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Protective effects of Commiphora erythraea resin constituents against cellular oxidative damage.

ABSTRACT: By bioguided fractionation of the hexane extract of Commiphora erythraea resin we isolated four furanosesquiterpenoids that were tested for their protective activity against oxidative stress. Furanodienone and 1,10(15)-furanogermacra-dien-6-ones showed to be potent inhibitors of lipid peroxidation (IC(50) of -0.087 ?M), being more active than the methoxylated analogues. Furthermore, using BV2 microglial cells, we found that furanodienone from C. erythraea is able to counteract LPS-induced cell death and decrease LPS-induced NO generation thus protecting microglial cells from LPS-induced cytotoxicity. Finally, docking studies were undertaken to gain insight into the possible binding mode of the isolated compounds at 5-LOX binding site.

SUBMITTER: Marcotullio MC

PROVIDER: S-EPMC6264320 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Protective effects of Commiphora erythraea resin constituents against cellular oxidative damage.

Marcotullio Maria Carla MC Messina Federica F Curini Massimo M Macchiarulo Antonio A Cellanetti Marco M Ricci Donata D Giamperi Laura L Bucchini Anahi A Minelli Alba A Mierla Anna Lisa AL Bellezza Ilaria I

Molecules (Basel, Switzerland) 20111214 12

By bioguided fractionation of the hexane extract of Commiphora erythraea resin we isolated four furanosesquiterpenoids that were tested for their protective activity against oxidative stress. Furanodienone and 1,10(15)-furanogermacra-dien-6-ones showed to be potent inhibitors of lipid peroxidation (IC(50) of -0.087 μM), being more active than the methoxylated analogues. Furthermore, using BV2 microglial cells, we found that furanodienone from C. erythraea is able to counteract LPS-induced cell d ...[more]

PMID: 22169939

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Project description:Background: The present study was designed to investigate the protective effects and mechanisms of carnosine on lipopolysaccharide (LPS)-induced injury in Caenorhabditis elegans.Methods: C. elegans individuals were stimulated for 24?h with LPS (100??g/mL), with or without carnosine (0.1, 1, 10?mM). The survival rates and behaviors were determined. The activities of superoxide dismutase (SOD), glutathione reductase (GR), and catalase (CAT) and levels of malondialdehyde (MDA) and glutathione (GSH) were determined using the respective kits. Reverse transcription polymerase chain reaction (RT-PCR) was performed to validate the differential expression of sod-1, sod-2, sod-3, daf-16, ced-3, ced-9, sek-1, and pmk-1. Western blotting was used to determine the levels of SEK1, p38 mitogen-activated protein kinase (MAPK), cleaved caspase3, and Bcl-2. C. elegans sek-1 (km2) mutants and pmk-1 (km25) mutants were used to elucidate the role of the p38 MAPK signaling pathway.Results: Carnosine improved the survival of LPS-treated C. elegans and rescued behavioral phenotypes. It also restrained oxidative stress by decreasing MDA levels and increasing SOD, GR, CAT, and GSH levels. RT-PCR results showed that carnosine treatment of wild-type C. elegans up-regulated the mRNA expression of the antioxidant-related genes sod-1, sod-2, sod-3, and daf-16. The expression of the anti-apoptosis-related gene ced-9 and apoptosis-related gene ced-3 was reversed by carnosine. In addition, carnosine treatment significantly decreased cleaved caspase3 levels and increased Bcl-2 levels in LPS-treated C. elegans. Apoptosis in the loss-of-function strains of the p38 MAPK signaling pathway was suppressed under LPS stress; however, the apoptotic effects of LPS were blocked in the sek-1 and pmk-1 mutants. The expression levels of sek-1 and pmk-1 mRNAs were up-regulated by LPS and reversed by carnosine. Finally, the expression of p-p38MAPK and SEK1 was significantly increased by LPS, which was reversed by carnosine.Conclusion: Carnosine treatment protected against LPS injury by decreasing oxidative stress and inhibiting apoptosis through the p38 MAPK pathway.

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Protective effects of Commiphora erythraea resin constituents against cellular oxidative damage.

Publications

Protective effects of Commiphora erythraea resin constituents against cellular oxidative damage.

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