Meroterpenoids from Ganoderma sinense protect hepatocytes and cardiomyocytes from oxidative stress induced injuries.

Abstract:

:Four meroterpenoids, applanatumols F (1), H (3), I (2), and lingzhiol (4) were isolated from the 95% EtOH extract of the fruiting bodies of Ganoderma sinense. Their structures were established on the basis of NMR spectroscopic analyses, optical rotatory dispersion data, ECD spectra, and X-ray crystallography. Compounds 1, 2, 4 existed as racemic mixtures ((+) 1a, 2a, 4a; (-) 1b, 2b, 4b), while 3 as a single enantiomer. Base on the seperated enantiomers, we sought to explicit possible effects of compounds 1-4 on hydrogen peroxide (H2O2)-induced cell death and to determine their underlying molecular mechanisms in human normal liver LO2 cells. Among them, compound 2a treatment effectively protected LO2 cells against H2O2-induced cell damage and apoptosis. H2O2 exposure increased ROS, which was inhibited by 2a treatment. Mitochondrial membrane potential decrease, nuclear fragments, caspase-3 activation and PARP cleavage were also arrested by 2a. Further, increased levels of Nrf2, HO-1, phosphorylation Akt and up-regulation of antioxidant enzymes were detected in 2a treated cells, indicating that the anti-oxidative effects of 2a might protect LO2 cells against oxidative damage via PI3K/Akt-mediated activation of Nrf2/HO-1 pathway. In addition, compound 2a showed potential protective role of cardiomyocyte from ischemia/reperfusion injury, and pretreatment with 2a could decrease CK and LDH levels and increase GSH level.

journal_name

Fitoterapia

journal_title

Fitoterapia

authors

Gao S,Zhang P,Zhang C,Bao F,Li H,Chen L

doi

10.1016/j.fitote.2018.10.009

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

73-79

eissn

0367-326X

issn

1873-6971

pii

S0367-326X(18)31555-7

journal_volume

131

pub_type

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