title: P2X7 as a new target for chrysophanol to treat lipopolysaccharide-induced depression in mice.
abstract: P2X7 receptor is a ligand gated ion channel found peripheral macrophages and microglia in the nervous system. The current study investigated the relationship between the activated P2X7 and depression for the first time. Chrysophanol (Chr) was examined for its protective effects against depression targeting P2X7. Chr (20mg/kg, 40mg/kg) and fluoxetine (20mg/kg) were intragastrically treated once daily for 7 consecutive days. Lipopolysaccharide (LPS, 0.5mg/kg) was intraperitoneally injected to develop depression model 30min after drug administration on day 7. Behavioral tests were measured 24h after LPS injection. Interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α levels in serum and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of P2X7/NF-κB pathway-related proteins were assessed by western blot. The findings showed that Chr remarkably reduced the elevations of IL-6, IL-1β and TNF-α caused by LPS stimulation. The expressions of P2X7, p-IKKα, p-IKKβ, p-IκBα and p-NF-κBp65 were significantly decreased by Chr pretreatment. In addition, immobility time in tail suspension test (TST) and forced swimming test (FST) were reduced by Chr without affecting spontaneous locomotor activity in open filed test (OFT) and the preference for sucrose was also recovered in sucrose preference test (SPT) with Chr preconditioning. Thus, it is reasonable to speculate that Chr might exert antidepressant effect through inhibiting P2X7/NF-κB signaling pathway.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Polymer Materials and Engineering, Nanjing Forestry University, Nanjing 210037, China.
authors.forename: Xintong
authors.initials: X
authors.lastname: You
authors.affiliation: Nanjing Hongshi Pharmaceutical Management Services Co., Ltd., Nanjing 210046, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Kong
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yichen
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Cao
authors.affiliation: Nanjing Shunan Medical Apparatus Company, Nanjing 210000, China.
authors.forename: Song
authors.initials: S
authors.lastname: Yang
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China. Electronic address: fuqiangnanjing@126.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China. Electronic address: mazhanqiangnanjing@126.com.
authors.forename: Zhangqiang
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D005518:Food Preferences / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008813:Mice, Inbred ICR; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D058486:Receptors, Purinergic P2X7; C027113:chrysophanic acid
keywords: Chrysophanol; Depression; Inflammation; P2X7