Sirtuin 3 Plays a Critical Role in the Antidepressant- and Anxiolytic-like Effects of Kaempferol

Abstract

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.

Excessive processing and acetylation of OPA1 aggravate age‐related hearing loss via the dysregulation of mitochondrial dynamics

“…Therefore, we speculate that increased levels of OPA1 deacetylation may play a protective role in the aging process of cochlear hair cells. Here, we substantiated this hypothesis through activating SIRT3 with kaempferol (Li et al., 2022 ; Marfe et al., 2009 ), a small polyphenolic molecule widely found in plants, which has been shown in several studies to ameliorate a variety of neurodegenerative diseases including Alzheimer's disease (Holland et al., 2020 ; Xie et al., 2022 ) and cognitive impairment (Li et al., 2022 ).…”

Bioactive Lignan Honokiol Alleviates Ovarian Oxidative Stress in Aging Laying Chickens by Regulating SIRT3/AMPK Pathway

“…Notably, SIRT3, predominantly localized in mitochondria, regulates ATP levels, and loss of SIRT3 leads to reduced ATP levels in multiple organs [ 11 ]. Activation of SIRT3 is also implicated in the extension of caloric restriction lifespan by deacetylating mitochondrial proteins and activating mitochondrial superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2), thereby mitigating DNA damage caused by oxidative stress [ 38 , 39 ]. In addition, SIRT1 [ 40 ] and SIRT3 [ 41 ] can participate in a positive feedback loop with AMPK.…”

Network pharmacology analysis of a patented Chinese herbal medicine for alleviating anxiety disorder in in vitro fertilization-embryo transfer

“…Pharmacological studies have shown that quercetin and kaempferol have anxiolytic effects. 38 , 39 Quercetin is believed to have antioxidant, anti-inflammatory, immunoprotective, and anticancer effects. It was found to alleviate anxiety-like behaviour and monoamine oxidase activity in mice by regulating oxidative stress.…”