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 (C 29 H 48 O), a Δ 7 -sterol. This phytosterol proved to be a potent inhibitor (IC 50 = 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.