Novel applications of Yinhua Miyanling tablets in ulcerative colitis treatment based on metabolomics and network pharmacology.

BACKGROUND: Yinhua Miyanling tablets (YMT), comprising 10 Chinese medicinal compounds, is a proprietary Chinese medicine used in the clinical treatment of urinary tract infections. Medicinal compounds, extracts, or certain monomeric components in YMT all show good effect on ulcerative colitis (UC). However, no evidence supporting YMT as a whole prescription for UC treatment is available. PURPOSE: To evaluate the anti-UC activity of YMT and elucidate the underlying mechanisms. The objective of the study was to provide evidence for the add-on development of YMT to treat UC. METHODS: First, YMT's protective effect on the intestinal barrier was evaluated using a lipopolysaccharide (LPS)-induced Caco-2 intestinal injury model. Second, the UC mouse model was established using dextran sodium sulfate (DSS) to determine YMT's influence on symptoms, inflammatory factors, intestinal barrier, and histopathological changes in the colon. Third, an integrated method combining metabolomics and network pharmacology was employed to screen core targets and key metabolic pathways with crucial roles in YMT's therapeutic effect on UC. Molecular docking was employed to identify the key targets with high affinity. Finally, western blotting was performed to validate the mechanism of YMT action against UC. RESULTS: YMT enhanced the transepithelial electrical resistance value and improved the expression of proteins of the tight junctions dose-dependently in LPS-induced Caco-2 cells. UC mice treated with YMT exhibited alleviated pathological lesions of the colon tissue in the in vivo pharmacodynamic experiments. The colonic lengths tended to be normal, and the levels of inflammatory factors (TNF-α, IL-6, and iNOS) along with those of the core enzymes (MPO, MDA, and SOD) improved. YMT effectively ameliorated DSS-induced colonic mucosal injury; pathological changes along with ultrastructure damage were significantly alleviated (evidenced by a relatively intact colon tissue, recovery of epithelial damage, repaired gland, reduced infiltration of inflammatory cells and epithelial cells arranged closely with dense microvilli). Seven key targets (IL-6, TNF-α, MPO, COX-2, HK2, TPH, and CYP1A2) and four key metabolic pathways (arachidonic acid metabolism, linoleate metabolism, glycolysis, and gluconeogenesis and tyrosine biosynthesis) were identified to play vital roles in the treatment on UC using YMT. CONCLUSIONS: YMT exerts beneficial therapeutic effects on UC by regulating multiple endogenous metabolites, targets, and metabolic pathways, suggestive of its potential novel application in UC treatment.

(-)-Syringaresinol attenuates ulcerative colitis by improving intestinal epithelial barrier function and inhibiting inflammatory responses.

BACKGROUND: (-)-Syringaresinol (SYR), a natural lignan with significant antioxidant and anti-inflammatory activities, possesses various pharmacological benefits including cardio-protective, antibacterial, anticancer, and anti-aging effects. It was shown that the effectiveness of (+)-syringaresinol diglucoside on the ulcerative colitis (UC) was attributed to the active metabolite (+)-syringaresinol (the enantiomor of SYR). However, the efficacy of SYR against UC remains unclear, and the associated molecular mechanism has not been revealed yet PURPOSE: This study aimed to assess the protective effect of SYR in UC and its underlying mechanism STUDY DESIGN AND METHODS: We examined SYR's protective impact on the intestinal epithelial barrier and its ability to inhibit inflammatory responses in both a lipopolysaccharide (LPS)-induced Caco-2 cell model and a dextran sodium sulfate (DSS)-induced UC mouse model. We also explored the potential signaling pathways regulated by SYR using transcriptome analysis and western blot assay RESULTS: In Caco-2 cells, SYR significantly increased trans-epithelial electrical resistance, reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ), and cyclooxygenase-2 (COX-2) levels, and enhanced cellular tight junction protein expression and distribution. In mice with UC, oral treatment with SYR (10, 20, 40 mg·kg-1) dose-dependently increased body weight, colon length, and expression of tight junction proteins, decreased disease activity index score, spleen coefficient, cytokine serum levels, bacterial translocation, and intestinal damage, and also preserved the ultrastructure of colonic mucosal cells. Transcriptomics indicated that the anti-UC effect of SYR is mediated via the PI3K-Akt/MAPK/Wnt signaling pathway. CONCLUSION: In summary, SYR effectively mitigated the development of UC by enhancing the intestinal epithelial barrier function and attenuating the inflammatory response. The plant-derived product SYR might be a potentially effective therapeutical agent against UC.

Protective effect of total Saponins from American ginseng against cigarette smoke-induced COPD in mice based on integrated metabolomics and network pharmacology.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disease. Aiming at assessing the effect of total saponins from American ginseng on COPD, both the chemical composition and anti-COPD activity of total saponins from wild-simulated American ginseng (TSW) and field-grown American ginseng (TSF) were investigated in this study. Firstly, a HPLC-ELSD chromatographic method was established to simultaneously determine the contents of 22 saponins in TSW and TSF. Secondly, CS-induced COPD mouse model was established to evaluate the activity of TSW and TSF. The results indicated that both TSW and TSF had the protective effect against COPD by alleviating oxidative stress and inflammatory response. TSW showed a stronger effect than TSF. Thirdly, an integrated approach involving metabolomics and network pharmacology was used to construct the "biomarker-reaction-enzyme-target" correlation network aiming at further exploring the observed effects. As the results, 15 biomarkers, 9 targets and 5 pathways were identified to play vital roles in the treatment of TSW and TSF on COPD. Fourthly, based on network pharmacology and the CS-stimulated A549 cell model, ginsenoside Rgl, Rc, oleanolic acid, notoginsenoside R1, Fe, silphioside B were certified to be the material basis for the stronger effect of TSW than TSF. Finally, the molecular docking were performed to visualize the binding modes. Our findings suggested that both TSW and TSF could effectively ameliorate the progression of COPD and might be used for the treatment of COPD.