Yang Genmeng, Li Juan, Peng Yanxia, Shen Baoyu, Li Yuanyuan, Liu Liu, Wang Chan, Xu Yue, Lin Shucheng, Zhang Shuwei, Tan Yi, Zhang Huijie, Zeng Xiaofeng, Li Qi, Lu Gang
NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, Yunnan Province, China.
School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan Province, China.
J Ginseng Res. 2022 May;46(3):426-434. doi: 10.1016/j.jgr.2021.07.005. Epub 2021 Jul 14.
This study investigates the effects of ginsenoside Rb1 (GsRb1) on methamphetamine (METH)-induced toxicity in SH-SY5Y neuroblastoma cells and METH-induced conditioned place preference (CPP) in adult Sprague-Dawley rats. It also examines whether GsRb1 can regulate these effects through the NR2B/ERK/CREB/BDNF signaling pathways.
SH-SY5Y cells were pretreated with GsRb1 (20 μM and 40 μM) for 1 h, followed by METH treatment (2 mM) for 24 h. Rats were treated with METH (2 mg/kg) or saline on alternating days for 10 days to allow CPP to be examined. GsRb1 (5, 10, and 20 mg/kg) was injected intraperitoneally 1 h before METH or saline. Western blot was used to examine the protein expression of NR2B, ERK, P-ERK, CREB, P-CREB, and BDNF in the SH-SY5Y cells and the rats' hippocampus, nucleus accumbens (NAc), and prefrontal cortex (PFC).
METH dose-dependently reduced the viability of SH-SY5Y cells. Pretreatment of cells with 40 μM of GsRb1 increased cell viability and reduced the expression of METH-induced NR2B, p-ERK, p-CREB and BDNF. GsRb1 also attenuated the expression of METH CPP in a dose-dependent manner in rats. Further, GsRb1 dose-dependently reduced the expression of METH-induced NR2B, p-ERK, p-CREB, and BDNF in the PFC, hippocampus, and NAc of rats.
GsRb1 regulated METH-induced neurotoxicity and METH-induced CPP through the NR2B/ERK/CREB/BDNF regulatory pathway. GsRb1 could be a therapeutic target for treating METH-induced neurotoxicity or METH addiction.
本研究调查人参皂苷Rb1（GsRb1）对甲基苯丙胺（METH）诱导的SH-SY5Y神经母细胞瘤细胞毒性以及对成年Sprague-Dawley大鼠METH诱导的条件性位置偏爱（CPP）的影响。同时研究GsRb1是否能通过NR2B/ERK/CREB/BDNF信号通路调节这些作用。
用GsRb1（20μM和40μM）预处理SH-SY5Y细胞1小时，随后用METH（2mM）处理24小时。大鼠每隔一天接受METH（2mg/kg）或生理盐水处理，共10天，以便检测CPP。在给予METH或生理盐水前1小时腹腔注射GsRb1（5、10和20mg/kg）。采用蛋白质免疫印迹法检测SH-SY5Y细胞以及大鼠海马、伏隔核（NAc）和前额叶皮质（PFC）中NR2B、ERK、P-ERK、CREB、P-CREB和BDNF的蛋白表达。
METH剂量依赖性降低SH-SY5Y细胞活力。用40μM GsRb1预处理细胞可提高细胞活力，并降低METH诱导的NR2B、p-ERK、p-CREB和BDNF的表达。GsRb1还以剂量依赖性方式减弱大鼠中METH CPP的表达。此外，GsRb1剂量依赖性降低大鼠PFC、海马和NAc中METH诱导的NR2B、p-ERK、p-CREB和BDNF的表达。
GsRb1通过NR2B/ERK/CREB/BDNF调节通路调节METH诱导的神经毒性和METH诱导的CPP。GsRb1可能是治疗METH诱导的神经毒性或METH成瘾的治疗靶点。
