Characterizing the specific mechanism of series processed Coptidis Rhizoma by multi-organ metabolomics combined with network pharmacology and molecular docking.

BACKGROUND:After being processed with different excipients, the clinical application of Coptidis Rhizoma (CR) is differentially investigated. However, the underlying mechanism and material basis are not clear, and there is a lack of attention to the collaborative working mode of herbal medicine during exploration. PURPOSE:To characterize the specific mechanism of wine/zingiberis rhizoma recens/euodiae fructus processed CR (wCR/zCR/eCR) and to investigate the role of excipients during processing. METHODS:The multi-organ metabolomics approach was employed to explore the target organs of wCR/zCR/eCR and multiple pathways being triggered in each organ. The tissue distribution of CR and wCR/zCR/eCR components was compared to indicate the material basis of efficacy change after processing. Further, the network pharmacology study coupled with experimental validation was conducted to support metabolomic research and predicted active ingredients and core targets, and the molecular docking coupled with binding test was performed to identify the binding between active ingredient and core target. RESULTS:The multi-organ metabolomics and network pharmacology study elucidated the intervening effect of wCR on heart/lung, zCR on stomach/colon, and eCR on liver/colon/stomach. Combined with molecular docking, binding test and tissue distribution studies, the specific mechanism was as follows: the wine made iso-quinoline alkaloids in CR more likely to accumulate in heart/lung, thus triggering the core targets of PTGS2, NOS2, ESR1 and SLC6A4 in heart/lung, and thereby highlighting the detoxifying and cardiopulmonary protective effect of wCR. The zingiberis rhizoma recens and euodiae fructus made organic acids in CR more likely to accumulate in stomach/colon and liver/colon/stomach respectively, thus triggering the core targets of ACTB, TNF and PRKCA in stomach/colon, the core targets of ACTB, TNF, PRKCA and GPT in stomach/colon/liver, and thereby highlighting the improving effect of zCR/eCR on digestive function. CONCLUSION:Iso-quinoline alkaloids were the material basis of CR for anti-inflammation, and organic acids were mainly responsible for regulating gastrointestinal function. Due to the influence of excipients on the accumulation tendency of CR components, the differentially highlighted application of wCR/zCR/eCR was achieved. These findings propose a novel strategy for processing mechanism research.