Methyl ganoderate A

Lanostane triterpenoids from Ganoderma lucidum and their inhibitory effects against FAAH.[Pubmed:35961409]

Phytochemistry. 2022 Nov;203:113339.

Ganoderma lucidum is a famous edible and medicinal fungus. Through a bioactive phytochemical investigation of the ethanolic extracts of the fruiting bodies of G. lucidum, twenty-nine triterpenoids, including eleven previously undescribed triterpenoids, were isolated and characterized based on spectroscopic data. The inhibitory effects of all the triterpenes against fatty acid amide hydrolase (FAAH) were found to be in the range of 30-60% at 100 muM. Methyl ganoderate A displayed the strongest inhibitory activity (61%) against FAAH. Furthermore, all compounds displayed no cytotoxicity against LOVO and MCF-7 human cancer cells. Hence, our present study provides information about G. lucidum as a functional food or pharmaceutical supplement for the treatment of neuroinflammation.

Selective cholinesterase inhibition by lanostane triterpenes from fruiting bodies of Ganoderma lucidum.[Pubmed:21924611]

Bioorg Med Chem Lett. 2011 Nov 1;21(21):6603-7.

Two new lanostane triterpenes, named Methyl ganoderate A acetonide (1) and n-butyl ganoderate H (2), were isolated from the fruiting bodies of Ganoderma lucidum together with 16 known compounds (3-18). Extensive spectroscopic and chemical studies established the structures of these compounds as methyl 7beta,15alpha-isopropylidenedioxy-3,11,23-trioxo-5alpha-lanost-8-en-26-oate (1) and n-butyl 12beta-acetoxy-3beta-hydroxy-7,11,15,23-tetraoxo-5alpha-lanost-8-en-26-oate (2). Because new compounds exhibiting specific anti-acetylcholinesterase activity are being sought as possible drug candidates for the treatment of Alzheimer's and related neurodegenerative diseases, compounds 1-18 were examined for their inhibitory activities against acetylcholinesterase and butyrylcholinesterase. All of the compounds exhibited moderate acetylcholinesterase-inhibitory activity, with IC(50) values ranging from 9.40 to 31.03muM. In contrast, none of the compounds except lucidadiol (13) and lucidenic acid N (14) exhibited butyrylcholinesterase-inhibitory activity at concentrations up to 200muM. These results indicate that these lanostane triterpenes are preferential inhibitors of acetylcholinesterase and may be suitable drug candidates.

Steroids and triterpenes from the fruit bodies of Ganoderma lucidum and their anti-complement activity.[Pubmed:20091270]

Arch Pharm Res. 2009 Nov;32(11):1573-9.

To determine the anti-complement activity of natural triterpenes, chromatographic separation of the EtOAc-soluble fraction from the fruiting body of Ganoderma lucidum led to the isolation of three steroids and five triterpenoids. They were identified as ergosterol peroxide (1), ergosterol (2), genoderic acid Sz (3), stella sterol (4), ganoderic aic C1 (5), ganoderic acid A (6), Methyl ganoderate A (7), and lucidenic acid A (8) based on spectroscopic evidence and physicochemical properties. These compounds were examined for their anti-complement activity against the classical pathway of the complement system. Compounds 2 and 3 showed potent anti-complement activity with IC50 values of 52.0 and 44.6 microM, respectively. Compound 1 exhibited significant inhibitory activity with an IC50 value of 126.8 microM, whereas compounds 4-8 were inactive. Our findings suggested that in addition to the ketone group at C-3, the delta7(8), delta9(11)-lanostadiene type triterpene also plays an important role in inhibiting the hemolytic activity of human serum against erythrocytes.

[Chemical constituents of the spores of Ganoderma lucidum].[Pubmed:18589746]

Zhong Yao Cai. 2008 Jan;31(1):41-4.

OBJECTIVE: To study the chemical constituents of the sporoderm-broken spores of Ganoderma lucidum. METHODS: Chemical constituents were isolated and purified by silica gel and Sephadex LH-20 column chromatography. The structures were identified by means of physicochemical and spectral data. RESULTS: From the ethyl acetate extract of the material, eight compounds were isolated. Their structures were identified as ganoderic acid A (I), Methyl ganoderate A (II), methyl ganoderate B (III), ganoderic acid C2 (IV), ganoderic acid G(V), ergosta-7,22-diene-3beta, 5alpha, 6beta-triol (VI), ergosterol peroxide (VII) and ergosta-7,22-diene-3beta-yl pentadecanoate (VIII), respectively. CONCLUSION: Compounds II, III, VII and VIII are isolated from the spores of G. lucidum for the first time.

Natural inhibitors for protein prenyltransferase.[Pubmed:9619109]

Planta Med. 1998 May;64(4):303-8.

Farnesyl protein transferase (FPT) catalyzes the posttranslational farnesylation of the cysteine residue located in the carboxyl-terminal tetrapeptide of the Ras oncoprotein. Prenylation of this residue is essential for membrane association and cell transforming activities of Ras. Inhibitors of FPT have been demonstrated to inhibit Ras-dependent cell transformation and thus represent a potential therapeutic strategy for the treatment of human cancers (1). In the present study, the inhibitory principles for protein prenyltransferases were isolated and identified from Ganoderma lucidum and garlic. The inhibitors from Ganoderma lucidum were identified as ganoderic acid A and ganoderic acid C by comparison with the reported spectral data. Ganoderic acid A has an IC50 value of 100 microM against FPT and its methyl ester (Methyl ganoderate A) has an IC50 value of 38 microM for the same enzyme. These inhibitors appear to be competitive with farnesyl pyrophosphate (FPP), and Ki values of ganoderic acid A and Methyl ganoderate A are 54 microM and 20 microM, respectively. The inhibitors from garlic were identified as diallyl thiosulfinate (allicin), methyl allyl thiosulfinate, and allyl methyl thiosulfinate. These inhibitors are more effective against geranylgeranyl protein transferase (GGPT) than FPT and IC50 values of allicin, methyl allyl thiosulfinate, and allyl methyl thiosulfinate for GGPT were 43 microM, 57 microM, and 53 microM, respectively. Methyl allyl thiosulfinate appears to be competitive with geranylgeranyl pyrophosphate (GGPP) and its Ki was determined to be 15 microM. The molecular structures of triterpenes and thiosulfinates are expected to be useful in designing lead compounds for new potent antitumour agents.