Professor Kong Lingyi's team of China Pharmaceutical University published the research results of 4-oi anti-inflammatory mechanism in nature Communications
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Last Update: 2019-12-02
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Source: Internet
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Author: User
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Recently, Professor Kong Lingyi's team from the school of traditional Chinese medicine of China Pharmaceutical University published a study on the anti-inflammatory mechanism of 4-oi The research results were published in nature communications (DOI: 10.1038 / s41467-019-13078-5) with the title of "4-octyl itaconate inhibitors airborne glycollis by targeting GAPDH to exert anti-inflammatory effects" In the key project of National Natural Science Foundation of China "Research on the material basis of Huanglian Jiedu Decoction integrating PK / PD and metabonomics", the author found that the energy metabolism of sepsis rats changed from oxidative phosphorylation to aerobic glycolysis, which confirmed that aerobic glycolysis played an important role in the development of inflammation 4-octylitaconic acid (4-oi) is a derivative of itaconic acid, a small molecule metabolite It has the structure of α, β - unsaturated ketone and can alkylate the sulfhydryl group on the protein The results of protein mass spectrometry showed that 4-oi had direct effect on the 22 sites of cysteine residues on GAPDH, inhibited its enzyme activity and reduced the release of inflammatory factors The metabolic experiments showed that 4-oi blocked glycolysis at GAPDH, decreased the rate of extracellular acidification and increased the oxygen consumption in cells Furthermore, irg1 knockout bmdm cells showed that reducing the production of endogenous itaconic acid could increase the rate of glycolysis and the release of disease factors In the animal model, it is further confirmed that 4-oi can effectively inhibit inflammation This study puts forward new ideas on 4-oi regulation of metabolic reprogramming, and emphasizes the importance of targeted aerobic glycolysis in the treatment of inflammatory diseases, which provides new ideas for the research and development of new anti-inflammatory drugs in the future Dr Liao Shanting and Han Chao, associate professors, are co authors, Prof Kong Lingyi and Prof Wang Junsong are co authors, and China Pharmaceutical University is the first author unit and the first communication unit.
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