title: Antidiabetic potential of polyherbal formulation DB14201: Preclinical development, safety and efficacy studies.
abstract: BACKGROUND
  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.
  
  
  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 1000mg/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.
authors.affiliation: Innoveda Biological Solutions Private Limited, New Delhi, India; Department of Integrative Medicine, Medanta-The Medicity, Gurgaon, Haryana 122001, India. Electronic address: drgk2000@gmail.com.
authors.forename: Geetha Krishnan
authors.initials: GK
authors.lastname: Gopalakrishna Pillai
authors.affiliation: CSIR - Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Sonali S
authors.initials: SS
authors.lastname: Bharate
authors.affiliation: Dabur Research Foundation, Ghaziabad 201010, Uttar Pradesh, India.
authors.forename: Anshumali
authors.initials: A
authors.lastname: Awasthi
authors.affiliation: Dabur Research Foundation, Ghaziabad 201010, Uttar Pradesh, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Verma
authors.affiliation: Dabur Research Foundation, Ghaziabad 201010, Uttar Pradesh, India.
authors.forename: Gautam
authors.initials: G
authors.lastname: Mishra
authors.affiliation: Dabur Research Foundation, Ghaziabad 201010, Uttar Pradesh, India.
authors.forename: Anu T
authors.initials: AT
authors.lastname: Singh
authors.affiliation: Dabur Research Foundation, Ghaziabad 201010, Uttar Pradesh, India.
authors.forename: Manu
authors.initials: M
authors.lastname: Jaggi
authors.affiliation: Division of Endocrinology and Diabetes, Medanta-The Medicity, Gurgaon, Haryana 122001, India.
authors.forename: Ambrish
authors.initials: A
authors.lastname: Mithal
authors.affiliation: CSIR - Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Ram A
authors.initials: RA
authors.lastname: Vishwakarma
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001599:Berberine / Q000009:adverse effects / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D002853:Chromatography, Liquid / Q000379:methods; D003474:Curcumin / Q000009:adverse effects / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D044949:Kaempferols / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D019216:Metals, Heavy / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000009:adverse effects* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D044004:Xanthones / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D044949:Kaempferols; D019216:Metals, Heavy; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; D001599:Berberine; C013592:mangiferin; C006552:kaempferol; D003474:Curcumin; D005947:Glucose
keywords: Acute toxicity; Diabetes; Efficacy; Mechanistic studies; Polyherbal formulation; Repeated dose toxicity