title: Promising Inhibitory Effects of Anthraquinones, Naphthopyrone, and Naphthalene Glycosides, from Cassia obtusifolia on α-Glucosidase and Human Protein Tyrosine Phosphatases 1B.
abstract: The present work aims to evaluate the anti-diabetic potentials of 16 anthraquinones, two naphthopyrone glycosides, and one naphthalene glycoside fromCassia obtusifoliavia inhibition against the protein tyrosine phosphatases 1B (PTP1B) and α-glucosidase. Among them, anthraquinones emodin and alaternin exhibited the highest inhibitory activities on PTP1B and α-glucosidase, respectively. Moreover, we examined the effects of alaternin and emodin on stimulation of glucose uptake by insulin-resistant human HepG2 cells. The results showed that alaternin and emodin significantly increased the insulin-provoked glucose uptake. In addition, our kinetic study revealed that alaternin competitively inhibited PTP1B, and showed mixed-type inhibition against α-glucosidase. In order to confirm enzyme inhibition, we predicted the 3D structure of PTP1B using Autodock 4.2 to simulate the binding of alaternin. The docking simulation results demonstrated that four residues of PTP1B (Gly183, Arg221, Ile219, Gly220) interact with three hydroxyl groups of alaternin and that the binding energy was negative (-6.30 kcal/mol), indicating that the four hydrogen bonds stabilize the open form of the enzyme and potentiate tight binding of the active site of PTP1B, resulting in more effective PTP1B inhibition. The results of the present study clearly demonstrate thatC. obtusifoliaand its constituents have potential anti-diabetic activity and can be used as a functional food for the treatment of diabetes and associated complications.
authors.affiliation: Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 561-756, Korea. jungha@jbnu.ac.kr.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Jung
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan 608-737, Korea. yousufbge@gmail.com.
authors.forename: Md Yousof
authors.initials: MY
authors.lastname: Ali
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan 608-737, Korea. choijs@pknu.ac.kr.
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
mesh_terms: D002366:Cassia / Q000737:chemistry*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D004642:Emodin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors / Q000494:pharmacology*; D006027:Glycosides / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D008516:Medicine, Chinese Traditional; D062105:Molecular Docking Simulation; D009281:Naphthalenes / Q000494:pharmacology*; D028321:Plant Preparations / Q000494:pharmacology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D006027:Glycosides; D007004:Hypoglycemic Agents; D009281:Naphthalenes; D028321:Plant Preparations; C053054:2-hydroxyemodin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D000520:alpha-Glucosidases; D005947:Glucose; D004642:Emodin
keywords: Cassia obtusifolia; PTP1B; alaternin; anthraquinones; insulin resistance; α-glucosidase