Improvement of neurological recovery in the insomnia rats by Warming Yang Strategy through targeting SIRT4 by inhibiting inflammation and apoptosis.

The incidence rate of insomnia is increasing, but the mechanism of it remains unclear. Warming Yang Strategy (WY) is a kind of Traditional Chinese Medicine, and it is proved to be effective in treating insomnia patients. The insomnia animal was established with chlorophenylalanine (PCPA). Morris water maze and open field test were performed to evaluate the influence of WY on the neurological recovery of insomnia rats. TUNEL staining and flow cytometry were used to measure apoptosis level. WY promoted the neurological recovery in the insomnia rats through Morris water maze and open field test evaluation. The increase of γ-aminobutyric acid, dopamine, 5-hydroxytryptamine, and norepinephrine caused by WY was suppressed by siSIRT4. The decrease of apoptosis and inflammation factors expression induced by WY was promoted by siRNA-SIRT4 (siSIRT4). WY improve neurological recovery in the insomnia rats through SIRT4 by inhibiting inflammation and apoptosis. This research might provide a novel insight for the prevention and treatment of insomnia through targeting SIRT4.

Coenzyme Q10 Supplement Rescues Postovulatory Oocyte Aging by Regulating SIRT4 Expression.

BACKGROUND: High-quality of the oocyte is crucial for embryo development and the success of human-assisted reproduction. The postovulatory aged oocytes lose developmental competence with mitochondrial dysfunction and oxidative stress. Coenzyme Q10 (CoQ10) is widely distributed in the membranes of cells and has an important role in the mitochondrial respiration chain against oxidative stress and modulation of gene expression. OBJECTIVE: The objective of this study is to investigate the functions and mechanisms of CoQ10 on delaying postovulatory oocyte aging. METHODS: Quantitative real-time PCR and Immunofluorescence staining were used to determine the expression patterns of the biogenesis genes of CoQ10 in postovulatory aged oocytes compared with fresh oocytes. The mitochondrial function, apoptosis, reactive oxygen species (ROS) accumulation and spindle abnormalities were investigated after treatment with 10 µM CoQ10 in aged groups. SIRT4 siRNA or capped RNA was injected into oocytes to investigate the function of SIRT4 on postovulatory oocyte aging and the relationship between CoQ10 and SIRT4. RESULTS: Multiple CoQ10 biosynthesis enzymes are insufficient, and a supplement of CoQ10 can improve oocyte quality and elevate the development competency of postovulatory aged oocytes. CoQ10 can attenuate the aging-induced abnormalities, including mitochondrial dysfunction, ROS accumulation, spindle abnormalities, and apoptosis in postovulatory aged oocytes. Furthermore, SIRT4, which was first found to be up-regulated in postovulatory aged oocytes, decreased following CoQ10 treatment. Finally, knockdown of SIRT4 can rescue aging-induced dysfunction of mitochondria, and the efficiency of CoQ10 rescuing dysfunction of mitochondria can be weakened by SIRT4 overexpression. CONCLUSION: Supplement of CoQ10 protects oocytes from postovulatory aging by inhibiting SIRT4 increase.