title: Protein tyrosine phosphatase 1B and α-glucosidase inhibitory activities of Pueraria lobata root and its constituents.
abstract: BACKGROUND
  Pueraria lobata root was used to treat wasting-thirst regarded as diabetes mellitus and was included in the composition of Okcheonsan, which is prescribed for thirst-waste in traditional Chinese medicine.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the anti-diabetic potential of the root of Pueraria lobata and its constituents via protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities.
  
  
  METHODS
  In this study, anti-diabetic activities of the 70% ethanolic (EtOH) extract from P. lobata roots and its solvent soluble fractions with the isolated compounds were investigated by evaluating in vitro PTP1B and α-glucosidase inhibitory activities. We also examined the potentials of active compounds as PTP1B and α-glucosidase inhibitors via enzyme kinetics and in silico molecular docking simulation between the enzymes and active compounds.
  
  
  RESULTS
  Triterpenoids lupeol and lupenone were potent PTP1B inhibitors with IC50values of 38.89±0.17 and 15.11±1.23μM. Kinetic study using the Lineweaver-Burk and Dixon plots demonstrated that these compounds showed a noncompetitive-type inhibition against PTP1B with respective Kivalues of 13.88μM and 21.24μM. In addition, molecular docking simulation showed lupeol and lupenone has negative binding energy values of -8.03 and -8.56kcal/mol. Considering the α-glucosidase inhibitory potential, daidzein, genistein, and calycosin exhibited the most potent α-glucosidase inhibition with IC50values of 8.58±0.94, 2.37±0.52 and 6.84±1.58μM, respectively. Kinetic study demonstrated that these 3 compounds showed a noncompetitive-type inhibition against α-glucosidase with respective Kivalues of 17.64μM, 5.03μM and 13.83μM. Moreover, molecular docking simulation showed daidzein, genistein and calycosin has more lower binding energy (-7.16kcal/mol, -7.42kcal/mol and -7.31kcal/mol) with higher binding affinity and tight binding capacity in the molecular docking studies than standard ligand α-D-glucose (-6.74kcal/mol).
  
  
  CONCLUSIONS
  Our results of the present study clearly demonstrate the potential of P. lobata extract and its constituents to inhibit PTP1B and α-glucosidase, contributing to the development of therapeutic or preventive agents that can be used in the treatment of diabetes.
authors: Department of Food and Life Science, Pukyong National University, Busan 608-737, Republic of Korea.
authors: Su Hui
authors: SH
authors: Seong
authors: Department of Food and Life Science, Pukyong National University, Busan 608-737, Republic of Korea.
authors: Anupom
authors: A
authors: Roy
authors: Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 561-756, Republic of Korea. Electronic address: jungha@jbnu.ac.kr.
authors: Hyun Ah
authors: HA
authors: Jung
authors: Department of Food and Life Science, Pukyong National University, Busan 608-737, Republic of Korea.
authors: Hee Jin
authors: HJ
authors: Jung
authors: Department of Food and Life Science, Pukyong National University, Busan 608-737, Republic of Korea. Electronic address: choijs@pknu.ac.kr.
authors: Jae Sue
authors: JS
authors: Choi
mesh_terms: D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002852:Chromatography, Ion Exchange; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066244:Proton Magnetic Resonance Spectroscopy; D029908:Pueraria / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D010936:Plant Extracts; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Lupenone; Lupeol; Molecular docking; Protein tyrosine phosphatase 1B; Pueraria lobata; α-Glucosidase