Mulberroside A repairs high fructose diet‐induced damage of intestinal epithelial and blood–brain barriers in mice: A potential for preventing hippocampal neuroinflammatory injury
Rong Yu, Shiyu Wen, Qiaona Wang, Congying Wang, Liping Zhang, Xingxin Wu, Jian‐Mei Li, Ling‐Dong Kong
Abstract
Abstract Our previous studies showed that high fructose diet (HFrD)‐driven gut dysbiosis caused fecal short‐chain fatty acids (SCFAs) reduction and intestinal epithelial barrier (IEB) damage in mice, which might play an important role in hippocampal neuroinflammatory injury. Mulberroside A is reported to have neuroprotective effects in animal experiments, while the underlying mechanisms are not yet fully elucidated. Here, we investigated whether and how mulberroside A prevented HFrD‐induced neuroinflammatory injury. HFrD‐fed mice were treated orally with mulberroside A (20 and 40 mg/kg) for 8 weeks. Mulberroside A was found to inhibit hippocampal neuroinflammation and neurogenesis reduction in HFrD‐fed mice. It reshaped gut dysbiosis, increased fecal and serum SCFAs contents, reactivated signaling of the colonic NLR family, pyrin domain containing 6 (NLRP6) inflammasome, and up‐regulated Muc2 expression to prevent IEB damage, as well as subsequently, reduced serum endotoxin levels in this animal model. Additionally, mulberroside A inhibited oxidative stress in colon of HFrD‐fed mice and hydrogen peroxide (H 2 O 2 )‐stimulated Caco‐2 cells. Blood–brain barrier (BBB) structure defects were also observed in HFrD‐driven hippocampal neuroinflammatory injury of mice. Interestingly, mulberroside A maintained astrocyte morphology and up‐regulated tight junction proteins to repair BBB structure defects in hippocampus dentate gyrus (DG). Our results demonstrated that mulberroside A was capable of preventing HFrD‐induced damage of IEB and BBB in mice, which might contribute to the suppression of hippocampal neuroinflammatory injury. image