title: Discovering Bisdemethoxycurcumin from Curcuma longa rhizome as a potent small molecule inhibitor of human pancreatic α-amylase, a target for type-2 diabetes.
abstract: Curcuma longa rhizome is used extensively in culinary preparations in Far East and South-East Asia. Health benefits of curcuminoids from C. longa as antioxidants, anti-cancer and anti-inflammatory molecules have been well documented. We report here for the first time that Bisdemethoxycurcumin (BDMC) from C. longa, acts as an inhibitor to inactivate human pancreatic α-amylase, a therapeutic target for oral hypoglycemic agents in type-2 diabetes. Bioactivity guided isolation of rhizome isopropanol extract led to the identification by HPLC and NMR of BDMC as a lead small molecule inhibitor of porcine and human pancreatic α-amylase with an IC(50) value of 0.026 and 0.025 mM, respectively. Kinetic analysis revealed that using starch as the substrate, HPA exhibited an uncompetitive mode of inhibition with an apparent K(i) of 3.0 μM. The study gains importance as BDMC could be a good drug candidate in development of new inhibitors of HPA and of functional foods for controlling starch digestion in order to reduce post-prandial hyperglycemia.
authors.affiliation: Institute of Bioinformatics and Biotechnology, University of Pune, Pune 411 007, Maharashtra, India.
authors.forename: Sudha
authors.initials: S
authors.lastname: Ponnusamy
authors.forename: Smita
authors.initials: S
authors.lastname: Zinjarde
authors.forename: Shobha
authors.initials: S
authors.lastname: Bhargava
authors.forename: P R
authors.initials: PR
authors.lastname: Rajamohanan
authors.forename: Ameeta
authors.initials: A
authors.lastname: Ravikumar
mesh_terms: D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology*; D036381:Diarylheptanoids; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D055292:Pancreatic alpha-Amylases / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification; D027343:Rhizome / Q000737:chemistry*
chemical_list: D036381:Diarylheptanoids; D004791:Enzyme Inhibitors; D010936:Plant Extracts; C034786:bisdemethoxycurcumin; D055292:Pancreatic alpha-Amylases; D003474:Curcumin