Effect of Lanostane Triterpenes from the Fruiting Bodies of Ganoderma lucidum on Adipocyte Differentiation in 3T3-L1 Cells

Abstract

Two new lanostane triterpenes, methyl lucidenate N (1) and t-butyl lucidenate B (2), were isolated from the fruiting bodies of Ganoderma lucidum together with five known compounds (3–7). The structures of the two new triterpenes were established as methyl 3β,7β-dihydroxy-4,4,14α-trimethyl-11,15-dioxo-5α-chol-8-en-24-oate (1) and t-butyl 7β,12β-dihydroxy-4,4,14α-trimethyl-3,11,15-trioxo-5α-chol-8-en-24-oate (2) by extensive spectroscopic studies and chemical evidence. The effect of the isolated compounds (1–7) on triglyceride (TG) accumulation, an indicator of adipocyte differentiation, during the differentiation of 3T3-L1 preadipocytes was examined. t-Butyl lucidenate B (2) reduced the TG accumulation significantly by 72 % at 80 µM compared to the untreated group. Furthermore, compound 2 effectively suppressed the GPDH activity in the cells. Consistent with the decrease in TG accumulation and GPDH activity, compound 2 suppressed the gene expressions of PPARγ, C/EBPα, and SREBP-1c in a dose-dependent manner during differentiation. Our findings demonstrate that the lanostane triterpenes isolated in this study contribute to the inhibitory effect of the fruiting bodies of G. lucidum on adipocyte differentiation in 3T3-L1 cells.

Key words

Ganoderma lucidum - Polyporaceae - lanostane triterpenes - antiobesity - adipocyte differentiation - adipogenic transcript factor

References

• 1 Furuyashiki T, Nagayasu H, Aoki Y, Bessho H, Hashimoto T, Kanazawa K. Tea catechin suppresses adipocyte differentiation accompanied by down-regulation of PPARγ2 and C/EBPα in 3T3-L1 cells.  Biosci Biotechnol Biochem. 2004;  68 2353-2359
• 2 Han L K, Takaku T, Li J, Kimura Y, Okuda H. Anti-obesity action of oolong tea.  Int J Obes Relat Metab Disord. 1999;  23 98-105
• 3 Hsu C L, Yev G C. Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 Cells.  J Agric Food Chem. 2007;  55 1730-1736
• 4 Hsu C L, Yev G C. Effects of flavonoids and phenolic acids on the inhibition of adipogenesis in 3T3-L1 adipocytes.  J Agric Food Chem. 2007;  55 8404-8410
• 5 Liu D Z, Wang F, Liao T G, Tang J G, Steglich W, Zhu H J, Liu J K. Vibralactone: a lipase inhibitor with an unusual fused β-lactone produced by cultures of the basidiomycete Boreostereum vibrans.  Org Lett. 2006;  8 5749-5752
• 6 Min B S, Nakamura N, Miyashiro H, Bae K W, Hattori M. Triterpenes from the spores of Ganoderma lucidum and their inhibitory activity against HIV-1 protease.  Chem Pharm Bull. 1998;  46 1607-1612
• 7 Kimura S, Tamura T J. Dietary effects of Ganoderma lucidum mushroom on blood pressure and lipid levels in spontaneously hypotensive rats (SHR).  Nutr Sci Vitam. 1988;  34 433-438
• 8 Kim D H, Shim S B, Kim N J, Jang J S. Beta-glucuronidase-inhibitory activity and hepatoprotective effect of Ganoderma lucidum.  Biol Pharm Bull. 1999;  22 162-164
• 9 Toth J O, Luu B, Ourision G. Les acides ganoderiques T & Z, triterpens cytotoxiques de Ganoderma lucidum (Polyporaceae).  Tetrahedron Lett. 1983;  24 1081-1084
• 10 Tasaka K, Mio M, Isushi K, Akagi M, Mikino T. Anti-allergic constituents in the culture medium of Ganoderma lucidum (II). The inhibitory effect of cyclooctasulfur on histamine release.  Agents Actions. 1988;  23 157-160
• 11 Komoda Y, Shimizu M, Sonoda Y, Sato Y. Ganoderic acid and its derivatives as cholesterol synthesis inhibitors.  Chem Pharm Bull. 1990;  38 1359-1364
• 12 Lee C W, Yoon H M, Kang K H. Adipocyte-related genes and transcription factors were affected by Ganoderma lucidum during 3T3-L1 differentiation.  J Korean Inst Herbal Acupunct. 2009;  12 213-220
• 13 Wu T S, Shi L S, Kuo S C. Cytotoxicity of Ganoderma lucidum triterpenes.  J Nat Prod. 2001;  64 1121-1122
• 14 Nishitoba T, Sato H, Kasai T, Kawagishi H, Sakamura S. New bitter C₂₇ and C₃₀ terpenoids from the fungus Ganoderma lucidum (Reishi).  Agric Biol Chem. 1985;  49 1793-1798
• 15 Iwatsuki K, Akihisa T, Tokuda H, Ukiya M, Oshikubo M, Kimura Y, Asano T, Nomura A, Nishino H. Lucidenic acids P and Q, methyl lucidenate P, and other triterpenoids from the fungus Ganoderma lucidum and their inhibitory effects on Epstein-Barr virus activation.  J Nat Prod. 2003;  66 1582-1585
• 16 Kikuchi T, Kanomi S, Murai Y, Kadota S, Tsubono K, Ogita Z I. Constituents of the fungus Ganoderma lucidum (FR.) Karst. II. Structures of ganoderic acids F, G, and H, lucidenic acids D2 and E2, and related compounds.  Chem Pharm Bull. 1986;  34 4018-4029
• 17 Wise L S, Green H. Participation of one isozyme of cytosolic glycerophosphate dehydrogenase in the adipose conversion of 3T3 cells.  J Biol Chem. 1979;  254 273-275
• 18 Rosen E D, Walkey C J, Puigserver P, Spiegelman B M. Transcriptional regulation of adipogenesis.  Genes Dev. 2000;  14 1293-1307
• 19 Kim J B, Spiegelman B M. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism.  Genes Dev. 1996;  10 1096-1107
• 20 Soukas A, Cohen P, Socci N D, Friedman J M. Leptin-specific patterns of gene expression in white adipose tissue.  Genes Dev. 2000;  14 963-980