α-Spinasterol Isolated from the Root of Phytolacca americana and its Pharmacological Property on Diabetic Nephropathy

Abstract

Based on an inhibitory activity-guided fractionation for the high glucose-induced proliferation of glomerular mesangial cells (GMCs), chloroform extracts of the roots of Phytolacca americana were found to contain α-spinasterol (C₂₉H₄₈O), a Δ⁷-sterol. This phytosterol proved to be a potent inhibitor (IC₅₀ = 3.9 × 10^-12 g/mL, 9.5 pmol/L) of glomerular mesangial cell proliferation caused by high-ambient glucose (5.6 mM vs. 25 mM), and its inhibitory potency was about 1,000 times higher than that of simvastatin, an HMG-CoA reductase inhibitor used as a positive control. α-Spinasterol also significantly reduced the increases of serum triglycerides, renal weight and urinary protein excretion in streptozotocin-induced diabetic mice, and these were comparable to the results observed in insulin-treated diabetic mice. Therefore, the results obtained in this study suggest that α-spinasterol has a significant therapeutic potential to modulate the development and/or progression of diabetic nephropathy.

Key words

α-Spinasterol - Phytolacca americana L. - Phytolaccaceae - glomerular mesangial cells - diabetic nephropathy

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