| 2021 | Reproductive Effects of Nicotinamide on Testicular Function and Structure in Old Male Rats: Oxidative, Apoptotic, Hormonal, and Morphological Analyses. | Reprod Sci | Aging is a natural process in which morphological and functional abnormalities in living organisms increase irreversibly. Nicotinamide (NAM) acts both as a precursor of many metabolites and as a cofactor of many enzymes involved in cell energy metabolism, homeostasis of redox balance, and regulation of signaling pathways. In this study, we investigated the effects of NAM treatment on morphological and biochemical changes in testis of old rats. The rats were treated with 200, 400, and 800 mg/kg NAM doses as a gavage for 1 month. As a result, we determined the dose-dependent therapeutic effects of NAM on testicular tissues of aged rats. We found that NAM treatment decreased total oxidant status (TOS), caspase 3 (CASP3) and cytochrome c (CYC) levels and increased total antioxidant status (TAS), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels (P<0.05). NAM treatment significantly reduced the age-related histopathological parameters such as cellular loss, necrotic tissue, interstitial edema, tubular damage, and vascular congestion in aged rat testicular tissue compared to the control group. Moreover, based on histomorphological analysis, we detected that NAM treatment resulted in a dose-dependent improvement in testicular tissue damage of old rats. Consequently, the results showed that the reproductive decline caused by aging could be ameliorated with NAM treatment. |
| 2021 | A Network Pharmacology-Based Analysis of the Protective Mechanism of Miao Medicine Xuemaitong Capsule Against Secondary Brain Damage in the Ischemic Area Surrounding Intracerebral Hemorrhage. | J Pharmacol Exp Ther | Intracerebral hemorrhage (ICH) is a devastating disease with the high mortality. The poor outcome of ICH is partially due to a combination of various secondary insults, including in the ischemic area. Xuemaitong capsule (XMT), a kind of traditional Chinese medicine, has been applied to clinic practice. The purpose of this study is to explore the mechanism of XMT in alleviating secondary damage in the ischemic area after ICH. We screened XMT target, compound components, and ICH-related targets using network pharmacology, cluster analysis, and enrichment analysis. We found that the tumor necrosis factor (TNF) signaling pathway might be the key signaling pathway for XMT treatment of ICH. An ICH rat model was established, as demonstrated by poor neurologic score. In the ICH rats, Western blot analysis and immunofluorescence indicated the upregulated expression of TNF receptor 1 (TNFR1), mitogen-activated protein kinase (MAPK), nuclear factor-B (NF-B), and caspase-3 (CASP3). Importantly, administration of XMT alleviated inflammation, edema, and increased perfusion in the ischemic area, whereas the expression of TNFR1, MAPK, NF-B, and CASP3 was decreased. Furthermore, Fluoro-Jade B and terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling staining revealed that XMT application also inhibited apoptosis and degradation of ischemic area neurons. In conclusion, this evidence elucidates that XMT alleviates neuron apoptosis, ischemic area inflammation, edema, and perfusion through the TNFR1-mediated CASP3/NF-B/MAPK axis. SIGNIFICANCE STATEMENT: Tumor necrosis factor (TNF) is the key signaling pathway of Xuemaitong (XMT) to intervention during intracerebral hemorrhage. Fourteen key targets [intercellular adhesion molecule 1, interleukin (IL) 6, TNF, C-C motif chemokine ligand 2, prostaglandin-endoperoxide synthase 2, v-rel reticuloendotheliosis viral oncogene homolog A, matrix metalloproteinase 9, endothelin-1 (EDN1), mitogen-activated protein kinase (MAPK) 1, fos proto-oncogene protein, caspase-3 (CASP3), jun proto-oncogene, IL1B, MAPK8] are retrieved from the data base. XMT can inhibit neuron apoptosis in the ischemic area via regulating TNF receptor 1 (TNFR1)/CASP3. XMT alleviates inflammation and edema through regulating TNFR1/nuclear factor-B and TNFR1/MAPK signaling pathways. XMT alleviates hypoperfusion in the cerebral ischemic area through mediating TNFR1/MAPK/EDN1. |
| 2021 | Developmental toxicity of Clerodendrum cyrtophyllum turcz ethanol extract in zebrafish embryo. | J Ethnopharmacol | Clerodendrum cyrtophyllum Turcz has been used in traditional medicine for the treatment of various diseases. In spite of its therapeutic applications, research on its toxicity and teratogenicity is still limited.The study aimed to investigate the developmental toxicity of the ethanol extract of C. cyrtophyllum (EE) in zebrafish embryo model.Major compounds from crude ethanol extract of Clerodendron cyrtophyllum Turcz leaves were determined using HPLC-DAD-Orbitrap-MS analysis. The developmental toxicity of EE were investigated using zebrafish embryo model. Zebrafish embryos at 6 h post-fertilization (hpf) were treated with EE at different concentrations. Egg coagulation, mortality, hatching, yolk sac edema, pericardial edema and teratogenicity were recorded each day for during a 5-day exposure. At time point 120 hpf, body length, pericardial area, heartbeat and yolk sac area were assessed. In order to elucidate molecular mechanisms for the developmental toxicity of EE, we further evaluated the effects of the EE on the expression of genes involved on signaling pathways affecting fish embryo's development such as heart development (gata5, myl7, myh6, has2, hand2, nkx 2.5), oxidative stress (cat, sod1, gpx4, gstp2), wnt pathway (β-catenin, wnt3a, wnt5, wnt8a, wnt11), or cell apoptosis (p53, bax, bcl2, casp3, casp8, casp9, apaf-1, gadd45bb) using qRT-PCR analysis.Our results demonstrated that three major components including acteoside, cirsilineol and cirsilineol-4'-O-β-D-glucopyranoside were identified from EE. EE exposure during 6-96 h post-fertilization (hpf) at doses ranging from 80 to 200 μg/mL increased embryo mortality and reduced hatching rate. EE exposure at 20 and 40 μg/mL until 72-120 hpf induced a series of malformations, including yolk sac edema, pericardial edema, spine deformation, shorter body length. Based on two prediction models using a teratogenic index (TI), a 25% lethality concentration (LD25) and the no observed-adverse-effect level (NOAEL), EE is considered as teratogenic for zebrafish embryos with TI (LC50/EC50) and LD25/NOAEC values at 96 hpf reaching 3.87 and 15.73 respectively. The mRNA expression levels of p53, casp8, bax/bcl2, gstp2, nkx2.5, wnt3a, wnt11, gadd45bb and gata5 were significantly upregulated by EE exposure at 20 and 40 μg/mL while the expression of wnt5, hand2 and bcl2 were downregulated.These results provide evidence for toxicity effects of EE to embryo stages and provide an insight into the potential toxicity mechanisms on embryonic development. |