BaZiBuShen alleviates cognitive deficits and regulates Sirt6/NRF2/HO-1 and Sirt6/P53-PGC-1α-TERT signaling pathways in aging mice. (10th January 2022)

• Record Type: Journal Article
• Authors: Li, Lin; Zhang, Hao; Chen, Beibei; Xia, Bingke; Zhu, Ruyuan; Liu, Yage; Dai, Xuan; Ye, Zimengwei; Zhao, Dandan; Mo, Fangfang; Gao, Sihua; Orekhov, Alexander N.; Prentki, Marc; Wang, Lili; Guo, Shuzhen; Zhang, Dongwei
• Is Part Of: Journal of ethnopharmacology. Volume 282(2021)
• Publication Date: 2022-01-10
• Subjects: BaZiBuShen formula (BZBS) -- Aging -- Cognitive decline -- Oxidative stress -- Telomere shortening -- Immunosenescence; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2021.114653
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: BaZiBuShen formula (BZBS) is clinically used to counteract mental fatigue and to retard the aging process. Brain aging echoes in major risks of human sufferings and has become one of the main challenges to our societies and the health-care systems. Aim of the study: To investigate the effect and mode of action of BZBS on aging-associated cognitive impairments. Materials and methods: BZBS was orally administered to D-galactose and NaNO2 -induced aging mice. Premature senescence was assessed using the Morris water maze, step-down type passive avoidance, and pole-climbing tests. Telomere length was examined by qPCR analysis. Telomerase activity was assessed using PCR ELISA assay. Mitochondrial complex IV activity was examined by biochemical test. The levels of redox and immune status were determined by ELISA or biochemical assay. The expressions of sirtuin 6 (Sirt6), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), P53, telomerase reverse transcriptase (TERT), heme oxygenase-1 (HO-1), phospho(p)-nuclear factor erythroid-2 related factor 2 (NRF2), caspase-3, Bcl-2 associated x (Bax), and B-cell lymphoma-2 (Bcl-2) in the cerebral cortex were examined by Western blot and/or immunohistochemical staining. Results: BZBS intervention ameliorated reduced brain performances in aging mice, including memory, cognitive, and motor functions. In addition, BZBS administration to aging mice preserved redox homeostasis, attenuated immunosenescence, and maintained telomerase activity and telomere length. Moreover, BZBS treatment were associated with a declines in P53, caspase-3, Bax expressions and an increase in Sirt6, p–HO–1, p-NRF2, PGC-1α, and Bcl-2 expressions in the brains of this rapid aging mouse. Conclusions: BZBS attenuates premature senescence possibly via the preservation of redox homeostasis and telomere integrity, and inhibition of apoptosis in rapid aging mouse. The mechanism governing the alterations may be associated with through the activation of Sirt6/NRF2/HO-1 and Sirt6/P53-PGC-1α-TERT signaling pathways. The results suggest that BZBS may provide a novel strategy for confronting aging and age-associated diseases. Graphical abstract: Image 1 Highlights: BaZiBuShen formula (BZBS) alleviates cognitive decline in rapid aging mice. BZBS suppresses oxidative stress and immunosenecence in rapid aging mice. BZBS retards aging process through the activation of Sirt6 signaling in the brain.