A refined formula derived from Jiawei-Xiaoyao pill exerts rapid antidepressant-like effects in LPS-induced depression by reducing neuroinflammation and restoring neuroplasticity signaling.

Autor: Wu Z; Interdisciplinary Institute for Personalized Medicine in Brain Disorders, School of Chinese Medicine, Jinan University, Guangzhou, 510632, PR China; Zhuhai Institute of Jinan University, Zhuhai, 519070, PR China; Guangdong-Hong Kong-Macao Joint Laboratory of Traditional Chinese Medicine on Brain-Peripheral Homeostasis and Comprehensive Health, Jinan University, Guangzhou, 510632, PR China; Departments of Psychiatry & Clinical and Translational Institute of Psychiatric Disorders, First Affiliated Hospital of Jinan University, Guangzhou, 510632, PR China., Yin Y; Interdisciplinary Institute for Personalized Medicine in Brain Disorders, School of Chinese Medicine, Jinan University, Guangzhou, 510632, PR China; Zhuhai Institute of Jinan University, Zhuhai, 519070, PR China; Guangdong-Hong Kong-Macao Joint Laboratory of Traditional Chinese Medicine on Brain-Peripheral Homeostasis and Comprehensive Health, Jinan University, Guangzhou, 510632, PR China; Departments of Psychiatry & Clinical and Translational Institute of Psychiatric Disorders, First Affiliated Hospital of Jinan University, Guangzhou, 510632, PR China., Liu R; Interdisciplinary Institute for Personalized Medicine in Brain Disorders, School of Chinese Medicine, Jinan University, Guangzhou, 510632, PR China; Zhuhai Institute of Jinan University, Zhuhai, 519070, PR China; Guangdong-Hong Kong-Macao Joint Laboratory of Traditional Chinese Medicine on Brain-Peripheral Homeostasis and Comprehensive Health, Jinan University, Guangzhou, 510632, PR China; Departments of Psychiatry & Clinical and Translational Institute of Psychiatric Disorders, First Affiliated Hospital of Jinan University, Guangzhou, 510632, PR China., Li X; Interdisciplinary Institute for Personalized Medicine in Brain Disorders, School of Chinese Medicine, Jinan University, Guangzhou, 510632, PR China; Zhuhai Institute of Jinan University, Zhuhai, 519070, PR China; Guangdong-Hong Kong-Macao Joint Laboratory of Traditional Chinese Medicine on Brain-Peripheral Homeostasis and Comprehensive Health, Jinan University, Guangzhou, 510632, PR China., Sun Y; Key Laboratory of Integrative Biomedicine for Brain Diseases, School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China., Yau SY; Department of Rehabilitation Sciences, Hong Kong Polytechnic University, PR China., Wu L; Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, PR China., Liu Y; Interdisciplinary Institute for Personalized Medicine in Brain Disorders, School of Chinese Medicine, Jinan University, Guangzhou, 510632, PR China; Zhuhai Institute of Jinan University, Zhuhai, 519070, PR China., Adzic M; 'Vinča Institute' of Nuclear Sciences, Laboratory of Molecular Biology and Endocrinology 090, University of Belgrade, 11001 Belgrade, Serbia., Zhang H; Interdisciplinary Institute for Personalized Medicine in Brain Disorders, School of Chinese Medicine, Jinan University, Guangzhou, 510632, PR China; Zhuhai Institute of Jinan University, Zhuhai, 519070, PR China; Guangdong-Hong Kong-Macao Joint Laboratory of Traditional Chinese Medicine on Brain-Peripheral Homeostasis and Comprehensive Health, Jinan University, Guangzhou, 510632, PR China; Departments of Psychiatry & Clinical and Translational Institute of Psychiatric Disorders, First Affiliated Hospital of Jinan University, Guangzhou, 510632, PR China. Electronic address: hailouzhang_2021@yeah.net., Chen G; Interdisciplinary Institute for Personalized Medicine in Brain Disorders, School of Chinese Medicine, Jinan University, Guangzhou, 510632, PR China; Zhuhai Institute of Jinan University, Zhuhai, 519070, PR China; Guangdong-Hong Kong-Macao Joint Laboratory of Traditional Chinese Medicine on Brain-Peripheral Homeostasis and Comprehensive Health, Jinan University, Guangzhou, 510632, PR China; Departments of Psychiatry & Clinical and Translational Institute of Psychiatric Disorders, First Affiliated Hospital of Jinan University, Guangzhou, 510632, PR China. Electronic address: chengang@jnu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Dec 05; Vol. 335, pp. 118647. Date of Electronic Publication: 2024 Aug 02.
DOI: 10.1016/j.jep.2024.118647
Abstrakt: Ethnopharmacological Relevance: Jiawei-Xiaoyao Pill (JWX), a classic formula in traditional Chinese medicine, is derived from Xiaoyao Pill by adding significant amounts of Gardeniae Fructus (GF) and Moutan Cortex (MC). It is frequently used for the treatment of depression. JWX has been demonstrated to uniquely elicit rapid antidepressant-like effects within the prescribed dosage range. To date, GF has been shown to have rapid antidepressant-like effects, but a much higher dose is required than its proportion in JWX. It is assumed that the synergism of GF with a minimum number of other herbs in JWX serves as a refined formula that exerts these rapid antidepressant-like effects. Identification of a refined formula is important for prioritizing the herbs and ingredients to optimize the quality control of JWX. However, such a refined formula for JWX has not been identified yet.
Aim of the Study: Here we aimed to identify a refined formula derived from JWX for optimized rapid antidepressant-like effects. Since the neuroinflammation mechanism involving in depression treatment has not been previously investigated for JWX, we tested the mechanism for both JWX and the refined formula.
Materials and Methods: Individual herbs (MC; ASR, Angelica Sinensis Radix; Bupleuri Radix; Paeonia Radix Alba) that show antidepressant-like responses were mixed with GF at the proportional dosage in JWX to identify the refined formula. Rapid antidepressant-like effects were assessed by using NSF (Novelty Suppressed Feeding Test) and other behavioral tests following a single administration. The identified formula was further tested in a lipopolysaccharide (LPS)-induced depressive model, and the molecular signaling mechanisms were investigated using Western blot analysis, immunofluorescence, and pharmacological inhibition of mTOR signaling. Scopolamine (Scop) was used as a positive control for induction of rapid antidepressant effects.
Results: A combination of GF, MC and ASR (GMA) at their dosages proportional to JWX induced behavioral signs of rapid antidepressant-like responses in both normal and LPS-treated mice, with the antidepressant-like effects sustained for 5 d. Similar to JWX or Scop, GMA rapidly reduced the neuroinflammation signaling of Iba-1-NF-кB, enhanced neuroplasticity signaling of CaMKII-mTOR-BDNF, and attenuated the upregulated expressions of the NMDAR sub-units GluN1 and GluN2B in the hippocampus of LPS-treated mice. GMA, JWX and Scop rapidly restored the number of BDNF-positive cells reduced by LPS treatment in the CA3 region of the hippocampus. Furthermore, rapamycin, a selective inhibitor of mTOR, blunted the rapid antidepressant-like effects and hippocampal BDNF signaling upregulation by GMA.
Conclusion: GMA may serve as a refined formula from JWX, capable of inducing rapid antidepressant-like effects. In the LPS-induced depression model, the effects of GMA were mediated via rapidly alleviating neuroinflammation and enhancing neuroplasticity.
Competing Interests: Declaration of competing interest The authors declare there is no commercial or financial relationships that could be construed as a potential conflict of interest regarding this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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