Department of Research, Beijing Rehabilitation Hospital Affiliated to Capital Medical University, Beijing 100144, China; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China; School of Pharmacy, Henan University, Kaifeng, 475004, China.
Behav Brain Res. 2024 Aug 5;471:115142. doi: 10.1016/j.bbr.2024.115142. Epub 2024 Jul 6.
Depression is a life-threatening neurodegenerative disease lacking a complete cure. Cajaninstilbene acid (CSA), a potent stilbene compound, has demonstrated neuroprotective effects, however, studies on its antidepressant mechanisms are still scarce. This study examined the effects of CSA on lipopolysaccharide (LPS)-induced and chronic unpredictable mild stress (CUMS)-induced depression in mice, investigating its mechanisms related to inflammation and autophagy. Mice were treated with CSA (7.5, 15, and 30 mg/kg) daily for 3 weeks before intraperitoneal LPS injection (0.8 mg/kg). Another cohort underwent the same doses of CSA (7.5-30 mg/kg) daily for 6 weeks in accompany with CUMS stimulation. Behavioral assessments were conducted, and cortical samples were collected for molecular analysis. Findings indicate that CSA ameliorated depressive behaviors induced by both LPS and CUMS. Notably, CSA (15 mg/kg) reversed despair behavior in mice more persistently than amitriptyline, indicating that optimal doses of CSA may effectively decelerate the procession of mood despair and yield a good compliance. CSA countered CUMS-induced activation of TLR4/NF-κB pathway and the reduction in autophagy levels. Furthermore, CSA attenuated the CUMS-induced decline in neuroplasticity. Collectively, these findings suggest that CSA mitigates depression-like behaviors in mice by inhibiting TLR4/NF-κB-mediated neuroinflammation and enhancing autophagy. This research provides further insights into CSA's mechanisms of action in ameliorating depressive behaviors, offering a scientific foundation for developing CSA-based antidepressants.
抑郁症是一种危及生命的神经退行性疾病，目前尚无完全治愈的方法。大豆素（CSA）是一种有效的芪类化合物，具有神经保护作用，但关于其抗抑郁机制的研究仍然很少。本研究探讨了 CSA 对脂多糖（LPS）诱导和慢性不可预测轻度应激（CUMS）诱导的小鼠抑郁的影响，研究了其与炎症和自噬相关的机制。小鼠在腹腔注射 LPS（0.8mg/kg）前连续 3 周每天给予 CSA（7.5、15 和 30mg/kg）治疗。另一组小鼠在 CUMS 刺激的同时每天接受相同剂量的 CSA（7.5-30mg/kg）治疗 6 周。进行行为评估，并采集皮质样本进行分子分析。结果表明，CSA 改善了 LPS 和 CUMS 诱导的抑郁行为。值得注意的是，CSA（15mg/kg）比阿米替林更持久地逆转了小鼠的绝望行为，表明 CSA 的最佳剂量可能有效减缓情绪绝望的进程并产生良好的顺应性。CSA 拮抗了 CUMS 诱导的 TLR4/NF-κB 通路的激活和自噬水平的降低。此外，CSA 减轻了 CUMS 诱导的神经可塑性下降。综上所述，这些发现表明 CSA 通过抑制 TLR4/NF-κB 介导的神经炎症和增强自噬来减轻小鼠的抑郁样行为。这项研究为 CSA 改善抑郁行为的作用机制提供了进一步的认识，为开发基于 CSA 的抗抑郁药提供了科学依据。
Psychopharmacology (Berl). 2019-3-7
Fitoterapia. 2019-12-11
Zotero 插件