alpha-Spinasterol isolated from the root of Phytolacca americana and its pharmacological property on diabetic nephropathy.
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 alpha-spinasterol (C (29)H (48)O), a delta (7)-sterol. This phytosterol proved to be a potent inhibitor (IC (50) = 3.9 x 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. alpha-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 alpha-spinasterol has a significant therapeutic potential to modulate the development and/or progression of diabetic nephropathy.
Department of Pharmacology, Wonkwang University School of Medicine, Jeonbuk, Korea.
Seung I
SI
Jeong
Kang Ju
KJ
Kim
Min Kyu
MK
Choi
Kyung Soo
KS
Keum
Seoul
S
Lee
Seon Ho
SH
Ahn
Seung Hoon
SH
Back
Ju Hung
JH
Song
Young Sung
YS
Ju
Bong Kyu
BK
Choi
Kyu Yong
KY
Jung
D000818:Animals; D002455:Cell Division; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D029604:Phytolacca americana; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D010936:Plant Extracts; D013311:Streptozocin