Network pharmacology and molecular docking reveal the immunomodulatory mechanism of rhubarb peony decoction for the treatment of ulcerative colitis and irritable bowel syndrome.

Background: Ulcerative colitis (UC) and irritable bowel syndrome (IBS) share various similarities in clinical symptoms, pathogenesis, and treatment. UC concurrent IBS tends toward more severe symptoms and worse prognosis, and promising feasible therapies for the overlapping symptoms remains a challenge. Rhubarb peony decoction (RPD) is a well-known traditional Chinese medicine that has been widely applied in treating UC. RPD may exert extensive therapeutic effects on both IBS and UC. However, the common mechanism of its treatment remains unclear. We aimed to assess the potential pharmacological mechanism of RPD in the treatment of overlapping IBS and UC. Methods: The active components and targets of RPD were retrieved from ETCM, TCMSP, BATMAN-TCM, and TCM databases. The disease targets were screened by searching the DrugBank, OMIM, TTD, and PharmGKB databases. PPI network analysis was performed and visualized via the STRING platform and Cytoscape software. GO and KEGG enrichment analyses of the hub genes of RPD were predicted to elucidate the potential molecular mechanism. Subsequently, molecular docking was carried out to verify the combination of active compounds with core targets. Results: By integrating all targets of RPD and disease, a total of 31 bioactive ingredients were identified including quercetin, kaempferol, aloe-emodin, beta-sitosterol, and (+)-catechin, etc. JUN, TP53, MAPK1, RELA, MYC, and ESR1 were explored as potential therapeutic targets among 126 common drug-disease-related targets. They were enriched in the AGE-RAGE signaling pathway in diabetic complications, as well as the NF-kappa B signaling pathway and MAPK signaling pathway. Additionally, some active ingredients were identified as candidates for binding to the hub targets via molecular docking, further suggesting their anti-inflammatory and antioxidative properties. Conclusion: RPD may exert the overall treatment effect for UC and IBS overlap syndrome via the biological mechanism of "multi-ingredients, multi-targets, and multi-pathways" on inflammation, oxidative stress, immune, oncogenicity, and gut microbiota dysbiosis.

Fucoxanthin Prevents Long-Term Administration l-DOPA-Induced Neurotoxicity through the ERK/JNK-c-Jun System in 6-OHDA-Lesioned Mice and PC12 Cells.

As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin is considered to have neuroprotective activity via its excellent antioxidant properties. Oxidative stress is regarded as an important starting factor for neuronal cell loss and necrosis, is one of the causes of Parkinson's disease (PD), and is considered to be the cause of adverse reactions caused by the current PD commonly used treatment drug levodopa (l-DA). Supplementation with antioxidants early in PD can effectively prevent neurodegeneration and inhibit apoptosis in dopaminergic neurons. At present, the effect of fucoxanthin in improving the adverse effects triggered by long-term l-DA administration in PD patients is unclear. In the present study, we found that fucoxanthin can reduce cytotoxicity and suppress the high concentration of l-DA (200 µM)-mediated cell apoptosis in the 6-OHDA-induced PC12 cells through improving the reduction in mitochondrial membrane potential, suppressing ROS over-expression, and inhibiting active of ERK/JNK-c-Jun system and expression of caspase-3 protein. These results were demonstrated by PD mice with long-term administration of l-DA showing enhanced motor ability after intervention with fucoxanthin. Our data indicate that fucoxanthin may prove useful in the treatment of PD patients with long-term l-DA administration.

Food additive sodium bisulfite induces intracellular imbalance of biothiols levels in NCM460 colonic cells to trigger intestinal inflammation in mice.

Sulfites and other preservatives are considered food additives to prevent pathogen growth in food, and they are generally regarded as safe since the late 1950s. However, the possible effects of sulfites on potential damage to host intestinal tissue remain largely unexplored. Given that endogenous sulfite mainly comes from the metabolism of biothiol, we attempted to clarify the relationship among biothiol levels, gut and food additives sulfite, including sodium bisulfite (NaHSO3), and the possible mechanism of sulfite affecting the intestine. In the present study, the NaHSO3 treatments markedly increased the homocysteine (Hcy) level but decreased the cysteine (Cys) level by promoting the expression of Hcy synthase and inhibiting the activities of cystathionine ß-synthase and cystathionine γ-lyase in NCM460 cells. The level of methionine (Met) was not significantly changed, but NaHSO3 promoted ROS-mediated NF-κB signaling pathway, and increased the expressions of proinflammatory cytokines by regulating the levels of Hcy and Cys in NCM460 cells. Vitamin B6 (VB6) supplementation successfully ameliorated NaHSO3-induced damage in NCM460 cells and the colon of Balb/c mice. Altogether, our study provided valuable insights into the safety evaluation of food preservatives. Besides, VB6 could be used as a promising candidate in novel therapies for sodium bisulfite-induced intestinal inflammation.