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: ChuHyun Kang, Joo-Hui Han, Joonseok Oh, Roshan Kulkarni, Wei Zhou, Daneel Ferreira, Tae Su Jang, Chang-Seon Myung, MinKyun Na
• Journal: Journal of natural products (J Nat Prod) Vol. 78 Issue 4 Pg. 803-10 (Apr 24 2015) ISSN: 1520-6025 [Electronic] United States
• PMID: 25835537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Steroids
• Thiazolidinediones
• Rosiglitazone
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Glucose

Topics

• Alkaloids (chemistry, isolation & purification, pharmacology)
• Diabetes Mellitus, Type 2 (drug therapy)
• Glucose (metabolism)
• Molecular Structure
• Muscle, Skeletal (metabolism)
• Plant Roots (chemistry)
• Plants, Medicinal (chemistry)
• Protein Tyrosine Phosphatase, Non-Receptor Type 1 (antagonists & inhibitors)
• Republic of Korea
• Rhizome (chemistry)
• Rosiglitazone
• Stereoisomerism
• Steroids (chemistry, isolation & purification, pharmacology)
• Thiazolidinediones (pharmacology)
• Veratrum (chemistry)