title: Antidiabetic property of Symplocos cochinchinensis is mediated by inhibition of alpha glucosidase and enhanced insulin sensitivity.
abstract: The study is designed to find out the biochemical basis of antidiabetic property of Symplocos cochinchinensis (SC), the main ingredient of 'Nisakathakadi' an Ayurvedic decoction for diabetes. Since diabetes is a multifactorial disease, ethanolic extract of the bark (SCE) and its fractions (hexane, dichloromethane, ethyl acetate and 90% ethanol) were evaluated by in vitro methods against multiple targets relevant to diabetes such as the alpha glucosidase inhibition, glucose uptake, adipogenic potential, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B) and dipeptidyl peptidase-IV (DPP-IV). Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition (IC50 value-82.07 ± 2.10 µg/mL), insulin dependent glucose uptake (3 fold increase) in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F (3.5 fold increase) and reduced triglyceride accumulation (22% decrease) in 3T3L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells (59.57% decrease) with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence and quantity of bioactives (beta-sitosterol, phloretin 2'glucoside, oleanolic acid) in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in in vivo diabetic models. We conclude that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with moderate antiglycation and antioxidant activity.
authors.affiliation: Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, Kerala, India.
authors.forename: Kalathookunnel Antony
authors.initials: KA
authors.lastname: Antu
authors.affiliation: Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, Kerala, India.
authors.forename: Mariam Philip
authors.initials: MP
authors.lastname: Riya
authors.affiliation: Division of Biochemistry, Council of Scientific and Industrial Research-Central Drug Research Institute (CSIR-CDRI), Lucknow, Uttar Pradesh, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Medicinal Chemistry Division, CSIR-CDRI, Lucknow, Uttar Pradesh, India.
authors.forename: Karunakaran S
authors.initials: KS
authors.lastname: Anilkumar
authors.affiliation: Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, Kerala, India.
authors.forename: Chandrasekharan K
authors.initials: CK
authors.lastname: Chandrakanth
authors.affiliation: Division of Pharmacology, CSIR-CDRI, Lucknow, Uttar Pradesh, India.
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Tamrakar
authors.affiliation: Division of Biochemistry, Council of Scientific and Industrial Research-Central Drug Research Institute (CSIR-CDRI), Lucknow, Uttar Pradesh, India.
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Srivastava
authors.affiliation: Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, Kerala, India.
authors.forename: K Gopalan
authors.initials: KG
authors.lastname: Raghu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002417:Cattle; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007333:Insulin Resistance; D019684:Magnoliopsida / Q000737:chemistry*; D008297:Male; D008515:Medicine, Ayurvedic; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013311:Streptozocin; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D012710:Serum Albumin, Bovine; D013311:Streptozocin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat; D000520:alpha-Glucosidases; D018819:Dipeptidyl Peptidase 4