Rehmannia glutinosa polysaccharides attenuates colitis via reshaping gut microbiota and short-chain fatty acid production.

BACKGROUND: Ulcerative colitis is a gastrointestinal disease closely related to intestinal epithelial barrier damage and intestinal microbiome imbalance; however, effective treatment methods are currently limited. Rehmannia glutinosa polysaccharide (RGP) is an important active ingredient with a wide range of pharmacological activities, although its protective effect on colitis remains to be explored. In the present study, we verified the in vitro anti-inflammatory effect of RGP, and observed the ameliorating effect of RGP on dextran sulfate sodium-induced colitis in mice. RESULTS: The results showed that (i) RGP attenuates lipopolysaccharide-induced overexpression of inflammatory factors in RAW264.7 cells; (ii) RGP improves the pathological damage caused by DSS, including weight loss, increased disease activity index and intestinal tissue ulcers; (iii) RGP improves tight junction proteins to protects the tightness of the intestinal epithelium; (iv) RGP inhibits the expression of inflammatory factors through the nuclear factor-kappa B pathway, and improved the of intestinal tissues inflammation; and (v) RGP can maintain the species diversity of intestinal microbes, increase the content of short-chain fatty acids and then restore the imbalance of intestinal microecology. CONCLUSION: RGP can improve the intestinal microbiota to strengthen the intestinal epithelial barrier and protect against DSS-induced colitis. © 2022 Society of Chemical Industry.

Oleanolic acid improved intestinal immune function by activating and potentiating bile acids receptor signaling in E. coli-challenged piglets.

BACKGROUND: Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases. Oleanolic acid (OA) is a pentacyclic triterpene that is ubiquitous in plants. Our previous work demonstrated the protective effect of OA on intestinal health, but the underlying molecular mechanisms remain unclear. This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli (ETEC) in piglets. The key molecular role of bile acid receptor signaling in this process has also been explored. RESULTS: Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets (P < 0.05). OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum (P < 0.05). This may also explain why OA can maintain the stability of the intestinal microbiota structure in ETEC-challenged piglets. In addition, as a natural ligand of bile acid receptors, OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptors TGR5 and FXR (P < 0.05). Specifically, OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream cAMP-PKA-CREB signaling pathway (P < 0.05). Furthermore, OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR (P < 0.05), thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells. CONCLUSIONS: In conclusion, our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response, which provides a new diet-based intervention for intestinal diseases caused by pathogenic bacterial infections in piglets.

Protective effects of sinomenine hydrochloride on lead-induced oxidative stress, inflammation, and apoptosis in mouse liver.

Lead, one of the most common heavy metal toxins, seriously affects the health of humans and animals. Sinomenine hydrochloride (SH) shows antioxidative, anti-inflammatory, antiviral, and anticancer properties. Hence, this study investigated the protective effects of SH against Pb-induced liver injury and explored the underlying mechanisms. First, a mouse model of lead acetate (0.5 g/L lead acetate in water, 8 weeks) was established, and SH (100 mg/kg bw in water, 8 weeks) intervention was administered by gavage. Then, the protective effect of SH against lead-induced liver injury was evaluated through serum biochemical analysis, histopathological analysis, and determination of malondialdehyde (MDA) and total antioxidant capacity (T-AOC) levels. The messenger RNA (mRNA) expression levels of the cytokines IL-1ß and TNF-α and the apoptosis factors Bax, Bcl-2, and Caspase3 in the liver were detected by quantitative real-time PCR. Then, the expression levels of IL-1ß and TNF-α in the liver were detected by ELISA. Immunohistochemical determination of the expression of the apoptosis factors Bax, Bcl-2, and Caspase3 was performed. SH treatment reduced the levels of liver alanine aminotransferase, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and MDA in Pb-treated mice, indicating that SH protected the liver from injury and oxidative stress in Pb-treated mice. SH also increased the liver T-AOC of Pb-treated mice. Quantitative real-time PCR, ELISA, and immunohistochemical analysis showed that SH inhibited apoptosis, as indicated by the regulation of the mRNA expression of Bax and Bcl-2 and the reduced expression of Caspase3 and pro-inflammatory factors (IL-1ß and TNF-α) in the livers of Pb-treated mice. These results suggest that SH protects the mouse liver from Pb-induced injury. The underlying mechanism involves antioxidative, anti-inflammatory, and anti-apoptotic processes.