title: Steroidal Alkaloids from Veratrum nigrum Enhance Glucose Uptake in Skeletal Muscle Cells.
abstract: Veratrum nigrum is recognized as a medicinal plant used for the treatment of hypertension, stroke, and excessive phlegm. Chemical investigation of the roots and rhizomes led to the isolation of five new steroidal alkaloids, jervine-3-yl formate (1), veramarine-3-yl formate (2), jerv-5,11-diene-3β,13β-diol (3), (1β,3β,5β)-1,3-dihydroxyjervanin-12(13)-en-11-one (4), and veratramine-3-yl acetate (5). Compounds 1 and 5 exhibited potent inhibitory activity (11.3 and 4.7 μM, respectively) against protein tyrosine phosphatase 1B (PTP1B), which has emerged as a viable target for treatment of type 2 diabetes mellitus. On the basis of their PTP1B inhibitory activity, the compounds were evaluated for their potential to enhance glucose uptake in C2C12 skeletal muscle cells. The insulin-stimulated glucose uptake was enhanced upon treatment with compounds 1 and 5 (10 μM) by 49.9 ± 6.5% and 56.0 ± 9.7%, respectively, in a more potent manner than that with the positive control rosiglitazone (47.3 ± 3.4% at 30 μM). These results suggest that steroidal alkaloids serve as practical antidiabetes mellitus leads capable of enhancing glucose uptake.
authors.affiliation: †College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: ChuHyun
authors.initials: C
authors.lastname: Kang
authors.affiliation: †College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Joo-Hui
authors.initials: JH
authors.lastname: Han
authors.affiliation: ‡Division of Pharmacognosy, Department of BioMolecular Sciences and Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Joonseok
authors.initials: J
authors.lastname: Oh
authors.affiliation: †College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Roshan
authors.initials: R
authors.lastname: Kulkarni
authors.affiliation: †College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: ‡Division of Pharmacognosy, Department of BioMolecular Sciences and Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Daneel
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: §Institute of Green Bio Science and Technology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Tae Su
authors.initials: TS
authors.lastname: Jang
authors.affiliation: †College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Chang-Seon
authors.initials: CS
authors.lastname: Myung
authors.affiliation: †College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: MinKyun
authors.initials: M
authors.lastname: Na
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005947:Glucose / Q000378:metabolism*; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors; D056910:Republic of Korea; D027343:Rhizome / Q000737:chemistry; D000077154:Rosiglitazone; D013237:Stereoisomerism; D013256:Steroids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology; D014703:Veratrum / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D013256:Steroids; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D005947:Glucose