Planta Med 2004; 70(8): 736-739
DOI: 10.1055/s-2004-827204
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

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

Seung Il Jeong1 , Kang Ju Kim2 , Min Kyu Choi3 , Kyung Soo Keum4 , Seoul Lee1 , Seon Ho Ahn5 , Seung Hoon Back5 , Ju Hung Song5 , Young Sung Ju6 , Bong Kyu Choi1 , Kyu Yong Jung1
  • 1Department of Pharmacology, Wonkwang University School of Medicine, Jeonbuk, Korea
  • 2Department of Oral Microbiology, College of Dentistry, Wonkwang University, Jeonbuk, Korea
  • 3Department of Anatomy, Wonkwang University School of Medicine, Jeonbuk, Korea
  • 4Department of Oriental Medical Informatics, Professional Graduate School of Oriental Medicine, Wonkwang University, Jeonbuk, Korea
  • 5Division of Nephrology, Department of Internal Medicine, Wonkwang University School of Medicine, Jeonbuk, Korea
  • 6Department of Herbology, College of Oriental Medicine, Woosuk University, Jeonbuk, Korea
Further Information

Publication History

Received: December 17, 2003

Accepted: May 8, 2004

Publication Date:
24 August 2004 (online)

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.

References

  • 1 Takahashi H, Namikawa Y, Tanaka M, Fukuyama Y. Triterpene glycosides from the cultures of Phytolacca americana .  Chem Pharm Bull. 2001;  49 246-8
  • 2 Kang S S, Woo W S. Two new saponins from Phytolacca americana .  Planta Medica. 1987;  10 338-40
  • 3 Mauer S M, Steffes M W, Ellis E M, Surtherland D M, Brown D M, Greth F C. Structural-functional relationships in diabetic nephropathy.  J Clin Invest. 1984;  74 1143-55
  • 4 Steffes M W, Osterby R, Cha S M. Mesangial expansion as a central mechanism for loss of kidney function in diabetic patients.  Diabetes. 1989;  38 1077-81
  • 5 Jeong S I, Kim K J, Choo Y K, Keum K S, Choi B K, Jung K Y. Phytolacca americana inhibits the high glucose-induced mesangial proliferation via suppressing extracellular matrix accumulation and TGF-β production.  Phytomedicine. 2004;  11 175-81
  • 6 Mata R, Rojas A, Acevedo L, Estrada S, Calzada F, Rojas I. et al . Smooth muscle relaxing flavonoids and terpenoids from Conyza filaginoides .  Planta Medica. 1997;  63 31-5
  • 7 Kojima H, Ogura H. Triterpenoids from Prunella vulgaris .  Phytochemistry. 1986;  25 729-33
  • 8 Itoh T, Yoshida K, Tamura T, Matsumoto T. Co-occurrence of C-24 epimeric 24-ethyl-Δ7-sterols in the roots of Trichosanthes japonica .  Phytochemistry. 1982;  21 727-30
  • 9 Danesh F R, Sadeghi M M, Amro N, Philips C, Zeng L, Lin S. et al . 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors prevent high glucose-induced proliferation of mesangial cells via modulation of Rho GTPase/p21 signaling pathway: implications for diabetic nephropathy.  Proc Natl Acad Sci USA. 2002;  99 8301-5
  • 10 Kwak D H, Rho Y I, Kwon O D, Ahn S H, Song J H, Choo Y K. et al . Decreases of ganglioside GM3 in streptozotocin-induced diabetic glomeruli of rats.  Life Sci. 2003;  72 1997-2006
  • 11 Akihisa T, Shimizu N, Ghosh P, Thakur S, Rosenstein F, Tamura T. et al . Sterols of the Cucurbitaceae.  Phytochemistry. 1987;  26 1693-700
  • 12 Willasenor I M, Lemon P, Palileo A, Bremner J B. Antigenotoxic spinasterol from Cucurbita maxima flowers.  Mutat Res. 1996;  10 89-93
  • 13 Frotan M H, Acharya S B, Frotan R, Pathak N KR, Biswas M. Pharmacological investigations on α-spinasterol isolated from Simplocos spicata .  Ind J Pharmac. 1983;  15 197-201
  • 14 Remuzzi G, Bertani T. Mechanisms of disease: pathophysiology of progressive nephropathies.  N Engl J Med. 1998;  339 1-18
  • 15 Nahman N S, Leonhart Jr K L, Cosio F G, Hebert C L. Effects of high glucose on cell proliferation and fibronectin production by cultured human mesangial cells.  Kidney Int. 1992;  41 396-402
  • 16 Wheeler D C, Chana R S. Interactions between lipoproteins, glomerular cells and matrix.  Miner Electrolyte Metab. 1993;  19 149-64
  • 17 Westrate J A, Meijer G W. Plant sterol-enriched margarines and reduction of plasma total and LDL-cholesterol in normocholesterolemic and mildly hypercholesterolemic subjects.  Eur J Clin Nutr. 1998;  52 334-43
  • 18 Krolewski A S, Laffel L M, Krolewski M, Quinn M, Warram J H. Glycosylated hemoglobin and the risk of microalbuminuria in patients with insulin-dependent diabetes mellitus.  N Engl J Med. 1995;  332 1251-5
  • 19 Rodby R A, Rohde R D, Sharon Z, Pohl M A, Bain R P, Lewis E J. The urine protein to creatinine ratio as a predictor of 24-hour urine protein excretion in type 1 diabetic patients with nephropathy.  Am J Kidney Dis. 1995;  26 904-9

Kyu Yong Jung DVM, PhD.

Department of Pharmacology

Wonkwang University School of Medicine

344-2 Shinyong-dong

Iksan

Jeonbuk 570-749

Korea

Phone: +82-63-850-6796

Fax: +82-63-851-0879

Email: wkuniv@wonkwang.ac.kr

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