title: Chronic rhein treatment improves recognition memory in high-fat diet-induced obese male mice.
abstract: 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.
authors: 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.
authors: Sen
authors: S
authors: Wang
authors: 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.
authors: Xu-Feng
authors: XF
authors: Huang
authors: School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia; Department of Pathogen Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors: Peng
authors: P
authors: Zhang
authors: 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.
authors: Hongqin
authors: H
authors: Wang
authors: School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
authors: Qingsheng
authors: Q
authors: Zhang
authors: 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. Electronic address: yushijia723@hotmail.com.
authors: Shijia
authors: S
authors: Yu
authors: 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. Electronic address: yinghua@uow.edu.au.
authors: Yinghua
authors: Y
authors: Yu
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D064806:Dysbiosis / Q000209:etiology / Q000382:microbiology / Q000517:prevention & control*; D019446:Endotoxemia / Q000209:etiology / Q000517:prevention & control; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D018149:Glucose Intolerance / Q000209:etiology / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D009443:Neuritis / Q000209:etiology / Q000517:prevention & control; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018697:Nootropic Agents / Q000627:therapeutic use*; D009765:Obesity / Q000178:diet therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D000071039:Perirhinal Cortex / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D021641:Recognition, Psychology
chemical_list: D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D019440:Anti-Obesity Agents; D019208:Brain-Derived Neurotrophic Factor; D005765:Gastrointestinal Agents; D018697:Nootropic Agents; C020491:rhein
keywords: Gut microbiota; Inflammation; Lipopolysaccharide; Perirhinal cortex; Recognition memory; Rhein