinal uses, which are not known to modern world. Use of fermented milk has been indicated as treatment/diet in many gastrointestinal diseases. The word probiotics per se and the microorganisms involved have not been mentioned in the ancient texts, but Indian medicine was certainly aware about the specific uses of dairy products for health benefits and was well-documented. This calls for a closer scientific scrutiny.