title: Qifu-Yin attenuates AGEs-induced Alzheimer-like pathophysiological changes through the RAGE/NF-κB pathway.
abstract: Qifu-Yin (QFY), a widely used formula of traditional Chinese medicine (TCM) derived from "Jingyue Quanshu", is one of the most commonly used TCM prescriptions for the clinical treatment of Alzheimer disease. The role of advanced glycation end products (AGEs) and its receptor RAGE have attracted increasing attention as the pivotal role of Aβ has been questioned. The present study was designed to test the neuroprotective effects of QFY, and the possible mechanism in AGE-induced Alzheimer model rats. After injection of AGE in the CA3 area of the hippocampus, QFY (8.6, 4.3, and 2.15 g·kg(-1)), and a positive control drug donepezil (2 mg·kg(-1)) were administrated through gastric intubation to rats once daily for thirty consecutive days. Another positive control group was the AGE + anti-RAGE group, which was simultaneously injected with anti-RAGE antibody before AGE treatment. The control group, sham-operated group, as well as the AGE + anti-RAGE group received saline at the same dosage. The Morris water maze test and the step-down passive avoidance test were conducted to evaluate the cognitive function of the rats. The expression of RAGE and NF-κB were assayed by immunohistochemical staining. The levels of Aβ, TNF-α, and IL-1β in the hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that QFY could significantly attenuate the memory impairment induced by AGE, decrease the expressions of RAGE and NF-κB, and reduce the levels of Aβ, TNF-α, and IL-1β in the hippocampus in a dose-dependent manner. Also, the blockage of RAGE could significantly reduce the impairments caused by AGEs. In conclusion, QFY could attenuate AGEs-induced, Alzheimer-like pathophysiological changes. These neuroprotective effects might be related to the RAGE/NF-κB pathway and its anti-inflammatory activity.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Shu-Yuan
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Shaanxi University of Chinese Medicine, Xianyang 712046, China.
authors.forename: Ji-Ping
authors.initials: JP
authors.lastname: Liu
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Ji
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wen-Jiao
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Key Laboratory of Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China. Electronic address: spma@cpu.edu.cn.
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Ma
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D017127:Glycation End Products, Advanced / Q000009:adverse effects*; D053583:Interleukin-1beta / Q000378:metabolism; D007858:Learning / Q000187:drug effects; D019684:Magnoliopsida; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D008517:Phytotherapy; D010946:Plants, Medicinal; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D017127:Glycation End Products, Advanced; D053583:Interleukin-1beta; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha
keywords: Advanced glycation end products (AGEs); Alzheimer's disease; Qifu-Yin; RAGE