Lianweng Granules Alleviate Intestinal Barrier Damage via the IL-6/STAT3/PI3K/AKT Signaling Pathway with Dampness-Heat Syndrome Diarrhea.

Dampness-heat syndrome diarrhea (DHSD) is a common clinical disease with a high prevalence but still has no satisfactory therapeutic medicine, so the search for a safe and effective drug candidate is ongoing. This study aims to explore the efficacy and mechanisms of Lianweng granules (LWG) in the treatment of DHSD and to identify the blood transport components of LWG. We assessed the efficacy of LWG in DHSD by various in vivo metrics such as body weight, disease activity index (DAI), histopathologic examination, intestinal barrier function, levels of inflammatory, apoptotic biomarkers, and oxidative stress. We identified the blood components of LWG using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS), and the resolved key components were used to explore the relevant targets. We next predicted the potential mechanisms of LWG in treating DHSD using network pharmacology and molecular docking based on the relevant targets. Finally, the mechanisms were validated in vivo using RT-qPCR, Western blotting, ELISA, and immunofluorescence and evaluated in vitro using Cell Counting Kit-8 (CCK-8), small interfering RNA, cellular enthusiasm transfer assay (CETSA), and drug affinity response target stability (DARTS). Ninety-one pharmacodynamic components of LWG enter the bloodstream and exert possible therapeutic effects. In vivo, LWG treatment improved body weight, reduced colonic injury and DAI scores, lowered inflammation, oxidative stress, and apoptosis markers, and partially restored intestinal barrier function in DHSD mice. Guided by network pharmacology and molecular docking, it is suggested that LWG may exert therapeutic effects by inhibiting IL-6/STAT3/PI3K/AKT signaling. LWG significantly decreased the expression of IL-6, p-STAT3, p-PI3K, p-AKT, and other proteins. These findings were supported by in vitro experiments, where CETSA, DARTS, and siRNA evidenced LWG's targeting of STAT3. LWG targeted STAT3 to inhibit inflammation, oxidative stress, and apoptosis in the colon, thereby restoring the intestinal barrier function to some extent and exerting a therapeutic effect on DHSD.

Qingjie decoction attenuated E.coli-induced diarrhea by regulating energy metabolism and alleviating inflammation based on network analysis and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Diarrhea is a frequently encountered gastrointestinal complication in clinical practice, and E. coli is one of the main causative agents. Although Qingjie decoction (QJD) has been shown to be highly effective in treating diarrhea by eliminating heat-toxin, the underlying molecular mechanisms and pathways of QJD remain unclear. AIM OF REVIEW: The aim of this research was to explore the effects and fundamental mechanism of QJD on diarrhea induced by E.coli in rats. MATERIALS AND METHODS: Initially, we used UHPLC-MS/MS analysis to identify the chemical composition of QJD. Then, we constructed a visualization network using network pharmacology. Next, we utilized metabolomics to identify differentially expressed metabolites of QJD that are effective in treating diarrhea. RESULTS: The chemical composition of QJD was analyzed using UHPLC-MS/MS, which identified a total of 292 components. Using a network pharmacology approach, 127 bioactive compounds of QJD were screened, targeting 171 potential diarrhea treatment targets. TNF-α, IL-6, IL-1ß, and CAT were identified as important targets through visualizing the PPI network. Enrichment analysis demonstrated significant enrichment in the TNF signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. QJD showed beneficial effects, such as increased body weight, decreased fecal water content, and reduced inflammatory cell infiltration in the duodenum and colon, as well as maintaining the structure of the duodenum and colon. Metabolomic analysis revealed 32 differentially expressed metabolites in the control, model and QJD-H groups, including glucose, valine, and cysteine. Functional analysis indicated that differential metabolites were related to energy metabolism, including glucose metabolism, TCA cycle, and amino acid metabolism. CONCLUSION: QJD significantly increased body weight, decreased water content in feces, relieved inflammatory cell infiltration, maintained the structure of duodenum and colon. Combining network analysis and metabolomics, QJD exerted therapeutic effects by inhibiting inflammation and oxidative stress, regulating glucose metabolism, tricarboxylic acid metabolism, and amino acid metabolism.

Anti-MMP-2 and MMP-9 activity of Salsola komarovii Iljin extract and its solvent fractions

Objective: To investigate matrix metalloproteinases (MMP)-2 and MMP-9 inhibitory effect of Salsola komarovii Iljin, an edible halophyte with health beneficial effects. Methods: Salsola komarovii crude extracts (SKI), and solvent (n-hexane, 85% aq. MeOH, n-BuOH, and H