Neurite Outgrowth Activity of Cyathane Diterpenes from Sarcodon cyrneus, Cyrneines A and B

Abstract

Two new cyathane diterpenes, cyrneines A (1) and B (2), were isolated from the mushroom Sarcodon cyrneus. The structures of the novel diterpenoids were determined by analysis of their spectroscopic data. Neither cyrneine A nor cyrneine B at 100 μM showed cytotoxicity as determined by LDH analysis. The stimulating activity on neurite outgrowth of cyrneines was evaluated. Rat pheochromocytoma cells (PC12), used as a model system of neuronal differentiation, were cultured with cyrneine A (100 μM), cyrneine B (100 μM) or NGF (100 ng/ml) for 24 h. Interestingly, cyrneines A and B significantly promoted neurite outgrowth in addition to NGF as a positive control.

Key words

Sarcodon cyrneus - Basidiomycetes - cyathane diterpenes - cyrneine A - cyrneine B - neurite outgrowth

References

• 1 Allbutt A D, Ayer W A, Brodie H J, Johri B N, Taube H. Cyathin, a new antibiotic complex produced by Cyathus helenae .  Can J Microbiol. 1971;  17 1401-7
• 2 Hecht H J, Höfle G, Steglich W, Anke T, Oberwinkler F. Striatin A, B, and C: novel diterpenoid antibiotics from Cyathus striatus . J Chem Soc, Chem. Commun 1978: 665-6
• 3 Kawagishi H, Shimada A, Shirai R, Okamoto K, Ojima F, Sakamoto H. et al . Erinacines A, B. and C, strong stimulators of nerve growth factor (NGF)-synthesis from the mycelia of Hercium erinaceum .  Tetrahedron Lett. 1994;  35 1569-72
• 4 Ohta T, Takako K, Norihiro K, Obara Y, Norimichi N, Yasushi O, Yoshiaki T, Yoshiteru O. Scabronine A, a novel diterpenoid having potent inductive activity of the nerve growth factor synthesis, isolated from the mushroom Sarcodon scabrosus .  Tetrahedron Lett. 1998;  39 6 229-32
• 5 Kita T, Takaya Y, Oshima Y, Ohta T, Aizawa K, Hirano T. et al . Scabronins B, C, D, E and F, novel diterpenoids showing stimulating activity of nerve growth factor-synthesis, from mushroom Sarcodon scabrosus .  Tetrahedron. 1998;  54 11 877-86
• 6 Anke T, Oberwinkler F, Steglich W, Höfle G. Antibiotics from Basidiomycetes, 1. The striatins - new antibiotics from the Basidiomycete Cyathus striatus (Huds. Ex Pers.) Willd.  J Antibiot. 1977;  30 221-5
• 7 Hirota M, Moritura K, Shibata H. Anti-inflammatory compounds from the bitter mushroom, Sarcodon scabrosus .  Biosci Biotechnol Biochem. 2002;  66 179-84
• 8 Kamo T, Imura Y, Hagio T, Makabe H, Shibata H, Hirota M. Anti-inflammatory cyathane diterpenoids from Sarcodon scabrosus .  Biosci Biotechnol Biochem. 2004;  68 1362-5
• 9 Rosas-Romero A, Martinez Manchado C, Crescente O, Acosta M, Curini M, Epifano F. et al . Anti-inflammatory sesquiterpene lactones from Lourteigia ballotaefolia .  Planta Med. 2002;  68 841-3
• 10 Curini M, Maltese F, Marcotullio M C, Menghini L, Pagiotti R, Rosati O. et al . Glaucopines A and B, new cyathane diterpenes from the fruiting bodies of Sarcodon glaucopus .  Planta Med. 2005;  71 194-6
• 11 Marcotullio M C, Pagiotti R, Campagna V, Maltese F, Fardella G, Altinier G. et al .Glaucopine C, a new diterpene from the fruiting bodies of Sarcodon glaucopus . Nat Prod Res, in press
• 12 Obara Y, Nakahata N, Kita T, Takaya Y, Kobayashi H, Hosoi S. et al . Stimulation of neurotrophic factors secretion from 1321N1 human astrocytoma cells by novel diterpenoids, scabronines A and G.  Eur J Pharmacol. 1999;  370 79-84
• 13 Obara Y, Kobayashi H, Ohta T, Ohizumi Y, Nakahata N. Scabronine G-methyl ester enhances secretion of neurotrophic factors mediated by an activation of protein kinase C-ξ.  Mol Pharmacol. 2001;  59 1287-97
• 14 Levi Montalcini R. The nerve growth factor: 35 years later.  Science. 1987;  237 1154-62
• 15 Furukawa Y, Furukawa S. Catecholamines induce an increase in nerve growth factor content in the medium of mouse L-M cells.  J Biol Chem. 1986;  261 6039-47
• 16 Veenstra T D, Fahnestock M, Kumar R. AP-1 site in the nerve growth factor expression in osteoblast.  Biochemistry. 1998;  37 5988-94
• 17 Takeuchi R, Murase K, Furukawa Y, Furukawa S, Hayashi K. Stimulation of nerve growth factor synthesis/secretion by 1,4-benzoquinone and its derivative in cultured mouse astroglial cells.  FEBS Lett. 1990;  261 63-6
• 18 Kawagishi H, Ando M, Shinba K, Sakamoto H, Yoshida S, Ojima F. et al . Chromans, hericenones F, G and H from the Mushroom Hericium erinaceum .  Phytochemistry. 1993;  32 175-8
• 19 Obara Y, Aoki T, Kusano M, Ohizumi Y. β-Eudesmol induces neurite outgrowth in rat pheochromocytoma cells accompanied by an activation of mitogen-activated protein kinase.  J Pharmacol Exp Ther. 2002;  301 803-11
• 20 Tori M, Toyoda N, Sono M. Total synthesis of allocyathin B₂, a metabolite of bird's nest fungi.  J Org Chem. 1998;  63 306-13