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Sijunzi Decoction (SJZD) is a renowned formula for the treatment of spleen deficiency syndrome (SDS) in traditional Chinese medicine (TCM). Its non-polysaccharides (NPS) component, dominated by various compounds of SJZD, has shown the remarkable efficacy in SDS, especially in gastrointestinal injury. However, the principle of compatibility of SJZD and the micro-mechanism of effect on SDS are still unclear. To elucidate the scientific implications of SJZD compatibility and its micro-mechanism in the treatment of SDS-induced intestinal injury. First, the chemical composition of NPS in SJZD and incomplete SJZD (iSJZD, including SJZD-R, SJZD-A, SJZD-P, SJZD-G) were comprehensively analyzed by UPLC-QTOF-MS, and comparing their chemical composition by multivariate statistical analysis to reveal the effect of a single herb on SJZD compatibility. Second, network pharmacology and molecular docking were used to uncover the micro-mechanisms of potential active compounds in SJZD for the treatment of SDS, and develop an active component combination (ACC) by accurate quantification. Subsequently, the action of the potential active compounds and ACC was verified through in vivo and in vitro. A total of 112, 77, 93, 87, and 67 compounds were detected in NPS of SJZD, SJZD-R, SJZD-A, SJZD-P, and SJZD-G, respectively. Changes in the chemical components of SJZD_NPS and iSJZD_NPS revealed that RG and RAM, as well as RAM and Poria significantly affected the dissolution of each other's chemical components, and the co-decoction of four herbs promoted the dissolution of the active compounds and inhibited toxic compounds. Furthermore, network pharmacology showed that 274 compounds of 15 categories in SJZD_NPS acted on the 186 key targets to treat SDS by inhibiting inflammation, enhancing immunity, and regulating gastrointestinal function and metabolism. Finally, through in vitro experiments, six compounds among 18 potential compounds were verified to markedly repair intestinal epithelium injury by modulating the FAK/PI3K/Akt or LCK/Ras/PI3K/Akt signaling pathway. It is worth mentioning that ACC, composed of 11 compounds accurately quantified, demonstrated significant in vivo treatment effects on intestinal damage with SDS similar to NPS or SJZD. This study elucidates the scientific evidence of the " Jun-Chen-Zuo-Shi " and "detoxification and synergistic" in the decocting process of SJZD. An ACC, the active component of SJZD, ameliorate SDS-induced intestinal injury by the FAK/PI3K/Akt signaling pathway, which provides a strategy for screening alternatives to effective combinations of TCMs. [Display omitted] • Uncovering the principle of "Jun-Chen-Zuo-Shi" and "detoxification and synergistic" of four herbs in SJZD. • Various types of compounds in SJZD_NPS treat SDS through inhibiting inflammation, enhancing immunity, and regulating metabolism and gastrointestinal function. • Six potential active compounds and active component combination repaired the SDS with intestinal injury via modulating FAK/PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Mume Fructus (MF) is processed from the near-ripe fruit of Prunus mume (Siebold) Siebold & Zucc by drying at low temperature until the color turns black. MF is often used in Chinese medicine for the treatment of chronic diarrhea and dysentery. Previous studies have shown that the active components of MF against Crohn's disease (CD) are mainly citrate and hydroxycinnamate derivatives, which can alleviate the CD-induced inflammatory response and intestinal barrier damage. However, their molecular mechanisms on CD still need further elucidation. To investigate the protective effects and underlying mechanisms of citrate and hydroxycinnamate derivatives in MF on intestinal epithelial injury. Network pharmacology technology was used to predict the anti-CD targets and molecular mechanisms of 4 citrate and 11 hydroxycinnamate derivative prototypes and 5 hydroxycinnamate derivative metabolites in the 40% ethanol fraction of MF (MFE40), the active anti-CD ingredient group of MF. Lipopolysaccharide (LPS)-treated IEC-6 cells were used to investigate the effects of the above components on the proliferation of damaged IEC-6 cells and to verify the molecular mechanism of their regulation on the FAK/PI3K/AKT signaling pathways for the promotion of the proliferation of IEC-6 cells. A "compound-target-pathway" network was constructed based on network pharmacology analysis, including 20 citrate and hydroxycinnamate derivatives that target 316 core proteins and 36 CD-related pathways, of which PI3K-AKT pathway and focal adhesion were the most enriched pathways. Further cell validation experiments showed that 1 citric acid (CA) compound and 10 hydroxycinnamate derivatives, including 3- O -caffeoylquinic acid (3CQA), 4- O -caffeoylquinic acid (4CQA), 5- O -caffeoylquinic acid (5CQA), caffeic acid (CFA), p-coumaric acid (PCMA), m-coumaric acid (MCMA), ferulic acid (FUA), isoferulic acid (IFUA), 3-hydroxyphenylpropionic acid (3HPPA) and hippuric acid (HPP), could promote the proliferation of IEC-6 cells and inhibit the damage of LPS to IEC-6 cells. Ethyl caffeate (ECFA), a hydroxycinnamic acid derivative, had no effect on promoting the proliferation of IEC-6 cells and was weak in inhibiting the damage of IEC-6 cells caused by LPS. Further mechanistic verification experiments showed that 7 citrate and hydroxycinnamate derivatives (CA, CFA, 3CQA, MCMA, FUA, 3HPPA, and HPP) could upregulate the expression of p-FAK, p-PI3K, and p-AKT proteins. Among them, CA had the better effect on activating the FAK-PI3K-AKT signaling pathway. Citrate and hydroxycinnamate derivatives in MF can ameliorate LPS-induced intestinal epithelial cell injury to demonstrate potential for Crohn's disease alleviation. This protective effect can be achieved by upregulating FAK/PI3K/AKT pathway. [Display omitted] [ABSTRACT FROM AUTHOR]