Paeoniflorin ameliorates cognitive dysfunction via regulating SOCS2/IRS-1 pathway in diabetic rats.
Paeoniflorin is a natural monoterpene glycoside in Paeonia lactiflora pall with various biological properties including promising anti-inflammatory activity. Current evidences support that inflammatory reaction, oxidative stress, as well as abnormal insulin signaling in the hippocampus are potential causes of tau hyperphosphorylation and finally induce cognitive dysfunction. The present study aims to explore the effects of paeoniflorin on the cognitive deficits and investigate the underlying mechanisms in diabetic rats induced by a high-sucrose, high-fat diet and low dose of streptozotocin (STZ). Paeoniflorin treatment effectively improved the performance of diabetic rats in the Morris water maze test via decreasing escape latency and increasing the spent time in the target quadrant. Immunohistochemistry staining also had shown that tau hyperphosphorylation in the hippocampus was prevented after paeoniflorin administration. This function was correlated with its abilities of reducing the brain inflammatory cytokines (IL-1β and TNF-α), decreasing suppressor of cytokine signaling 2 (SOCS2) expressions and promoting insulin receptor substrate-1 (IRS-1) activity. Additionally, we also found paeoniflorin administration significantly promoted the phosphorylation levels of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β). Together, these results showed that paeoniflorin had beneficial effects on relieving diabetes-associated cognitive deficits via regulating SOCS2/IRS-1 pathway and might provide a feasible method for the treatment of diabetes-associated cognitive dysfunction.
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198, China.
Xiaoxu
X
Sun
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198, China.
Shanshan
S
Li
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198, China.
Lixing
L
Xu
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198, China.
Hao
H
Wang
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198, China.
Zhanqiang
Z
Ma
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198, China.
Qiang
Q
Fu
Department of Pharmacology of Traditional Chinese Medical Formulae, Nanjing University of Traditional Chinese Medicine, 138, Xianlin Road, Nanjing 210029, China.
Rong
R
Qu
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198, China. Electronic address: spma@cpu.edu.cn.
Shiping
S
Ma
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D039821:Monoterpenes / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism; D006027:Glycosides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D016207:Cytokines; D005960:Glucosides; D055504:Insulin Receptor Substrate Proteins; D039821:Monoterpenes; D050826:Suppressor of Cytokine Signaling Proteins; D016875:tau Proteins; C526296:Irs1 protein, rat; C491408:Socs2 protein, rat; C015423:peoniflorin; D006027:Glycosides
Cognitive dysfunction; Diabetes; Paeoniflorin; SOCS2/IRS-1; Tau phosphorylation