The oxygenated products of cryptotanshinone by biotransformation with Cunninghamella elegans exerting anti-neuroinflammatory effects by inhibiting TLR 4-mediated MAPK signaling pathway.

Cryptotanshinone (1), a major bioactive constituent in the traditional Chinese medicinal herb Dan-Shen Salvia miltiorrhiza Bunge, has been reported to possess remarkable pharmacological activities. To improve its bioactivities and physicochemical properties, in the present study, cryptotanshinone (1) was biotransformed with the fungus Cunninghamella elegans AS3.2028. Three oxygenated products (2-4) at C-3 of cryptotanshinone (1) were obtained, among them 2 was a new compound. Their structures were elucidated by comprehensive spectroscopic analysis including HRESIMS, NMR and ECD data. All of the biotransformation products (2-4) were found to inhibit significantly lipopolysaccharide-induced nitric oxide production in BV2 microglia cells with the IC50 values of 0.16-1.16 µM, approximately 2-20 folds stronger than the substrate (1). These biotransformation products also displayed remarkably improved inhibitory effects on the production of inflammatory cytokines (IL-1ß, IL-6, TNF-α, COX-2 and iNOS) in BV-2 cells via targeting TLR4 compared to substrate (1). The underlying mechanism of 2 was elucidated by comparative transcriptome analysis, which suggested that it reduced neuroinflammatory mainly through mitogen-activated protein kinase (MAPK) signaling pathway. Western blotting results revealed that 2 downregulated LPS-induced phosphorylation of JNK, ERK, and p38 in MAPK signaling pathway. These findings provide a basal material for the discovery of candidates in treating Alzheimer's disease.

Terpenoids From the Coral-Derived Fungus Trichoderma harzianum (XS-20090075) Induced by Chemical Epigenetic Manipulation.

The soft coral-derived fungus Trichoderma harzianum (XS-20090075) was found to be a potential strain to produce substantial new compounds in our previous study. In order to explore its potential to produce more metabolites, chemical epigenetic manipulation was used on this fungus to wake its sleeping genes, leading to the significant changes of its secondary metabolites by using a histone deacetylase (HDAC) inhibitor. The most obvious difference was the original main products harziane diterpenoids were changed into cyclonerane sesquiterpenoids. Three new terpenoids were isolated from the fungal culture treated with 10 µM sodium butyrate, including cleistanthane diterpenoid, harzianolic acid A (1), harziane diterpenoid, harzianone E (2), and cyclonerane sesquiterpenoid, 3,7,11-trihydroxy-cycloneran (3), together with 11 known sesquiterpenoids (4-14). The absolute configurations of 1-3 were determined by single-crystal X-ray diffraction, ECD and OR calculations, and biogenetic considerations. This was the first time to obtain cleistanthane diterpenoid and africane sesquiterpenoid from genus Trichoderma, and this was the first chlorinated cleistanthane diterpenoid. These results demonstrated that the chemical epigenetic manipulation should be an efficient technique for the discovery of new secondary metabolites from marine-derived fungi.

Inhibitory activity against tobacco mosaic virus (TMV) replication of pinoresinol and syringaresinol lignans and their glycosides from the root of Rhus javanica var. roxburghiana.

Four new diepoxylignan glycosides, pinoresinol-4'-O-[6' '-O-(E)-feruloyl]-beta-D-glucopyranoside (1), pinoresinol-4'-O-[4' ',6' '-O-(E)-diferuloyl]-beta-D-glucopyranoside (2), pinoresinol-4'-O-[3' ',6' '-O-(E)-diferuloyl]-beta-D-glucopyranoside (3), and syringaresinol- 4'-O-[4' ',6' '-O-(E)-diferuloyl]-beta-D-glucopyranoside (4), together with three known compounds, pinoresinol (5), syringaresinol (6), and pinoresinol-4'-O-beta-D-glucopyranoside (7), were isolated from the n-butanol extract of Rhus javanica var. roxburghiana, and their structures were established using various spectroscopic techniques. Three glycosides (2-4) of the lignans showed moderate inhibition of multiplication of the tobacco mosaic virus.