Baicalin ameliorates heat stress-induced hepatic injury and intestinal microecology dysbiosis in late gestational mice

Abstract

Heat stress (HS) disrupts intestinal microbiota, glycolipid metabolism, and hepatic mitochondrial function in late gestational mice. Baicalin (BAI), a Chinese herbal medicine known for its heat-clearing and anti-inflammatory properties, has shown promise in modulating intestinal microecology and mitigating inflammation in various organs. This study investigates whether baicalin attenuates HS-induced intestinal microbial dysbiosis and liver damage in pregnant mice during late gestation. Twenty-four pregnant mice were randomly assigned to four groups, including thermoneutral (TN) (24 ± 1 ℃), HS (35 ± 1 ℃), HS+BAI200 (oral gavaged with 200 mg/kg BW of BAI), and HS+BAI400 (oral gavaged with 400 mg/kg BW of BAI). 400 mg/kg BAI treatment markedly decreased the rectal temperature and increased fetal weight in HS pregnant mice. Furthermore, 400 mg/kg BAI administration effectively ameliorated HS-induced hepatic damage and lipid disorders, reducing HSP70, AST, and ALT levels while increasing TG concentration. Notably, it activated a network of genes involved in lipid synthesis, including fatty acid synthase ( FAS ), acetyl-CoA carboxylase ( ACC ), and oxidation, such as peroxisome proliferator-activated receptor alpha ( PPARα ), carnitine palmityl transferase 1 beta ( CPT1β ). Moreover, BAI intervention restored the intestinal morphology and barrier function, evidenced by increased intestinal villus height, the ratio of villus height to crypt depth, and colonic goblet cells numbers. 400 mg/kg of BAI treatment up-regulated the expression of tight junction proteins, such as claudin-1 and Zonula Occludens-1 ( ZO-1 ), in the jejunum and ileum, counteracting HS-induced downregulation. High-throughput sequencing showed that BAI treatment altered cecal microbial composition, increasing the relative abundance of beneficial Bacteroidota and decreasing Deferribacterota , Turicibacter , and Akkermansia . Spearman’s correlation analysis highlighted significant correlations between differential cecal microbiota and physiological indexes. In conclusion, BAI administration alleviated adverse impacts in heat-exposed mice during late gestation, improving maternal physiological parameters, and ameliorating hepatic damage with altered cecal microbial composition. The findings suggest that BAI may regulate the gut-liver axis by modulating intestinal morphology, microecology, and hepatic function. Fig . Baicalin administration alleviates heat stress-induced hepatic injury and intestinal microecology dysbiosis in late gestational mice through potential mechanisms. • BAI decreased the rectal temperature and HSP70 level in HS pregnant mice. • BAI ameliorated HS-induced hepatic damage and lipid disorders in late gestational mice. • BAI restored the intestinal morphology and barrier function in HS pregnant mice. • The alleviating effect of baicalin on liver lipid metabolism disorder is related to gut microbiota.

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