Bioactivities Of Chemical Constituents From Ganoderma Duropora And Ganoderma Lucidum Cultivated In Fujian

【Background and Objective】Ganoderma lingzhi,referred to as “Lingzhi” in China,is the most widely recognized and highly evaluated reishi mushroom.There are more than 100 species known in China and other countries of East Asia.Due to the influence of natural climates in different regions,there are certain differences in the active ingredients in different species of Lingzhi from different producing areas.At present,there is a lack of comprehensive research on the compounds of Lingzhi,which is produced from Fujian.In this study,Ganoderma duropora and G.lucidum which circulated in Fujian were selected as the research objects.In order to increase the efficiency of Lingzhi activity development,this study used known activity-directed screening and computer-assisted reverse screening to study the active substances in G.duropora and G.lucidum.This study provides ideas for improving the efficiency of active compounds found in Lingzhi and promotes the development and utilization of active natural drug molecules in Lingzhi.【Methods and Results】(Ⅰ)Study on chemical constituents of G.duropora and G.lucidum.Fivety-nine compounds,including 9 new compounds,were isolated and identified from G.duropora and G.lucidum.Their structures were determined by analyzing MS,spectroscopic and NMR data.Compounds 1-12 were isolated and identified from G.duropora,ingcluding two new farnesyl phenolic compounds,ganoduriporol A(1*)and ganoduriporol B(2*),two new triterpenoids,ganoduritriols A(3*),ganoduritriols B(4*),seven steroids(5-11)and one fatty acid.On the other hand,three new triterpenoids named as lanosta-8,24-dien-26-oic acid,(24E)-3β,11-dihydroxy-7-oxo(32*),7,15-oxolanost-8-ene-3β,25-diol(33*),and 7-oxolanost-8-ene-3β,15α,25-triol(34*),two new farnesyl phenolic compounds named as ganoluciporol A(41*)and ganoluciporol B(42*),twenty-five known triterpenoids(13-31),six known terpenes(43 – 48)and eleven known steroids(49-59)were isolated and identified from G.lucidum.(Ⅱ)Anti-inflammatory activity and mechanism of G.duropora.Anti-inflammatory activities of ganoduriporols A and B(1 and 2)were assayed and evaluated.Ganoduriporols A and B exhibited dose-dependent anti-inflammatory effects in RAW 264.7 cells.Furthermore,ganoduriporol A inhibited the production of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)and prostaglandin E2(PGE2)through the suppression of COX-2,MAPK and NF-κB signaling pathway in LPS-induced macrophage cells.(Ⅲ)Based on the reverse pharmacophore approach,we aligned compounds 2,3,13,15,16,18,25-27,29-35,42,49,53 to human protein targets,from which the top 300 targets were analyzed.By the flexible alignment of these structures the calculated and recorded pharmacophores were obtained and the candidate targets were prioritized,based on the corresponding fit values.As a reuslt,10 proteins,steryl-sulfatase,aldose reductase,mitogen-activated protein kinase-10,bone morphogenetic protein 2,and purine nucleoside phosphorylase,were screened out,that provided a reference for the study of the active ingredients in Ganoderma.【Conclusion】In conclusion,9 new compounds and 50 known compounds have been isolated from G.duropora and G.lucidum cultivated in Fujian,including the structural types of triterpenoids,steroids,triterpenes,and fatty acids.Our rearch lays the foundation for the construction of a chemical library of Ganoderma.Anti-inflammatory activity study results suggested that two new farnesyl phenolic compounds(1 and 2)and the fruiting body of G.duropora could serve as anti-inflammatory agents for medicinal use or functional food.The target of natural products can be predicted by reverse-docking.This use in combination with ancient eastern and modern databases is a fast and easy way to find drug candidates.