Dataset Information

Monotropein alleviates H2O2?induced inflammation, oxidative stress and apoptosis via NF??B/AP?1 signaling.

ABSTRACT: Aging is a major risk factor in cardiovascular disease (CVD). Oxidative stress and inflammation are involved in the pathogenesis of CVD, and are closely associated with senescent vascular endothelial cells. Monotropein (Mtp) exerts various bioactive roles, including anti?inflammatory and antioxidative effects. The aim of the present study was to investigate the function of Mtp in senescent endothelial cells. An MTT assay was performed to evaluate the influence of Mtp on H2O2?stimulated human umbilical vein endothelial cells (HUVECs). Senescent cells were assessed by determining the expression of senescence?associated ??galactosidase, high mobility group AT?hook 1 and DNA damage marker ??H2A.X variant histone. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH?Px) and proinflammatory cytokine concentrations were estimated using assay kits to evaluate the levels of oxidative stress and inflammation in HUVECs. The TUNEL assay was performed to identify apoptotic cells. Furthermore, the expression levels of endothelial cell adhesion factors, NF??B, activator protein?1 (AP?1) and apoptotic proteins were determined via western blotting. Mtp enhanced HUVEC viability following H2O2 stimulation. H2O2?mediated increases in MDA, proinflammatory cytokine and endothelial cell adhesion factor levels were decreased by Mtp treatment, whereas Mtp reversed H2O2?mediated downregulation of SOD and GSH?Px activity. Furthermore, Mtp inhibited cell apoptosis, NF??B activation and AP?1 expression in H2O2?stimulated HUVECs; however, NF??B activator counteracted the anti?inflammatory, antioxidative and antiapoptotic effects of Mtp. The present study indicated that Mtp ameliorated H2O2?induced inflammation and oxidative stress potentially by regulating NF??B/AP?1.

SUBMITTER: Jiang F

PROVIDER: S-EPMC7646929 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Monotropein alleviates H2O2‑induced inflammation, oxidative stress and apoptosis via NF‑κB/AP‑1 signaling.

Jiang Feng F Xu Xiao-Rong XR Li Wei-Ming WM Xia Kun K Wang Le-Feng LF Yang Xin-Chun XC

Molecular medicine reports 20200929 6

Aging is a major risk factor in cardiovascular disease (CVD). Oxidative stress and inflammation are involved in the pathogenesis of CVD, and are closely associated with senescent vascular endothelial cells. Monotropein (Mtp) exerts various bioactive roles, including anti‑inflammatory and antioxidative effects. The aim of the present study was to investigate the function of Mtp in senescent endothelial cells. An MTT assay was performed to evaluate the influence of Mtp on H2O2‑stimulated human umb ...[more]

PMID: 33173962

Similar Datasets

Project description:As part of our continuous effort to find potential anti-inflammatory agents from endophytic fungi, a Fusarium solani strain, isolated from the plant Aponogeton undulatus Roxb., was investigated. Cerevisterol (CRVS) was identified from endophytic fungi, a Fusarium solani strain, and moreover exhibited anti-inflammatory activity. However, the underlying mode of action remains poorly understood. The aim of this study is to reveal the potential mechanisms of CRVS against inflammation on a molecular level in LPS-activated RAW 264.7 peritoneal macrophage cells. CRVS was isolated from F. solani and characterized based on spectral data analysis. The MTT assay was performed to measure cell viability in CRVS-treated macrophages. Anti-inflammatory activity was assessed by measurement of nitric oxide (NO) and prostaglandin E2 (PGE2) levels, as well as the production of various cytokines, such as tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), and -6 (IL-6) in LPS-stimulated macrophages. RT-PCR and immunoblotting analyses were done to examine the expression of various inflammatory response genes. A reporter gene assay was conducted to measure the level of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) and activator protein-1 (AP-1) transactivation. CRVS suppresses the LPS-induced production of NO and PGE2, which is a plausible mechanism for this effect is by reducing the expression of iNOS and COX-2. CRVS also decreases the expression of pro-inflammatory cytokines, such as TNF-?, IL-6, and IL-1?. CRVS halted the nuclear translocation of NF-?B by blocking the phosphorylation of inhibitory protein ?B? (I?B?) and suppressing NF-?B transactivation. The mitogen-activated protein kinases (MAPK) signaling pathways are also suppressed. CRVS treatment also inhibited the transactivation of AP-1 and the phosphorylation of c-Fos. Furthermore, CRVS could induce the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) by down-regulating Kelch-like ECH-associated protein 1 (Keap-1) and up-regulating hemeoxygenases-1 (HO-1) expression. The results suggest that CRVS acts as a natural agent for treating inflammatory diseases by targeting an MAPK, NF-?B, AP-1, and Nrf2-mediated HO-1 signaling cascade.

Project description:BackgroundAucubin (Au), an iridoid glycoside from natural plants, has antioxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in an H2O2-induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model.MethodsIn vitro experiments, the various concentrations of Au (50??g/ml, 100??g/ml, or 200??g/ml) were added in culture medium at 0?h and 6?h after neurons stimulated by H2O2 (100??M). After exposed for 12?h, neurons were collected for western blot (WB), immunofluorescence, and M29,79-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In vivo experiments, Au (20?mg/kg or 40?mg/kg) was administrated intraperitoneally at 30?min, 12?h, 24?h, and 48?h after modeling. Brain water content, neurological deficits, and cognitive functions were measured at specific time, respectively. Cortical tissue around focal trauma was collected for WB, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry, and enzyme linked immunosorbent assay (ELISA) at 72?h after TBI. RNA interference experiments were performed to determine the effects of nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with Au (40?mg/kg) treatment. Mice were intracerebroventricularly administrated with lentivirus at 72?h before TBI establishment. The cortex was obtained at 72?h after TBI and used for WB and q-PCR.ResultsAu enhanced the translocation of Nrf2 into the nucleus, activated antioxidant enzymes, suppressed excessive generation of reactive oxygen species (ROS), and reduced cell apoptosis both in vitro and vivo experiments. In the mice model of TBI, Au markedly attenuated brain edema, histological damages, and improved neurological and cognitive deficits. Au significantly suppressed high mobility group box 1 (HMGB1)-mediated aseptic inflammation. Nrf2 knockdown in TBI mice blunted the antioxidant and anti-inflammatory neuroprotective effects of the Au.ConclusionsTaken together, our data suggest that Au provides a neuroprotective effect in TBI mice model by inhibiting oxidative stress and inflammatory responses; the mechanisms involve triggering Nrf2-induced antioxidant system.

Project description:BACKGROUND:Monotropein, astragalin, and spiraeoside (MAS) are active compounds extracted from medicinal herbs; monotropein from Morinda officinalis How (Rubiaceae), astragalin (kaempferol 3-O-glucoside) from Cuscuta chinensis Lamark (Convolvulaceae) and spiraeoside from the outer scales of Allium cepa L. (Liliceae) in a ratio of 6.69:0.41:3.61. Monotropein, astragalin, and spiraeoside are well-known antioxidants, anti-inflammatory, and antinociceptive agents. The current investigation aims to study the molecular mechanism of varicocele-induced male infertility and the underlying pharmacological mechanisms of MAS. METHODS:Four groups were included: control (CTR), MAS 200 group (MAS 200?mg/kg), varicocele group (VC), and VC?+?MAS 200 group (MAS 200?mg/kg). Sprague-Dawley (SD) rats were treated with 200?mg/kg MAS or vehicle once daily for 28?days. The possible signaling mechanism and effects of MAS were measured via histological staining, immunohistochemistry, western blot, and biochemical assays. RESULTS:Parameters such as sperm motility and count, Johnsen's scores, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and expression of the steroidogenic acute regulatory protein (StAR) improved significantly in the VC?+?MAS 200 group compared with the VC group. MAS treatment of varicocele-induced group significantly decreased the levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as testicular interleukin-6 (IL6), tumor necrosis factor-? (TNF-?), ROS/RNS, and malondialdehyde (MDA). It also decreased the apoptotic index and reduced the expression of endoplasmic reticulum (ER) protein levels (Grp78, p-IRE1?, and p-JNK) and apoptotic markers such as cleaved caspase-3 and Bax/Bcl2 ratio. CONCLUSION:This study suggests that the crosstalk between oxidative stress, ER stress, and mitochondrial pathway mediates varicocele-induced testicular germ cell apoptosis. MAS promotes spermatogenesis in varicocele-induced SD rat, probably by decreasing cytokines (IL-6, TNF-?) levels, regulating abnormal sex hormones, and decreasing oxidative stress, ER stress, and apoptosis.

Dataset Information

Monotropein alleviates H2O2?induced inflammation, oxidative stress and apoptosis via NF??B/AP?1 signaling.

Publications

Monotropein alleviates H2O2‑induced inflammation, oxidative stress and apoptosis via NF‑κB/AP‑1 signaling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets