PMID- 32442588 OWN - NLM STAT- MEDLINE DCOM- 20210225 LR - 20210316 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 259 DP - 2020 Sep 15 TI - Chaihu-Longgu-Muli decoction relieves epileptic symptoms by improving autophagy in hippocampal neurons. PG - 112990 LID - S0378-8741(19)33548-2 [pii] LID - 10.1016/j.jep.2020.112990 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu-Longgu-Muli decoction (CLMD) is a well-known ancient formula in traditional Chinese medicine (TCM) to relieve disorder, clear away heat, tranquilize the mind and allay excitement. It has been used for the therapy of neuropsychiatric disorders such as epilepsy, dementia, insomnia, anxiety, and depression for several centuries in China. AIM OF THE STUDY: This paper is based on the assumption that the mechanism by which CLMD relieves epileptic symptoms in rats is associated with improving autophagy. Several experimental methods are designed to testify the hypothesis. MATERIALS AND METHODS: The lithium-pilocarpine-induced epilepsy model was established in rats. The seizure frequency was recorded. Morphology and number of autophagosomes in hippocampal dentate gyrus was detected with a transmission electron microscope (TEM). Expression of Beclin-1, microtubule-associated proteins 1A/1B light chain 3 (LC3), and mammalian target of rapamycin (mTOR) in dentate gyrus was measured by immunofluorescence assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western-blotting. RESULTS: CLMD could significantly relieve the seizure frequency and improve autophagy in hippocampal dentate gyrus. Meanwhile, the level of Beclin-1 and LC3B decreased significantly, while mTOR increased remarkably after medical intervention. CONCLUSIONS: CLMD could improve autophagy in hippocampal dentate gyrus due to epilepsy, especially at high dose. The mechanism may be related to upregulated expression of mTOR and downregulated expression of Beclin-1 and LC3B. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Yang, Ping AU - Yang P AD - Department of Psychiatry, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, NO.427, Middle Furong Road, Changsha, Hunan Province, 410007, China; Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, NO.300, Xueshi Road, Changsha, Hunan Province, 410208, China. FAU - Qin, You AU - Qin Y AD - Institute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, NO. 8, Yuehua Road, Changsha, Hunan Province, 410013, China. FAU - Zhu, Yong AU - Zhu Y AD - Department of Psychiatry, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, NO.427, Middle Furong Road, Changsha, Hunan Province, 410007, China. FAU - Li, Feng AU - Li F AD - Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, NO.300, Xueshi Road, Changsha, Hunan Province, 410208, China; School of Dentistry, University of California Los Angeles, 405 Hilgard Ave, Los Angeles, CA, 90095, USA. FAU - Xia, Shuai-Shuai AU - Xia SS AD - Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, NO.300, Xueshi Road, Changsha, Hunan Province, 410208, China. FAU - Zhou, Bin AU - Zhou B AD - Department of Psychiatry, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, NO.427, Middle Furong Road, Changsha, Hunan Province, 410007, China. FAU - Wang, Qin AU - Wang Q AD - Department of Psychiatry, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, NO.427, Middle Furong Road, Changsha, Hunan Province, 410007, China. FAU - Lu, Jun AU - Lu J AD - Department of Psychiatry, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, NO.427, Middle Furong Road, Changsha, Hunan Province, 410007, China. FAU - Li, Liang AU - Li L AD - Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, NO.300, Xueshi Road, Changsha, Hunan Province, 410208, China. Electronic address: liliang@hnucm.edu.cn. FAU - Huang, Hui-Yong AU - Huang HY AD - Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, NO.300, Xueshi Road, Changsha, Hunan Province, 410208, China. Electronic address: huanghy@hnucm.edu.cn. LA - eng PT - Journal Article DEP - 20200519 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anticonvulsants) RN - 0 (Autophagy-Related Proteins) RN - 0 (Drugs, Chinese Herbal) RN - 0 (chaihu-longgu-muli decoction) RN - 01MI4Q9DI3 (Pilocarpine) RN - G4962QA067 (Lithium Chloride) SB - IM MH - Animals MH - Anticonvulsants/*pharmacology MH - Autophagosomes/drug effects/metabolism/ultrastructure MH - Autophagy/*drug effects MH - Autophagy-Related Proteins/genetics/metabolism MH - Behavior, Animal/drug effects MH - Disease Models, Animal MH - Drugs, Chinese Herbal/*pharmacology MH - Epilepsy/chemically induced/*drug therapy/metabolism/pathology MH - Hippocampus/*drug effects/metabolism/physiopathology/ultrastructure MH - Lithium Chloride MH - Male MH - Neurons/*drug effects/metabolism/pathology MH - Pilocarpine MH - Rats, Sprague-Dawley MH - Signal Transduction OTO - NOTNLM OT - Autophagy OT - Chaihu-Longgu-Muli decoction (CLMD) OT - Epilepsy OT - Hippocampus OT - Status epilepticus COIS- Declaration of competing interest The authors declare that there are no conflicts of interest regarding the publication of this article. EDAT- 2020/05/23 06:00 MHDA- 2021/02/26 06:00 CRDT- 2020/05/23 06:00 PHST- 2019/09/08 00:00 [received] PHST- 2020/05/05 00:00 [revised] PHST- 2020/05/16 00:00 [accepted] PHST- 2020/05/23 06:00 [pubmed] PHST- 2021/02/26 06:00 [medline] PHST- 2020/05/23 06:00 [entrez] AID - S0378-8741(19)33548-2 [pii] AID - 10.1016/j.jep.2020.112990 [doi] PST - ppublish SO - J Ethnopharmacol. 2020 Sep 15;259:112990. doi: 10.1016/j.jep.2020.112990. Epub 2020 May 19.