Li Ma1, Pei Hu2, Junfang Zhang3, Wugeng Cui4, Xin Zhao5. 1. Department of Neurology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei Province, China. 2. Department of Vasculocardiology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei Province, China. 3. Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, China. 4. Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, China. cuiwugeng@nbu.edu.cn. 5. Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, China. zhaoxin@nbu.edu.cn.
Abstract
RATIONALE AND OBJECTIVES: Major depression represents a significant public health problem worldwide, and effective regimen is lacking. The present study investigated the antidepressant-like effects of purpurin, a natural anthraquinone compound from Rubia tinctorum L., and explored the underlying mechanism(s). METHODS: Forced swim test (FST) and tail suspension test (TST) were used to assess antidepressant-like effects of purpurin in mice. Effects of purpurin on neuroendocrine responsivity were evaluated at the level of corticosterone and ACTH following acute restraint stress and intracerebroventricular injection of corticotrophin-releasing-factor (CRF). Serotonergic mechanisms underlying purpurin antidepressant effect were explored using biochemical, neurochemical, and pharmacological paradigms. RESULTS: Chronic purpurin treatment exerted in mice dose-dependently antidepressant-like effects on behavior and stress axis reactivity (n = 9-11 per group). The purpurin-triggered antidepressant-like effects are serotonergically dependent, since purpurin-treated mice showed escalated levels of brain serotonin and suppressed monoamine oxidase (MAO) activity (n = 8-11 per group). Consistently, chemical depletion of brain serotonin by p-chlorophenylalanine (PCPA) abolished the antidepressant-like effects of purpurin on behavior and stress axis responsivity (n = 9-10 per group). Moreover, the antidepressant effect by purpurin was preferentially counteracted by 1A-selective 5-HT receptor antagonist WAY-100635, but potentiated by 1A-selective agonist 8-OH-DPAT and sub-effective dose of serotonergic antidepressant fluoxetine (n = 9-11 per group), suggesting a crucial role for 5-HT1A related serotonergic system in mediating such purpurin antidepressant effect. CONCLUSION: We have revealed the antidepressant-like effects of purpurin on both behavior and stress axis reactivity in mice, with serotonergic system that preferentially couples with 5-HT1A receptors being critically engaged.
RATIONALE AND OBJECTIVES: Major depression represents a significant public health problem worldwide, and effective regimen is lacking. The present study investigated the antidepressant-like effects of purpurin, a natural anthraquinone compound from Rubia tinctorum L., and explored the underlying mechanism(s). METHODS: Forced swim test (FST) and tail suspension test (TST) were used to assess antidepressant-like effects of purpurin in mice. Effects of purpurin on neuroendocrine responsivity were evaluated at the level of corticosterone and ACTH following acute restraint stress and intracerebroventricular injection of corticotrophin-releasing-factor (CRF). Serotonergic mechanisms underlying purpurin antidepressant effect were explored using biochemical, neurochemical, and pharmacological paradigms. RESULTS: Chronic purpurin treatment exerted in mice dose-dependently antidepressant-like effects on behavior and stress axis reactivity (n = 9-11 per group). The purpurin-triggered antidepressant-like effects are serotonergically dependent, since purpurin-treated mice showed escalated levels of brain serotonin and suppressed monoamine oxidase (MAO) activity (n = 8-11 per group). Consistently, chemical depletion of brain serotonin by p-chlorophenylalanine (PCPA) abolished the antidepressant-like effects of purpurin on behavior and stress axis responsivity (n = 9-10 per group). Moreover, the antidepressant effect by purpurin was preferentially counteracted by 1A-selective 5-HT receptor antagonist WAY-100635, but potentiated by 1A-selective agonist 8-OH-DPAT and sub-effective dose of serotonergic antidepressant fluoxetine (n = 9-11 per group), suggesting a crucial role for 5-HT1A related serotonergic system in mediating such purpurin antidepressant effect. CONCLUSION: We have revealed the antidepressant-like effects of purpurin on both behavior and stress axis reactivity in mice, with serotonergic system that preferentially couples with 5-HT1A receptors being critically engaged.
Authors: Mendel Friedman; Alexander Xu; Rani Lee; Daniel N Nguyen; Tina A Phan; Sabrina M Hamada; Rima Panchel; Christina C Tam; Jong H Kim; Luisa W Cheng; Kirkwood M Land Journal: Molecules Date: 2020-07-07 Impact factor: 4.411
Authors: Woosuk Kim; Hyun Jung Kwon; Hyo Young Jung; Kyu Ri Hahn; Yeo Sung Yoon; In Koo Hwang; Soo Young Choi; Dae Won Kim Journal: Mol Neurobiol Date: 2022-01-30 Impact factor: 5.682