2. Academic Validation
  3. Jiawei-Xiaoyao pill elicits a rapid antidepressant effect, dependent on activating CaMKII/mTOR/BDNF signaling pathway in the hippocampus

Jiawei-Xiaoyao pill elicits a rapid antidepressant effect, dependent on activating CaMKII/mTOR/BDNF signaling pathway in the hippocampus

  • J Ethnopharmacol. 2023 Aug 9;117016. doi: 10.1016/j.jep.2023.117016.
Hailou Zhang 1,  Yan Sun 2,  Zihao Huang 1,  Zhangjie Wu 1,  Yin Ying 1,  Ruiyi Liu 1,  Juan Lin 3,  Chuyuan Li 4,  Gang Chen 5
Affiliations

Affiliations

  • 1 Interdisciplinary Institute for Personalized Medicine in Brain Disorders, Jinan University, Guangzhou, 510632, China; Departments of Psychiatry & Clinical and Translational Institute of Psychiatric Disorders, First Affiliated Hospital of Jinan University, Guangzhou, 510632, China.
  • 2 Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 3 Guangzhou Pharmaceutical Holdings Limited., Guangzhou Baiyun Mountain and Hutchison Whampoa Ltd., Guangzhou, 510515, China.
  • 4 Guangzhou Pharmaceutical Holdings Limited., Guangzhou Baiyun Mountain and Hutchison Whampoa Ltd., Guangzhou, 510515, China. Electronic address: lcy_gpc@163.com.
  • 5 Interdisciplinary Institute for Personalized Medicine in Brain Disorders, Jinan University, Guangzhou, 510632, China; Departments of Psychiatry & Clinical and Translational Institute of Psychiatric Disorders, First Affiliated Hospital of Jinan University, Guangzhou, 510632, China. Electronic address: chengang@jnu.edu.cn.
PMID: 37567427 DOI: 10.1016/j.jep.2023.117016
Abstract

Ethnopharmacological relevance: Jiawei-Xiaoyao pill (JWX), a traditional Chinese medicine, was recorded in ancient Chinese medicine pharmacopoeia using for treatment of various diseases, including mood disorders. Current mainstream antidepressants have a disadvantage in delayed onset of action. Whether JWX has rapid antidepressant potential and it underlying the mechanisms remains unclear.

Aim of the study: We aimed to assess the rapid antidepressant potential of JWX and the distinct underlying neuroplasticity signaling mechanism.

Materials and methods: The rapid antidepressant response of JWX were determined using various behavioral paradigms, and in a corticosterone (CORT)-induced depression model in mice. The molecular neuroplasticity signaling and the expression of BDNF in the hippocampus was evaluated using immunoblotting and immunostaining. The contribution of specific signaling was investigated using pharmacological interventions.

Results: A single dose of JWX induced rapid and persistent antidepressant effects in both the normal and chronic CORT-exposed mice. The phosphorylation of CaMKII, mTOR, ERK and the expressions of BDNF, synapsin1 and PSD95 increased at 30 min post JWX. JWX restored the expression of BDNF in the hippocampal dentate gyrus reduced by CORT-exposure. The rapid antidepressant effect and upregulation of BDNF expression by JWX was blunted by a mTOR antagonist, rapamycin, or a CaMKII antagonist, KN-93. CaMKII signaling blockade blunted mTOR signaling activated by JWX, but not vice versa.

Conclusion: JWX elicits a rapid antidepressant effect, via quickly stimulating CaMKII signaling, subsequently activating mTOR-BDNF signaling pathway, and thus enhancing hippocampal neuroplasticity.

Keywords

BDNF; CaMKII; Hippocampus; Jiawei-xiaoyao pill; Ketamine; Rapid antidepressant.

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