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.

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.

Traditional uses, phytochemistry and pharmacological properties of the genus Peucedanum: a review.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Peucedanum (Apiaceae) comprising more than 120 species is widely distributed in Europe, Asia and Africa. The ethnopharmacologial history of this genus indicated that some extracts of aerial and underground parts of several Peucedanum species have been used in folk medicine for treatment of various conditions, such as cough, cramps, pain, rheumatism, asthma and angina. This review focuses on ethnopharmacological uses of Peucedanum species, as well as the phytochemical, pharmacological and toxicological studies on this genus. Through this review, I intend to highlight the known and potential effects of the Peucedanum species or their isolated compounds and show which traditional medicine uses have been supported by pharmacological investigations. METHODS: Information on the Peucedanum species was collected from scientific journals, books, thesis and reports via a library and electronic search (using Google Scholar, Pubmed, Scopus, Web of Science and ScienceDirect). This review covers the available literature from 1970 to the end of September 2013. RESULTS: Although, there are about 120 species in this genus, so far many species have received no or little attention and most of pharmacological studies were performed on just about 20 species. Many phytochemical investigations on this genus confirmed that Peucedanum species are rich in essential oils and coumarins. The present review article shows that Peucedanum species have a wide spectrum of pharmacological activities and the most reported activities of Peucedanum plants come back to the presence of coumarins, flavonoids, phenolics and essential oils. CONCLUSIONS: The present review confirms that some Peucedanum species have emerged as a good source of the traditional medicine for treatment of inflammation, microbial infections, cardiopulmonary diseases and provides new insights for further investigations on isolated compounds, especially on praeruptorins, to find novel therapeutics and aid drug discovery. However, for using Peucedanum species to prevent and treat various diseases, additional pharmacological studies to find the mechanism of action, safety and efficacy of them before starting clinical trials are required.