PMID- 30694908 OWN - NLM STAT- MEDLINE DCOM- 20191129 LR - 20211204 IS - 1473-558X (Electronic) IS - 0959-4965 (Print) IS - 0959-4965 (Linking) VI - 30 IP - 4 DP - 2019 Mar 6 TI - Leonurine promotes neurite outgrowth and neurotrophic activity by modulating the GR/SGK1 signaling pathway in cultured PC12 cells. PG - 247-254 LID - 10.1097/WNR.0000000000001180 [doi] AB - Depression is a common psychiatric disorder that affects almost 10% of children and adolescents worldwide. Numerous synthetic chemical antidepressants used to treat depression have adverse side effects. Therefore, new therapeutic approaches for depression treatment are urgently needed. Leonurus cardiaca has recently been shown to be effective for the treatment of nervous system diseases such as depression, but its mechanism is not clear. In this study, we aimed to reveal the mechanism underlying leonurine's antidepressant activity. Leonurine was used to treat corticosterone-induced PC12 cells to examine its effect on neurite outgrowth and neurotrophic factors after treatment with the inhibitor of glucocorticoid receptor (GR) and serum-inducible and glucocorticoid-inducible kinase 1 (SGK1). Methyl thiazolyl tetrazolium assays were used to evaluate the viability of cells. High content analysis was used to detect cell area, total neurite length, maximum neurite length, and expression of GR, SGK1, brain-derived neurotrophic factor (BDNF), neurotrophic factor-3 (NT-3), and B-cell lymphoma-2 (BCL-2). The results showed that leonurine increased cell viability in a concentration-dependent manner, with the maximal prosurvival effect at 60 muM. Leonurine increased cell area, total neurite length, and maximum neurite length of corticosterone-induced PC12 cells, increased the expression of GR, BDNF, NT-3, and BCL-2, and decreased the expression of SGK1. After treatment with GR inhibitor RU486, the expressions of GR, BDNF, NT-3, and BCL-2 were significantly decreased and SGK1 was increased. In contrast, treatment with GSK650394 had the opposite effect of RU486. Our data indicate that leonurine promotes neurite outgrowth and neurotrophic activity in cultured PC12 cells, and its potential mechanism may involve the GR/SGK1 signaling pathway. FAU - Meng, Pan AU - Meng P AD - Institute of Innovation and Applied Research in Chinese Medicine. FAU - Zhu, Qing AU - Zhu Q AD - Institute of Innovation and Applied Research in Chinese Medicine. AD - The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China. FAU - Yang, Hui AU - Yang H AD - The First Affiliated Hospital, Hunan University of Chinese Medicine. FAU - Liu, Dan AU - Liu D AD - The First Affiliated Hospital, Hunan University of Chinese Medicine. FAU - Lin, Xiaoyuan AU - Lin X AD - The First Affiliated Hospital, Hunan University of Chinese Medicine. FAU - Liu, Jian AU - Liu J AD - The First Affiliated Hospital, Hunan University of Chinese Medicine. FAU - Fan, Jingying AU - Fan J AD - Institute of Innovation and Applied Research in Chinese Medicine. FAU - Liu, Xiaodan AU - Liu X AD - Institute of Innovation and Applied Research in Chinese Medicine. FAU - Su, Wei AU - Su W AD - Institute of Innovation and Applied Research in Chinese Medicine. FAU - Liu, Lin AU - Liu L AD - The First Affiliated Hospital, Hunan University of Chinese Medicine. FAU - Wang, Yuhong AU - Wang Y AD - Institute of Innovation and Applied Research in Chinese Medicine. FAU - Cai, Xiong AU - Cai X AD - Institute of Innovation and Applied Research in Chinese Medicine. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Neuroreport JT - Neuroreport JID - 9100935 RN - 0 (Antidepressive Agents) RN - 0 (Immediate-Early Proteins) RN - 0 (Receptors, Glucocorticoid) RN - 09Q5W34QDA (leonurine) RN - 632XD903SP (Gallic Acid) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (serum-glucocorticoid regulated kinase) SB - IM MH - Animals MH - Antidepressive Agents/*pharmacology MH - Cell Survival/drug effects MH - Gallic Acid/*analogs & derivatives/pharmacology MH - Immediate-Early Proteins/drug effects/metabolism MH - Neuronal Outgrowth/*drug effects MH - PC12 Cells MH - Protein Serine-Threonine Kinases/drug effects/metabolism MH - Rats MH - Receptors, Glucocorticoid/drug effects/metabolism MH - Signal Transduction/*drug effects PMC - PMC6392205 EDAT- 2019/01/30 06:00 MHDA- 2019/11/30 06:00 PMCR- 2019/02/27 CRDT- 2019/01/30 06:00 PHST- 2019/01/30 06:00 [pubmed] PHST- 2019/11/30 06:00 [medline] PHST- 2019/01/30 06:00 [entrez] PHST- 2019/02/27 00:00 [pmc-release] AID - 10.1097/WNR.0000000000001180 [doi] PST - ppublish SO - Neuroreport. 2019 Mar 6;30(4):247-254. doi: 10.1097/WNR.0000000000001180.