Antidiabetic potential of polyherbal formulation DB14201: Preclinical development, safety and efficacy studies. (2nd February 2017)

• Record Type: Journal Article
• Authors: Gopalakrishna Pillai, Geetha Krishnan; Bharate, Sonali S.; Awasthi, Anshumali; Verma, Ritu; Mishra, Gautam; Singh, Anu T.; Jaggi, Manu; Mithal, Ambrish; Vishwakarma, Ram A.
• Is Part Of: Journal of ethnopharmacology. Volume 197(2017)
• Page Start: 218
• Page End: 230
• Publication Date: 2017-02-02
• Subjects: WHO World Health Organization -- US-FDA US Food and Drug Administration -- ADME Absorption, Distribution, Metabolism, and Excretion -- HPLC High-performance liquid chromatography -- EDTA Ethylenediaminetetraacetic acid -- MS mass spectrometry -- Pb Lead -- Cd Cadmium -- Hg Mercury -- As Arsenic -- TNF-α Tumor necrosis factor alpha -- DMEM Dulbecco's Modified Eagle Medium -- FBS Fetal Bovine Serum -- IBMX Isobutylmethylxanthine -- CO2 Carbon dioxide -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide -- DMSO Dimethyl sulfoxide -- SGOT Serum glutamic oxaloacetic transaminase -- SGPT Serum glutamic-pyruvic transaminase -- ELISA Enzyme-linked immunosorbent assay -- AST Aspartate aminotransferase -- ALT Alanine aminotransferase -- LOD limit of detection -- LOQ limit of quantitation -- PBS Phosphate-buffered saline -- 2-NBDG 2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxy-D-glucose -- IL-6 Interleukin 6 -- LPS Lipopoly-saccharide -- GTT Glucose Tolerance Test -- SOD Superoxide dismutase -- OECD Organization for Economic Co-operation and Development -- ICP-MS Inductively coupled plasma mass spectrometry; Polyherbal formulation -- Diabetes -- Efficacy -- Acute toxicity -- Repeated dose toxicity -- Mechanistic studies; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2016.07.062
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: The poly-herbal formulation DB14201 is a new combination of ayurvedic ingredients for treatment of diabetes. The aim of present study was to investigate safety and in vivo efficacy of DB14201 extract. Further this work was aimed to develop, characterize and standardize DB14201 extract and develop it as a botanical drug. Materials and methods: The polyherbal extract was standardized using four chemical markers. The LC-MS/MS method was developed for identification and quantification of mangiferin, berberine, kaempferol and curcumin. The extract was standardized for heavy metal content, aflotoxins, and microbial tests. The mechanism of action of DB14201 extract was explored through glucose uptake by adipocytes, TNF-α production and free fatty acid release, in vitro, was studied using murine adipocytes (3T3-L1). The effect of extract on insulin release was evaluated using murine pancreatic beta cell (β TC-6). The safety and in vivo efficacy of extract was studied using suitable animal model. Hematology and blood biochemistry parameters were also assessed. Results: In vitro studies of DB14201 in murine adipocytes and murine pancreatic beta cells demonstrated the plausible mechanism of action of DB14201 could be through increase in glucose uptake and by stimulation of insulin release by RIN-5f cells. The microbial load, heavy metals were found to be within the AYUSH permissible limits and aflotoxins were absent. Preclinical efficacy studies in animal models proved the anti-diabetic potential of the extract. The preclinical acute dose toxicity study and 90-days repeated dose toxicity study of DB14201 extract in wistar rats by oral route indicated that the extract is safe up to 1000 mg/kg dose. Hematology and blood biochemistry parameters were within the normal range. Conclusions: The data presented herein demonstrated anti-diabetic potential of developed DB14201 extract and this study will serve as the benchmark for the further research on this polyherbal formulation. Graphical abstract: