title: Echinocystic acid reduces reserpine-induced pain/depression dyad in mice.
abstract: Chronic pain has consistently been correlated with depression. Echinocystic acid (EA), a natural triterpone enriched in various herbs and used for medicinal purpose in many Asian countries, exhibits anti-inflammatory and analgesic activities. However, little is known the effects of EA on the depression. In present study, we investigated the anti-depression activities in the mouse model of reserpine-induced pain-depression dyad. Reserpine (1 mg/kg subcutaneously daily for 3 days) caused significant depression-like behaviors and pain sensation. Subsequent treatment of EA (5 mg/kg intragastrically daily for 5 days) attenuated the reserpine-induced pain/depression dyad as shown by the increase of pain threshold and the behaviors in forced swimming test, tail suspension test, and open field test. Furthermore, treatment of EA reversed the decrease of biogenic amines (norepinephrine, dopamine, and serotonin) in the brain region of hippocampus, a structure involved in the formation of emotional disorders. Levels of serotonin receptor 5-HT1A were decreased and levels of 5-HT2A were increased in the reserpine-injected mice. Treatment of EA could restore the alterations of serotonin receptors. At the same time, the increase in GluN2B-containing NMDA receptors, p-GluA1-Ser831, PSD-95 and CaMKII were integrated with the increase in caspase-3 and iNOS levels in the hippocampus of the reserpine-injected mice. EA significantly reversed the changes of above proteins. However, EA did not affect the levels of GluN2A-containing NMDA receptors and the total levels of GluA1 and p-GluA1-Ser845. Our study provides strong evidence that EA attenuates reserpine-induced pain/depression dyad partially through regulating the biogenic amines levels and GluN2B receptors in the hippocampus.
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, 210002, China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Deng
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xin-Shang
authors.initials: XS
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China. minggao@fmmu.edu.cn.
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Zhao
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D017288:Pain Threshold / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
chemical_list: D000700:Analgesics; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D009828:Oleanolic Acid; D012110:Reserpine; C022999:echinocystic acid; D004298:Dopamine
keywords: Depression; Echinocystic acid; Hippocampus; NMDA receptor; Pain; Serotonin