Effects Of Coptis Chinensis In The Treatment Of Type 2 Diabetes Mellitus And Its Multi-component And Multi-target Molecular Mechanism Based On Reverse Molecular Docking Theory

OBJECTIVE: To study the effect substance group of Huanglian in the treatment of type 2 diabetes mellitus(T2DM)and to explore the molecular mechanism of its multi-component and multi-target.METHODS: The reverse molecular docking technique was used to explore the effective components of Coptis chinensis in the treatment of T2 DM.At the same time,the mRNA and protein levels of the effector components and differential proteins were tested from the cell layer to further verify the multi-target of the Coptis effector group in the treatment of T2 DM.Its multi-components and molecular mechanisms were also explored.RESULTS: 789 quantitative proteins with quantitative information were identified by quantitative proteomic analysis.According to their expression levels and literature screening,65 species closely related to T2 DM were selected and reversed docking calculations with various effect substances of Coptis.Finally,14 proteins with relatively good binding(Pla2g7,G6 PD,PSMA6,C4,C2,APOC3,APOC1,PRDX2,PKM2,APOE,GPX3,IGF-1,IGFBP4,IGFBP6)were identified.Five active constituents of Coptis chinensis were also identified(Berberine,coptisine,epiberberine,palmatine,Jatrorrhizine).Five effective substances of Coptis chinensis were used to interfere with HepG2 cells cultured in high glucose and high fat medium,respectively.The results of PCR and Western Blot showed that all five substances of Coptis chinensis could produce effects on 10 of these 14 target proteins(G6PD,PSMA6,PRDX2,PKM2,GPX3,IGF-1,IGFBP4,IGFBP6,APOC1,APOE).Among them,8(G6PD,PSMA6,PRDX2,PKM2,GPX3,IGFQ1,IGFBP4,IGFBP6)were up-regulated,while two targets(APOC1,APOE)were down-regulated.CONCLUSION: This study revealed the functional information of the bioactive components of Coptis chinensis in the treatment of T2 DM,and verified 14 targets of Coptis chinensis in the treatment of T2 DM.It also proved that the five main components of Coptis chinensis(berberine,coptisine,Jatrorrhizine,epiberberine and palmatine)might be the effective components of these targets,especially berberine,Jatrorrhizine and berberine.It was suggested that the mechanism of action might be related to directly or indirectly promoting the activity of antioxidant enzymes and reducing the damage of hepatic cells under oxidative stress,thereby leading to the improvement of insulin resistance.