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.

Identification of natural products with neuronal and metabolic benefits through autophagy induction

“…The preselection was based on the documented hypoglycemic and/or neurotrophic effects of the medicinal plants against type 2 diabetes and/or neurodegeneration. [14][15][16][17][18][19][20][21][22][23][24][25][26] The purity of all compounds was above 95% (Fig. S1), assessed by HPLC (high-performance liquid chromatography) with C18 columns, or HPLC with TSK columns plus the Molisch test, which meets the analytical standard (95 %) of commercial vendors.…”

One New Veratramine-Type Alkaloid From Veratrum maackii var. japonicum and Antioxidative Activities of Isolated Compounds

“…These 1D NMR data indicated that compound 1 was a veratramine-type alkaloid. 9 One bond correlations from proton ( 1 H) to carbon ( 13 C) were assigned by heteronuclear multiple-quantum correlation (HMQC) experiment (Supplemental Material S5). The steroidal moiety was determined by the HMBC correlations (Supplemental Material S6) from H-19 to C-1, C-5, C-9, and C-10, from H-4 to C-2, C-3, C-5, and C-6, from H-7 to C-6, from H-9 to C-19, from H-11 to C-8, C-9, C-12, and C-13, and from H-18 to C-12, C-13, and C-17 and the 1 H- 1 13 C NMR spectroscopic data with jervine-3-yl formate and veratramine-3-yl acetate in the literature.…”

“…The steroidal moiety was determined by the HMBC correlations (Supplemental Material S6) from H-19 to C-1, C-5, C-9, and C-10, from H-4 to C-2, C-3, C-5, and C-6, from H-7 to C-6, from H-9 to C-19, from H-11 to C-8, C-9, C-12, and C-13, and from H-18 to C-12, C-13, and C-17 and the 1 H- 1 13 C NMR spectroscopic data with jervine-3-yl formate and veratramine-3-yl acetate in the literature. 9 Furthermore, the ROESY correlations between H-21/H-23 were assigned to be same orientation. We tentatively proposed it to be in β-orientation at H-17 by spectral comparison with the literature values.…”

Potent PPARγ Ligands from Swietenia macrophylla Are Capable of Stimulating Glucose Uptake in Muscle Cells

“…Over-expression of GLUT4 in skeletal muscle promotes glucose uptake, which offsets insulin resistance in diabetic mice [29,30]. In our study, a widely used cell type for glucose assay uptake, skeletal muscle C2C12 cell line was utilized as the model system [31,32]. Our results showed that treating muscle cells with S. macrophylla compounds promoted the translocation of GLUT4 from the intracellular compartment towards the plasma membrane, and this happens as earlier as 15 min in insulin, 6OA and Sw treated cells.…”