Ameliorative Effects of Schisandrol A on Lipopolysaccharide-Induced Intestinal Injury in Mice.

Schisandra chinensis (Turcz.) Baill. is a traditional medicinal and edible plant abundant in bioactive constituents which has been proven to exert prominent intestinal protective effects. Schisandrol A (SA) is one of the lignan components with a relatively high content in this plant. This study aims to evaluate the intestinal protective effects of schisandrol A (SA) in a lipopolysaccharide (LPS)-induced intestinal injury mouse model. An LPS-induced mouse model was established and treated with SA in different groups, and oxidative stress, inflammatory markers, apoptosis, NF-κB signaling pathway proteins, and tight junction proteins were examined. Meanwhile, 16S rRNA gene sequencing and serum metabolomics were employed to evaluate alterations in the gut microbiota and host serum biochemical profiles. The results showed that SA significantly alleviated LPS-induced intestinal injury. SA attenuated oxidative stress, upregulated the anti-inflammatory cytokine IL-10, and reduced the levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. In addition, SA inhibited apoptosis and the activation of the NF-κB pathway, while upregulating the expression of the tight junction proteins ZO-1 and occludin. Gut microbiota analysis revealed that SA reversed the LPS-induced gut microbiota dysbiosis. Serum metabolomics indicated that SA exerted its intestinal protective effects by targeting and modulating several core host serum biochemical pathways. In conclusion, SA reduces oxidative stress and inflammatory responses, restores the intestinal barrier, reshapes the gut microbiota, improves disturbed serum biochemical profiles, and inhibits the activation of the NF-κB pathway, thereby effectively ameliorating intestinal injury in mice.