Antidepressant-like effects of water extract of Cordyceps militaris (Linn.) Link by modulation of ROCK2/PTEN/Akt signaling in an unpredictable chronic mild stress-induced animal model

Yu-En Lin; Yi-Chun Chen; Kuan-Hung Lu; Yun-Ju Huang; Suraphan Panyod; Wei-Ting, Liu; Shi-Hui Yang; Yun-Sheng Lu; Mei-Hsing Chen; Lee-Yan Sheen

doi:10.1016/j.jep.2021.114194

Antidepressant-like effects of water extract of Cordyceps militaris (Linn.) Link by modulation of ROCK2/PTEN/Akt signaling in an unpredictable chronic mild stress-induced animal model

Journal

Journal of Ethnopharmacology

Journal Volume

276

Journal Issue

114194

Date Issued

2021-08

Author(s)

Yu-En Lin

Yi-Chun Chen

Kuan-Hung Lu

Yun-Ju Huang

Suraphan Panyod

Wei-Ting, Liu

Shi-Hui Yang

Yun-Sheng Lu

Mei-Hsing Chen

Lee-Yan Sheen

DOI

10.1016/j.jep.2021.114194

URI

https://www.sciencedirect.com/science/article/pii/S0378874121004219?via%3Dihub

https://scholars.tari.gov.tw/handle/123456789/15962

Abstract

Ethnopharmacology relevance: Cordyceps militaris (Linn.) Link (CM) is a medicinal mushroom traditionally used in tonics for treating several neurological disorders, including epilepsy and anxiety, in Asia. Reports have shown that CM has anti-inflammatory and anti-oxidative effects and may be beneficial for depression management. Aim of the study: This study aimed to investigate the potential of CM as an antidepressant for a long-term unpredictable chronic mild stress (UCMS) rodent models and explore its underlying mechanisms. Materials and methods: Rats were orally administered with 125 (low, L), 250 (medium, M), and 500 (high, H) mg/ kg bodyweight (bw) of the water extract of CM (WCM) for 35 consecutive days in the UCMS protocol. The levels of cerebral serotonin (5-HT), dopamine (DA), and metabolites in the frontal cortex of the rats were measured. Blood was collected to investigate the levels of proinflammatory cytokines, and the brain was dissected to assay the stress-associated ROCK2/PTEN/Akt signaling. Results: All doses of the WCM prevented abnormal behaviors induced by UCMS, including anhedonia and hypoactivity. The LWCM treatment reduced the turnover rate of 5-HT, and all doses of the WCM reduced the turnover rate of DA in the frontal cortex. The LWCM also attenuated the elevation of serum IL-1 beta induced by chronic stress. All doses of the WCM attenuated the ROCK2 protein hyperactivation, and the LWCM further increased the down-regulation of p-Akt/Akt signaling. Conclusion: The WCM has antidepressant-like effects, which may result from the regulation of the stress-related ROCK2/PTEN/Akt pathway. Therefore, the WCM may be developed and used for the complementary treatment of depression.

Subjects

Cordyceps militaris

Depression

Unpredictable chronic mild stress

Neurodegeneration

ROCK2

PTEN

Akt pathway

Publisher

Elsevier

Type

journal article