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Background: Lymphatic filariasis (LF) is a neglected tropical disease presenting mainly as lymphoedema (elephantiasis). At present, LF is not effectively treated. Integrative medicine (IM) treatment for lymphoedema uses a combination of Indian traditional medicine, Ayurveda, alongside yoga exercises, compression therapy, antibiotics and antifungal treatments, providing a useful combination where resources are limited and different practices are in use., Objectives: To assess the effectiveness of the IM in the existing clinical practice of lower-limb lymphoedema management and to determine whether the treatment outcomes align with the World Health Organization (WHO) global goal of LF management., Methods: Institutional data from electronic medical records of all 1698 patients with LF between 2010 and 2019 were retrospectively analysed using pre- and post-treatment comparisons and the National Institute for Health and Care Excellence guidelines for clinical audit. The primary treatment outcomes evaluated were limb volume, bacterial entry points (BEEPs), episodes of cellulitis, and health-related quality of life (HRQoL). Secondary outcomes included the influence of the patient's sex, duration of illness, education and employment status on volume reduction. Multiple regression analysis, t-test, χ2-test, analysis of variance, Mann-Whitney U-test and the Kruskal-Wallis test were used to assess the association between IM and patients' treatment outcomes., Results: Limb volume reduced by 24.5% [95% confidence interval (CI) 22.47-26.61; n = 1660] following an intensive supervised care period (mean 14.84 days, n = 1660). Limb volume further reduced by 1.42% (95% CI 0.76-2.07; n = 1259) at the first follow-up visit (mean 81.45 days), and by 2.3% between the first and second follow-up visits (mean 231.32 days) (95% CI 1.26-3.34; n = 796). BEEPs were reduced upon follow-up; excoriations (78.4%) and intertrigo (26.7%) were reduced at discharge and further improvements was achieved at the follow-up visits. In total, 4% of patients exhibited new BEEPs at the first follow-up [eczema (3.9%), folliculitis (6.5%), excoriations (11.9%) and intertrigo (15.4%); 4 of 7 BEEPs were recorded]. HRQoL, measured using the disease-specific Lymphatic Filariasis Specific Quality of Life Questionnaire, showed an average score of 73.9 on admission, which increased by 17.8 at the first follow-up and 18.6 at the second follow-up. No patients developed new cellulitis episodes at the first follow-up, and only five patients (5.3%) developed new episodes of cellulitis at the second follow-up., Conclusions: IM for lower-limb lymphoedema successfully reduces limb volume and episodes of cellulitis, and also reduces BEEPs, leading to improved HRQoL. IM aligns with the LF treatment goals of the WHO and is a low-cost, predominantly self-care management protocol. IM has the potential to change care models and improve the lives of patients with lymphoedema., Competing Interests: Conflicts of interest The authors declare they have no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Echis carinatus bite is a serious threat in South-Asian countries including India, as it causes highest number of deaths and terrifying long-term tissue destruction at the bitten site. Although venom metalloproteinases and hyaluronidases are the suggested key players, studies on the effect of venom on polymorphonuclear cells, peripheral blood mononuclear cells and platelets, and their role in long-term tissue destruction are still in infancy. While, the effect of venom on collagen receptors, integrin α2β1/GP VI/DDR1 and CX3CR1 chemokine receptor present on these cells is an untouched area., Methods: Lupeol, lupeol acetate, its synthetic derivatives 2-8 were screened for inhibition of E. carinatus venom induced-hemorrhage in mouse model where compound 8 was found to be the most potent. Further, compound 8 efficiently neutralized venom induced hemorrhage, edema, dermonecrosis, myonecrosis, myotoxicity, pro-coagulant, oxidative stress, inflammatory cytokines and cleavage of collagen and CX3CR1 receptors on inflammatory cells in in vivo, in silico, ex vivo and in vitro studies., Conclusions: This study for the first time demonstrated the cleavage of collagen receptors and the receptor for angiogenesis and wound healing by the venom and its inhibition by compound 8, as these are important for firm adhesion of inflammatory cells at the damaged site to resolve inflammation and promote tissue repair., General Significance: This study provides a lead in venom pharmacology, wherein, compound 8 could be a therapeutic agent for the better management of viper venom-induced long-term tissue destruction., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Introduction: The journals that publish on Ayurveda are increasingly indexed by popular medical databases in recent years. However, many Eastern journals are not indexed biomedical journal databases such as PubMed. Literature searches for Ayurveda continue to be challenging due to the nonavailability of active, unbiased dedicated databases for Ayurvedic literature. In 2010, authors identified 46 databases that can be used for systematic search of Ayurvedic papers and theses. This update reviewed our previous recommendation and identified current and relevant databases., Aims: To update on Ayurveda literature search and strategy to retrieve maximum publications., Methods: Author used psoriasis as an example to search previously listed databases and identify new. The population, intervention, control, and outcome table included keywords related to psoriasis and Ayurvedic terminologies for skin diseases. Current citation update status, search results, and search options of previous databases were assessed. Eight search strategies were developed. Hundred and five journals, both biomedical and Ayurveda, which publish on Ayurveda, were identified. Variability in databases was explored to identify bias in journal citation., Results: Five among 46 databases are now relevant - AYUSH research portal, Annotated Bibliography of Indian Medicine, Digital Helpline for Ayurveda Research Articles (DHARA), PubMed, and Directory of Open Access Journals. Search options in these databases are not uniform, and only PubMed allows complex search strategy. "The Researches in Ayurveda" and "Ayurvedic Research Database" (ARD) are important grey resources for hand searching. About 44/105 (41.5%) journals publishing Ayurvedic studies are not indexed in any database. Only 11/105 (10.4%) exclusive Ayurveda journals are indexed in PubMed., Conclusion: AYUSH research portal and DHARA are two major portals after 2010. It is mandatory to search PubMed and four other databases because all five carry citations from different groups of journals. The hand searching is important to identify Ayurveda publications that are not indexed elsewhere. Availability information of citations in Ayurveda libraries from National Union Catalogue of Scientific Serials in India if regularly updated will improve the efficacy of hand searching. A grey database (ARD) contains unpublished PG/Ph.D. theses. The AYUSH portal, DHARA (funded by Ministry of AYUSH), and ARD should be merged to form single larger database to limit Ayurveda literature searches.

Context: Research methodology in traditional Indian system of medicine., Aim: To determine the knowledge level of investigators conducting clinical trials in traditional medicines (TMs) including Ayurveda., Materials and Methods: This was a questionnaire survey conducted for selected researchers trained in any specialty and working in TM. 2087 researchers were selected based on selection criteria. A validated and pretested questionnaire containing the questions regarding regulatory issues, literature search, evidence-based medicine, clinical trial design, patient selection, and study reporting were sent either through E-mail or post. The answered questionnaires were analyzed. The parameters were analyzed based on median and interquartile range (IQR)., Results: Forty two responses were received through E-mail and 21 researchers responded through post. Out of 63, six researchers sent incomplete responses. Among the remaining 57 respondents; 34 (59.6%) investigators had postdoctoral degree, 43 investigators (75.4%) did not receive any structured training on research methodology, 23 (40.4%) had two decades of research experience. Thirty three (74%) of investigators who received government funding didn't have any training on research methodology. Ayurveda experts group had better knowledge compared to pharmaceutical sciences and basic science group although they had a dilemma about conducting clinical evaluation of TM within the specific framework of rigorous clinical pharmacological principles without ignoring the Ayurvedic concepts such as Dosha, Prakruti etc., Investigators below 30 years possessed higher knowledge of research methodology when analyzed based on the age. The respondents working in research organizations, government organizations, and academic institutions had lower knowledge compared to those who were in private organizations/practice., Conclusions: It is recommend that investigators, peer reviewers, and fund managers involved in traditional medicine research need training especially in research methodology.

Background: Currently there is no global program to manage lymphoedema as a result of lymphatic filariasis (LF). The primary aim of this study was to determine the efficacy of a previously proposed integrative treatment protocol, using locally available resources to address the morbidity, in a community village setting., Methods: Two LF endemic districts of south India, Gulbarga in Karnataka (GK) and Alleppey in Kerala (AK), were selected for the study. All known patients were invited to an LF camp. Patients with grade two late or three lymphoedema were enrolled. All patients were given training in the integrative procedure which involved patient education and the domiciliary protocol., Results: A total of 730 patients (851 limbs) completed the three and half month follow up. There was a statistically significant (1%) reduction up to mid thigh level volume measurement for both small (0.7-1.1 liters) and large (1.8-5.0 liters) limbs, p < 0.000. In AK inflammatory episodes at the three months interval reduced from 37.5% (127 patients) to 28.3% (96 patients) and in GK from 37.6% (147 patients) to 10.2% (40 patients), p < 0.000. All patients had reduced bacterial entry points. There was an overall improvement in quality of life in all domains of LF specific quality of life questionnaire p < 0.000., Conclusions: Self care and integrative treatment is possible in resource poor Indian village settings. Further work is needed to explore factors leading to better compliance by randomizing the interventions such as washing and emollient compression vs Ayurvedic and yoga interventions before integrative treatment is considered for national health programmes in developing countries.

The diastereomeric mixture of calophyllic acid and isocalophyllic acid (F015) isolated from the leaves of Calophyllum inophyllum was investigated for the metabolic effect on glucose transport in skeletal muscle cells. In L6 myotubes, F015 dose-dependently stimulated glucose uptake by increasing translocation of glucose transporter4 (GLUT4) to plasma membrane without affecting their gene expression. The effects on glucose uptake were additive to insulin. Inhibitors analyses revealed that F015-induced glucose uptake was dependent on the activation of phosphatidylinositol-3-kinase (PI-3-K) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), while independent to the activation of 5'AMP-activated kinase (AMPK). F015 significantly increased the phosphorylation of AKT, AS160 and ERK1/2, account for the augmented glucose transport capacity in L6 myotubes. Furthermore, F015 improved glucose tolerance and enhanced insulin sensitivity in skeletal muscle of dexamethasone-induced insulin resistant mice. Our findings demonstrate that F015 activates glucose uptake in skeletal muscle cells through PI-3-K- and EKR1/2-dependent mechanisms and can be a potential lead for the management of diabetes and obesity., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. α-Glucosidase (EC 3.2.1.20) inhibitors interfere with enzymatic action to slow down the liberation of d-glucose from oligosaccharides and disaccharides, resulting in delayed glucose absorption and decreased postprandial plasma glucose levels. In continuation of our drug discovery program on antidiabetic agents, we synthesized novel N-allylated/N-alkylated niacin and α-amyrin (4-9) and lupeol (12-16) hybrids and tested for their α-glucosidase inhibiting activity. Compounds 4-9 showed better activity profile than the marketed α-glucosidase inhibitor i.e. acarbose. Compound 4 possess the highest inhibitory action with IC50 of 5 μM. Kinetic and CD studies revealed that 4 inhibited the α-glucosidase in a noncompetitive manner and caused conformational changes in secondary structure of the enzyme protein., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

In continuation of our drug discovery program on Indian medicinal plants, the gastro protective mechanism of chebulinic acid isolated from Terminalia chebula fruit was investigated. Chebulinic acid was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of chebulinic acid was observed against CRU (62.9%), AS (55.3%), AL (80.67%) and PL (66.63%) induced ulcer models. The reference drug omeprazole (10 mg/kg, p.o.) showed 77.73% protection against CRU, 58.30% against AS and 70.80% against PL model. Sucralfate, another reference drug (500 mg/kg, p.o.) showed 65.67% protection in AL induced ulcer model. Chebulinic acid significantly reduced free acidity (48.82%), total acidity (38.29%) and upregulated mucin secretion by 59.75% respectively. Further, chebulinic acid significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 65.01 μg/ml as compared to the IC50 value of omeprazole (30.24 μg/ml) confirming its anti-secretory activity., (Copyright © 2013. Published by Elsevier GmbH.)