Direct determination of E and Z configurations for double bond in bioactive meroterpenoids from Ganoderma mushrooms by diagnostic 1H NMR chemical shifts and structure revisions of previous analogues.

[Display omitted] • Six new meroterpenoids and three known compounds were isolated from Ganoderma mushrooms. • The chemical shift of H-8 was used to revised the structures of previous reported meroterpenoids. • Cochlearin I was found to be a potent selective inhibitor of Smad3 phosphorylation. • Ganomycin C and ganodercin D could increase glucose uptake in a dose dependent manner. • Ganomycin C and ganodercin D was found to activate the phosphorylation of AKT (Ser-473). Ganoderma mushrooms are not only traditional Chinese medicine, but also dietary supplements and functional foods worldwide. In this work, six new meroterpenoids, ganodercins A − F (2 , 3 , and 6 – 9), and three known compounds ganomycin C (1), cochlearin I (4), and fornicin D (5) were isolated from Ganoderma mushrooms. An approach characteristic of the chemical shift for H-8 to assign the geometry of meroterpenoids was developed and successfully used for structure revisions of 1 , 5 , and previous analogues. Biological evaluation found that 4 selectively inhibits Smad3 phosphorylation in TGF- β 1-induced NRK-52E cells. Moreover, 1 and 7 could increase glucose uptake in a dose dependent manner in palmitic acid induced C2C12 cells. Further, 1 was found to activate AMPKα(Thr-172) and AKT(Ser-473) phosphorylation, while 7 could activate AKT(Ser-473) phosphorylation. This study demonstrates the potential of Ganoderma to be developed as new anti-renal fibrosis and improve insulin resistance functional food and medicine. [ABSTRACT FROM AUTHOR]