Li Hao-Yuan, Wang Jing, Liang Ling-Feng, Shen Shi-Yu, Li Wei, Chen Xiao-Rong, Li Bing, Zhang Yu-Qiu, Yu Jin
Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Center Laboratories, Jinshan Hospital of Fudan University, Shanghai 201508, China.
Antioxidants (Basel). 2022 Sep 23;11(10):1886. doi: 10.3390/antiox11101886.
An estimated 20% of women experience depression at some point during menopause. Hormone replacement therapy (HRT), as the main therapy for depression and other menopausal syndromes, comes with a few undesirable side effects and a potential increase in cancer and cardiovascular risk. Consequently, there is a dire need for the development of new therapies to treat menopausal depression. Oxidative stress combined with the decline in sex hormones might explain the occurrence of psychological symptoms characteristic of menopause. Therefore, antioxidants have been suggested as a promising therapy for aging-associated diseases, such as menopausal depression. As a flavonoid antioxidant, kaempferol might have a potential neuroprotective action. Hence, the study was conducted to assess the potential antidepressant action of kaempferol and clarify the underlying mechanism. The results show that kaempferol has potential beneficial effects on VCD-induced rodent model of menopausal depression and produces antioxidant effects as well as increases the deacetylation of superoxide dismutase 2 (SOD2) and the protein level of Sirtuin3 (Sirt3) in the hippocampus. On the contrary, depletion abrogated the antidepressant- and anxiolytic-like effects as well as antioxidant effects of kaempferol. In conclusion, kaempferol might produce antidepressant effects via upregulating the expression of Sirt3, the major deacetylase in mitochondria, and subsequently activate the mitochondrial antioxidases. These findings shed some light on the use of kaempferol or vegetables and herbs that contain kaempferol as a complementary therapy for menopausal depression.
据估计，20%的女性在更年期的某个阶段会经历抑郁。激素替代疗法（HRT）作为治疗抑郁症和其他更年期综合征的主要疗法，存在一些不良副作用，并且癌症和心血管疾病风险可能会增加。因此，迫切需要开发新的疗法来治疗更年期抑郁症。氧化应激与性激素下降相结合可能解释了更年期特有的心理症状的出现。因此，抗氧化剂已被认为是治疗与衰老相关疾病（如更年期抑郁症）的一种有前景的疗法。作为一种黄酮类抗氧化剂，山奈酚可能具有潜在的神经保护作用。因此，本研究旨在评估山奈酚的潜在抗抑郁作用并阐明其潜在机制。结果表明，山奈酚对去卵巢诱导的更年期抑郁症啮齿动物模型具有潜在的有益作用，具有抗氧化作用，并增加海马中超氧化物歧化酶2（SOD2）的去乙酰化和沉默调节蛋白3（Sirt3）的蛋白水平。相反，Sirt3缺失消除了山奈酚的抗抑郁和抗焦虑样作用以及抗氧化作用。总之，山奈酚可能通过上调线粒体中的主要脱乙酰酶Sirt3的表达，进而激活线粒体抗氧化酶来产生抗抑郁作用。这些发现为使用山奈酚或含有山奈酚的蔬菜和草药作为更年期抑郁症的辅助疗法提供了一些启示。
