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, Sirt3 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.

中文翻译：

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Sirtuin 3 在山奈酚的抗抑郁和抗焦虑样作用中发挥着关键作用


据估计，有 20% 的女性在更年期的某个时期会经历抑郁症。激素替代疗法（HRT）作为抑郁症和其他更年期综合症的主要疗法，会带来一些不良副作用，并可能增加癌症和心血管风险。因此，迫切需要开发治疗更年期抑郁症的新疗法。氧化应激与性激素下降相结合可能可以解释更年期特征性心理症状的发生。因此，抗氧化剂被认为是治疗衰老相关疾病（例如更年期抑郁症）的一种有前景的疗法。作为类黄酮抗氧化剂，山奈酚可能具有潜在的神经保护作用。因此，进行该研究是为了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 VCD 诱导的更年期抑郁症啮齿动物模型具有潜在的有益作用，并产生抗氧化作用，并增加海马中超氧化物歧化酶 2 (SOD2) 的脱乙酰化和 Sirtuin3 (Sirt3) 的蛋白水平。相反， Sirt3缺失会消除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补充疗法提供了一些线索。