Isolation and Bioactivity Evaluation of Terpenoids from the Medicinal Fungus Ganoderma sinense

Abstract

A new pentanorlanostane, ganosineniol A (1), eight new lanostane triterpenoids, ganosinoside A (2), ganoderic acid Jc (3), ganoderic acid Jd (4), ganodermatetraol (5), ganolucidic acid γa (6), ganolucidate F (7), ganoderiol J (8), and methyl lucidenate Ha (9), and a new sesquiterpenoid, ganosinensine (10), together with eleven known triterpenoids (11–21), were isolated from the fruiting bodies of the fungus Ganoderma sinense. Chemical structures were determined based on spectroscopic evidence, including 1D, 2D NMR, and mass spectral data. Furthermore, all isolates were tested for cytotoxic activity and induction ability of hPXR-mediated CYP3A4 expression. Among them, ganoderic acid Jc (3) displayed selective inhibitory activity against HL-60 cells (IC₅₀ = 8.30 µM), and ganoderiol E (11) exhibited selective cytotoxic activity against MCF-7 cells (IC₅₀ = 6.35 µM). Meanwhile, compounds 5, 7, and ganolucidic acids B and C (19, 20) showed induction ability of hPXR-mediated CYP3A4 expression.

Ganoderma sinense - Ganodermataceae - triterpenoids - sesquiterpene - cytotoxicity - CYP3A4 induction

References

• 1 Lu W L, Lin Z P, Lin Z B. Lucid ganoderma . Chapter 5. Beijing: Science Press; 1985: 108-122
• 2 Chen R Y, Yu D Q. Progress of studies on the chemical constituents of Ganoderma triterpene.  Acta Pharm Sin. 1990;  25 940-953
• 3 Lee I S, Kim H J, Youn U J, Kim J P, Min B S, Jung H J, Na M K, Hattori M, Bae K H. Effect of lanostane triterpenes from the fruiting bodies of Ganoderma lucidum on adipocyte differentiation in 3T3-L1 cells.  Planta Med. 2010;  76 1558-1563
• 4 Dine R S E, Halawany A M E, Ma C M. Anti-HIV-1 protease activity of lanostane triterpens from the Vietnamese mushroom Ganoderma colossum.  J Nat Prod. 2008;  71 1022-1026
• 5 Niedermeyer T H J, Lindequist U, Mentel R, Gördes D, Schmidt E, Thurow K, Lalk M. Antiviral terpenoid constituents of Ganoderma pfeifferi.  J Nat Prod. 2005;  68 1728-1731
• 6 Gao J J, Min B S, Ahn E M, Nakamura N, Lee H K, Hattori M. New triterpene aldehides luciadehides A–C from ganoderma and their cytotoxicity against murine and human tumor cells.  Chem Pharm Bull. 2002;  50 837-840
• 7 Fatmawati S, Shimizu K, Kondo R. Inhibition of aldose reductase in vitro by constituents of Ganoderma lucidum.  Planta Med. 2010;  76 1691-1693
• 8 Ko H H, Hung D F, Wang J P, Lin C N. Antiinflammatory triterpenoids and steroids from Ganoderma lucidum and G. tsugae.  Phytochemistry. 2008;  69 234-239
• 9 Qiao Y, Zhang X M, Qiu M H. Two novel lanostane triterpenoids from Ganoderma sinense.  Molecules. 2007;  12 2038-2046
• 10 Sato N, Ma C M, Komatsu K, Hattori M. Triterpene-farnesyl hydroquinone conjugates from Ganoderma sinense.  J Nat Prod. 2009;  72 958-961
• 11 Liu C, Chen R Y. A new triterpene from fungal fruiting bodies of Ganoderma sinense.  Zhongcaoyao. 2010;  41 8-11
• 12 Liu C, Zhao F, Chen R Y. A novel alkaloid from the fruiting bodies of Ganoderma sinense.  Chin Chem Lett. 2010;  21 197-199
• 13 Wang C F, Liu J Q, Yan Y X, Chen J C, Lu Y, Guo Y H, Qiu M H. Three new triterpenoids containing four-membered ring from the fruiting body of Ganoderma sinense.  Org Lett. 2010;  12 1656-1659
• 14 Mu Y, Zhang J N, Zhang S M, Zhou H H, Toma D, Ren S R, Huang L, Yaramus M, Raum A, Venkataramanan R, Xie W. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats.  J Pharmacol Exp Ther. 2006;  316 1369-1377
• 15 Hu D L, Wang G, Li Z, Fan L, Tan Z R, Wang D, Zhou H H. Establishment of in vitro screening system for CYP3A4 and CYP2B6 inducers.  China Med Eng. 2007;  15 646-649
• 16 Mosmann T. Growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
• 17 Reed L J, Muench H. A simple method of estimating fifty percent endpoints.  Am J Hyg. 1938;  27 493-497
• 18 Kohda H, Tokumoto W, Sakamoto K, Fujii M, Hirai Y, Yamasaki K, Komoda Y, Nakamura H, Ishihara S, Uchida M. The biologically active constituents of Ganoderma lucidum (Fr.) Karst. histamine release-inhibitory triterpenes.  Chem Pharm Bull. 1985;  33 1367-1374
• 19 Lin L J, Shiao M S, Yeh S F. Seven new triterpenes from Ganoderma lucidum.  J Nat Prod. 1988;  51 918-924
• 20 Gan K H, Fann Y F, Hsu S H, Kuo K W, Lin C N. Mediation of the cytotoxicity of lanostanoids and steroids of Ganoderma tsugae through apoptosis and cell cycle.  J Nat Prod. 1998;  61 485-487
• 21 Arisawa M, Fujita A, Saga M, Jukumura H, Hayashi T, Shimizu M, Morita N. Three new lanostanoids from Ganoderma lucidum.  J Nat Prod. 1986;  49 621-625
• 22 Min B S, Gao J J, Nakamura N, Hattori M. Triterpenes from the spores of Ganoderma lucidum and their cytotoxicity against Meth-A and LLC tumor cells.  Chem Pharm Bull. 2000;  48 1026-1033
• 23 Nishitoba T, Oda K, Sato H, Sakamura S. Novel triterpenoids from the fungus Ganoderma lucidum.  Agric Biol Chem. 1988;  52 367-372
• 24 Nishitoba T, Sato H, Sakamura S. Triterpenoids from the fungus Ganoderma lucidum.  Phytochemistry. 1987;  26 1777-1784
• 25 Rosslein L, Tamm C, Zürcher W. Sambucinic acid, a new metabolite of Fusarium sambucinum.  Helv Chim Acta. 1988;  71 588-595
• 26 Fujita A, Arisawa M, Saga M, Hayashi T, Morita N. Two new lanostanoids from Ganoderma lucidum.  J Nat Prod. 1986;  49 1122-1125
• 27 Sato H, Nishitoba T, Shirasu S, Oda K, Sakamura S. Ganoderiol A and B, new triterpenoids from the fungus Ganoderma lucidum (Reishi).  Agric Biol Chem. 1986;  50 2887-2890
• 28 Kikuchi T, Matsuda S, Kadota S, Murai Y, Ogita Z. Ganoderic acid-D, acid-E, acid-F and acid-H and lucidenic acid-D, acid-E, acid-F, new triterpenoids from Ganoderma lucidum.  Chem Pharm Bull. 1985;  33 2624-2627
• 29 Kikuchi T, Kanomi S, Murai Y, Kadota S, Tsubono K, Ogita Z. Constituents of the fungus Ganoderma lucidum (Fr.) Karst. III. Structure of ganolucidic acids A and B, new lanostane-type triterpenoids.  Chem Pharm Bull. 1986;  34 4030-4036
• 30 Nishitoba T, Sato H, Sakamura S. New terpenoids, ganoderic acid J and ganolucidic acid C, from the fungus Ganoderma lucidum.  Agric Biol Chem. 1985;  49 3637-3638
• 31 Gonzalez A G, Leon F, Rivera A, Munoz C M, Bermejo J. Lanostanoid triterpenes from Ganoderma lucidum.  J Nat Prod. 1999;  62 1700-1701
• 32 Frederick G J. 23,24,25,26,27-Pentanorlanost-8-en-3β,22-diol from Verticillium lecanii.  Phytochemistry. 1984;  23 1721-1723
• 33 Lin J H, Lu A Y. Inhibition and induction of cytochrome P450 and the clinical implications.  Clin Pharmacokinet. 1998;  35 361-390