Inhibitory effect of berberine on morphine tolerance and hyperalgesia in mice  

作　　者：HAN Shuai MAO Hua JIN Tingting YAN Rubing WANG Ziyi ZHANG Jie SHI Jianwen LIANG Yongxin 

机构地区：[1]Department of Anesthesiology,Women’s and Children’s Hospital Affiliated to Qingdao University,Qingdao 266034,China [2]Yangzhou University,Yangzhou 225009,China [3]Qingdao University,Qingdao 266071,China [4]Department of Anesthesiology,the Affiliated Hospital of Qingdao University,Qingdao 266075,China

出　　处：《Journal of Traditional Chinese Medicine》2023年第5期915-924,共10页中医杂志（英文版）

基　　金：Natural Science Foundation of Shandong Province:Mechanism of the Compound Huanglian Decoction Against Morphine Tolerance Based on Network Pharmacology and Microglia M1/M2 Pattern(No.ZR2023MH270)。

摘　　要：OBJECTIVE: To evaluate the effect of berberine on morphine analgesia, tolerance, and hyperalgesia. METHODS: Morphine-induced acute tolerance model: mice received intraperitoneal berberine at doses of 2.5, 5.0, and 10 mg/kg;30 min later, subcutaneous morphine 10 mg/kg was injected every hour for nine continuous h. Morphine 10 mg/kg alone was administered at 24 and 48 h. Morphine-induced chronic tolerance model: mice received intraperitoneal berberine 2.5, 5.0, and 10 mg/kg;30 min later, 10 mg/kg morphine was injected subcutaneously for eight consecutive days. On the ninth day, morphine 10 mg/kg was given alone. Morphineinduced established tolerance model: mice were injected subcutaneously with morphine 10 mg/kg once a day for eight consecutive days. Berberine 2.5 mg/kg was administered on day one, four, and seven and morphine 10 mg/kg alone on day nine. The baseline latency(T0) and post-treatment latency(T1) were determined by the hot plate test, and the maximum possible analgesic effect (MPAE) was calculated. Nitric oxide synthase(NOS) activity and nitric oxide(NO) content in the spinal cord were measured by spectrophotometer. Verification of berberine analgesic effect by blocking N-methyl-Daspartate(NMDA) receptor: HT-22 and HEK-293 cells transfected with NMDA plasmid were randomly divided into five groups: control group, NMDA group, berberine low-dose, medium-dose, and high-dose groups(5, 10, 20 μmol/L, respectively). Except for the control group, cells were treated with NMDA(HT-22 cells: 20 mmol/L;HEK-293 cells: 50 μmol/L). After 24 h, cell viability was detected by cell counting kit-8. The molecular mechanism between berberine and the NMDA receptor was studied by molecular docking. RESULTS: Berberine 2.5 and 5.0 mg/kg could prolong the analgesic time of morphine. In acute and chronic morphine tolerance models, berberine could inhibit the decrease of MPAE and baseline latency(P < 0.05). In the established tolerance model, berberine could rapidly reverse the decreased MPAE(P < 0.05). The combination of berber

关 键 词：BERBERINE MORPHINE PAIN drug tolerance HYPERALGESIA 

分 类 号：R285.5[医药卫生—中药学]