BaZiBuShen alleviates altered testicular morphology and spermatogenesis and modulates Sirt6/P53 and Sirt6/NF-κB pathways in aging mice induced by D-galactose and NaNO2. (10th May 2021)

• Record Type: Journal Article
• Authors: Li, Lin; Chen, Beibei; An, Tian; Zhang, Hao; Xia, Bingke; Li, Rui; Zhu, Ruyuan; Tian, Yimiao; Wang, Lili; Zhao, Dandan; Mo, Fangfang; Li, Yu; Yang, Ge; Orekhov, Alexander N.; Prentki, Marc; Zhang, Dongwei; Jiang, Guangjian; Zhu, Xiaofeng
• Is Part Of: Journal of ethnopharmacology. Volume 271(2021)
• Publication Date: 2021-05-10
• Subjects: BaZiBuShen formula (BZBS) -- Aging -- Testes -- Spermatogenesis -- Oxidative stress -- Sirtuin 6; Neochlorogenic acid: CID 5280633 -- Chlorogenic acid: CID 1794427 -- Cryptochlorogenic acid: CID 9798666 -- Isoquercitrin: CID 5280804 -- Hyperin: CID 5281643 -- Verbascoside: CID 5281800 -- Epimedin A: CID 122197596 -- Icariin: CID 5318997 -- Baohuoside I: CID 5488822 -- Imperatorin: CID 10212 -- Osthole: CID 10228 -- Catalpol: CID 91520 -- Deoxyschizandrin: CID 43595 -- γ-Schizandrin: CID 174277; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2021.113810
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Sperm infertility and testicular atrophy are symptoms associated with aging. BaZiBuShen formula (BZBS), a patented Chinese herbal prescription composed of Semen Cuscutae, Fructus Lycii, Epimedii Folium, Fructus Schisandrae Sphenantherae, Fructus Cnidii, Fructus Rosae Laevigatae, Semen Allii Tuberosi., Radix Morindae Officinalis, Herba Cistanches, Fructus Rubi, Radix Rehmanniae Recens, Radix Cyathulae, Radix Ginseng, Cervi Cornu Pantotrichum, Hippocampus, and Fuctus Toosendan, has been used as a kidney-tonifying and anti-aging drug as well as for the treatment of impotence and male infertility in traditional Chinese medicine. Aim of the study: We aimed at investigating whether BZBS preserves sperm and testes morphology in aging mice, and to explore the underlying mechanisms. Materials and methods: BZBS was orally administered to aging mice induced by D-galactose (D-gal) and NaNO2 for 65 days. Sperm quality and testes pathophysiological alterations were examined by a Semen Analysis System, hematoxylin-eosin staining, transmission electron microscopy, and mitochondrial complex IV activity. In addition, serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-desoxyguanosine (8-OH-dG), reduced glutathione (GSH), oxidized glutathione disulfide (GSSG), testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2 ) and tumor necrosis factor-α (TNF-α) were determined by ELISA. The expressions of P450 aromatase (CYP19), sirtuin 6 (Sirt6), P53, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB)-p65, and phospho–NF–κB-p65 (NF-κB-pp65) in the testes were examined by western blot and/or immunohistochemical staining. Results: Sustained exposure to D-gal/NaNO2 caused a deterioration of sperm quality and testes morphology in this rapid aging mouse model. BZBS treatment curtailed these alterations. These beneficial effects were associated with increased serum levels of TAC, GSH/GSSG, T, E2, and FSH, and decreased levels of MDA, TNF-α, and 8-OH-dG. BZBS treatment also downregulated the expressions of P53, iNOS, and NF-κB-pp65, as well as upregulated the expressions of Sirt6 and CYP19 in aging testes. Conclusions: BZBS preserves testicular morphology and spermatogenesis possibly via inhibition of oxidative stress and the modulation of the Sirt6/P53 and Sirt6/NF-κB signaling pathways. The results shed light on the beneficial effect of BZBS on sperm quality and fertility in aging males. Graphical abstract: Image 1 Highlights: BZBS ameliorates testicular morphology and sperm quality in rapidly aging mice induced by D-galactose and NaNO2 . BZBS increases sex hormone levels in aging mice. BZBS inhibits ROS overproduction in aging mice. BZBS modulates Sirt6/P53 and Sirt6/NF-κB pathways in the testes of aging mice.