School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia; Department of Endocrinology and Metabolism, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110032, China.
School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia; Schizophrenia Research Institute, NeuRA, Barker Street Randwick, Sydney, NSW 2031, Australia.
J Nutr Biochem. 2016 Oct;36:42-50. doi: 10.1016/j.jnutbio.2016.07.008. Epub 2016 Aug 4.
High-fat (HF) diet modulates gut microbiota and increases plasma concentration of lipopolysaccharide (LPS) which is associated with obesity and its related low-grade inflammation and cognitive decline. Rhein is the main ingredient of the rhubarb plant which has been used as an anti-inflammatory agent for several millennia. However, the potential effects of rhein against HF diet-induced obesity and its associated alteration of gut microbiota, inflammation and cognitive decline have not been studied. In this study, C57BL/6J male mice were fed an HF diet for 8 weeks to induce obesity, and then treated with oral rhein (120 mg/kg body weight/day in HF diet) for a further 6 weeks. Chronic rhein treatment prevented the HF diet-induced recognition memory impairment assessed by the novel object recognition test, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits in the perirhinal cortex. Furthermore, rhein inhibited the HF diet-induced increased plasma LPS level and the proinflammatory macrophage accumulation in the colon and alteration of microbiota, including decreasing Bacteroides-Prevotella spp. and Desulfovibrios spp. DNA and increasing Bifidobacterium spp. and Lactobacillus spp. DNA. Moreover, rhein also reduced body weight and improved glucose tolerance in HF diet-induced obese mice. In conclusion, rhein improved recognition memory and prevented obesity in mice on a chronic HF diet. These beneficial effects occur via the modulation of microbiota, hypoendotoxinemia, inhibition of macrophage accumulation, anti-neuroinflammation and the improvement of BDNF expression. Therefore, supplementation with rhein-enriched food or herbal medicine could be beneficial as a preventive strategy for chronic HF diet-induced cognitive decline, microbiota alteration and neuroinflammation.
高脂（HF）饮食会改变肠道微生物群，并增加内毒素（LPS）的血浆浓度，而内毒素与肥胖及其相关的低度炎症和认知能力下降有关。大黄酸是大黄植物的主要成分，几千年来一直被用作抗炎剂。然而，大黄酸对 HF 饮食诱导的肥胖及其相关的肠道微生物群改变、炎症和认知能力下降的潜在影响尚未得到研究。在这项研究中，C57BL/6J 雄性小鼠喂食 HF 饮食 8 周以诱导肥胖，然后用口服大黄酸（HF 饮食中 120mg/kg 体重/天）进一步治疗 6 周。慢性大黄酸治疗可预防 HF 饮食诱导的识别记忆障碍，通过新物体识别试验评估，HF 饮食诱导的边缘皮层神经炎症和脑源性神经营养因子（BDNF）缺陷。此外，大黄酸抑制了 HF 饮食诱导的血浆 LPS 水平升高和结肠中促炎巨噬细胞的积累以及微生物群的改变，包括减少拟杆菌属-普雷沃氏菌属和脱硫弧菌属 DNA 并增加双歧杆菌属和乳杆菌属 DNA。此外，大黄酸还降低了 HF 饮食诱导肥胖小鼠的体重和改善了葡萄糖耐量。总之，大黄酸改善了慢性 HF 饮食诱导肥胖小鼠的识别记忆能力。这些有益作用是通过调节微生物群、低内毒素血症、抑制巨噬细胞积累、抗神经炎症和改善 BDNF 表达来实现的。因此，补充富含大黄酸的食物或草药可能是预防慢性 HF 饮食诱导的认知能力下降、微生物群改变和神经炎症的有益策略。
