scholarly journals Protection against Doxorubicin-Related Cardiotoxicity by Jaceosidin Involves the Sirt1 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Yuzhou Liu ◽  
Liying Zhou ◽  
Binbin Du ◽  
Yuan Liu ◽  
Junhui Xing ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Biological Activities ◽  
Cardiac Injury ◽  
Cell Loss ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Injury Model ◽  
Radical Generation ◽  
Acute Cardiotoxicity

The clinical use of doxorubicin (DOX) is largely limited by its cardiotoxicity. Previous studies have shown that jaceosidin has many biological activities. However, little is known about whether jaceosidin can attenuate DOX-related acute cardiotoxicity. Here, we investigated the therapeutic effects of jaceosidin on DOX-induced acute cardiotoxicity. Mice were intraperitoneally injected with a single dose of DOX to establish an acute cardiac injury model. To explore the protective effects, mice were orally administered jaceosidin daily for 7 days, with dosing beginning 2 days before DOX injection. The results demonstrated that jaceosidin dose-dependently reduced free radical generation, inflammation accumulation, and cell loss induced by DOX in cardiomyocytes. Further studies showed that jaceosidin treatment inhibited myocardial oxidative damage and the inflammatory response and attenuated myocardial apoptotic death, thus improving cardiac function in mice injected with DOX. The inhibitory effects of jaceosidin on DOX-related acute cardiotoxicity were mediated by activation of the sirtuin1 (Sirt1) signaling pathway. Jaceosidin lost its protective effect against DOX-related injury in Sirt1-deficient cardiomyocytes and mice. In conclusion, jaceosidin has protective potential in treating DOX-related cardiac injury through activation of the Sirt1 signaling pathway.

scholarly journals Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/β-catenin pathway

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Guo Zu ◽  
Jing Guo ◽  
Ningwei Che ◽  
Tingting Zhou ◽  
Xiangwen Zhang
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Ginsenoside Rg1 ◽  
Intestinal Ischemia Reperfusion

Abstract Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients in Panax ginseng, and it attenuates inflammation and apoptosis. The aims of our study were to explore the potential of Rg1 for the treatment of intestinal I/R injury and to determine whether the protective effects of Rg1 were exerted through the Wnt/β-catenin signaling pathway. In this study, Rg1 treatment ameliorated inflammatory factors, ROS and apoptosis that were induced by intestinal I/R injury. Cell viability was increased and cell apoptosis was decreased with Rg1 pretreatment following hypoxia/reoxygenation (H/R) in the in vitro study. Rg1 activated the Wnt/β-catenin signaling pathway in both the in vivo and in vitro models, and in the in vitro study, the activation was blocked by DKK1. Our study provides evidence that pretreatment with Rg1 significantly reduces ROS and apoptosis induced by intestinal I/R injury via activation of the Wnt/β-catenin pathway. Taken together, our results suggest that Rg1 could exert its therapeutic effects on intestinal I/R injury through the Wnt/β-catenin signaling pathway and provide a novel treatment modality for intestinal I/R injury.

scholarly journals Veronicastrum axillare Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Suppression of Proinflammatory Mediators and Downregulation of the NF-κB Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Quanxin Ma ◽  
Kai Wang ◽  
Qinqin Yang ◽  
Shun Ping ◽  
Weichun Zhao ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Biological Activities ◽  
Interleukin 1 ◽  
Folk Medicine ◽  
Protective Effects ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory

Veronicastrum axillare is a traditional medical plant in China which is widely used in folk medicine due to its versatile biological activities, especially for its anti-inflammatory effects. However, the detailed mechanism underlying this action is not clear. Here, we studied the protective effects of V. axillare against acute lung injury (ALI), and we further explored the pharmacological mechanisms of this action. We found that pretreatment with V. axillare suppressed the release of proinflammatory cytokines in the serum of ALI mice. Histological analysis of lung tissue demonstrated that V. axillare inhibited LPS-induced lung injury, improved lung morphology, and reduced the activation of nuclear factor-κB (NF-κB) in the lungs. Furthermore, the anti-inflammatory actions of V. axillare were investigated in vitro. We observed that V. axillare suppressed the mRNA expression of interleukin-1β (IL-1β), IL-6, monocyte chemotactic protein-1 (MCP-1), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) in RAW264.7 cells challenged with LPS. Furthermore, pretreatment of V. axillare in vitro reduced the phosphorylation of p65 and IκB-α which is activated by LPS. In conclusion, our data firstly demonstrated that the anti-inflammatory effects of V. axillare against ALI were achieved through downregulation of the NF-κB signaling pathway, thereby reducing the production of inflammatory mediators.

scholarly journals Roles of the pyroptosis signaling pathway in a sepsis-associated encephalopathy cell model

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094976
Author(s):  
Yan Wang ◽  
Xueyan Liu ◽  
Qiang Wang ◽  
Xin Yang
Keyword(s):  
Flow Cytometry ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Cell Model ◽  
Cell Damage ◽  
Combined Treatment ◽  
Therapeutic Effects ◽  
Inhibitory Effects ◽  
Caspase Cleavage ◽  
Associated Proteins

Objectives The inhibition of pyroptosis has a protective effect in sepsis-associated encephalopathy (SAE). However, the mechanisms underlying pyroptosis in SAE remain to be elucidated. Methods Here, we investigated the effects of the caspase inhibitors, Belnacasan (Beln) and Wedelolactone (Wede), on an induced model of SAE in P12 cells, using immunofluorescence, ELISA, western blotting, and flow cytometry. Results The cell viability decreased, IL-1β and IL-18 secretion increased, and the levels of the caspase cleavage products, N-terminal gasdermin D, cleaved caspase-1, and cleaved caspase-11, increased in P12 cells following combined treatment with lipopolysaccharides (LPS) and adenosine triphosphate (ATP). However, treatment with Beln or Wede ameliorated the effects induced by LPS and ATP. Neither Beln nor Wede notably affected the levels of cell apoptosis-associated proteins but these inhibitors regulated the levels of cell pyroptosis-associated proteins. Further, the combination of Beln and Wede exerted greater inhibitory effects on cell pyroptosis than either Beln or Wede alone. Conclusions The results demonstrated that both the canonical and non-canonical signaling pathways of cell pyroptosis are involved in LPS-induced cell damage and that the non-canonical signaling pathway may be involved to a greater extent. This suggests that the inhibition of pyroptosis may exert potential therapeutic effects on SAE.

Diallyl trisulfide and diallyl disulfide ameliorate cardiac dysfunction by suppressing apoptotic and enhancing survival pathways in experimental diabetic rats

2013 ◽  
Vol 114 (3) ◽  
pp. 402-410 ◽  
Author(s):  
Yao-Te Huang ◽  
Chun-Hsu Yao ◽  
Chia-Li Way ◽  
Kung-Wei Lee ◽  
Cheng-Yen Tsai ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
Biological Activities ◽  
Akt Signaling ◽  
Diabetic Rat ◽  
Diabetic Patients ◽  
Diallyl Disulfide ◽  
Therapeutic Effects ◽  
Diallyl Trisulfide ◽  
Akt Signaling Pathway

Cardiovascular disease is one of the major causes of mortality in diabetic patients. Mounting studies have shown that garlic exhibits, possibly through its antioxidant potential, diverse biological activities. In this study, we investigated the alleviating effects of garlic oil (GO) and its two major components, diallyl disulfide (DADS) and diallyl trisulfide (DATS), on diabetic cardiomyopathy in rats. Physiological cardiac parameters were obtained using echocardiography. Apoptotic cells were evaluated using TUNEL and DAPI staining. Protein expression levels were determined using Western blotting analysis. Our findings indicated that in diabetic rat hearts significantly decreased fractional shortening percentage, increased levels of nitrotyrosine, an elevated number of TUNEL-positive cells, enhanced levels of caspase 3 expression, and decreased PI3K-Akt signaling pathway activities were observed. Furthermore, all of these alterations were reversed following both GO and DATS (or DADS) administrations through increasing PI3K-Akt signaling pathway activities and inhibiting both the death receptor-dependent and the mitochondria-dependent apoptotic pathways. In conclusion, this study shows that DATS and DADS, with the efficacy order DATS > DADS, have the therapeutic potential for ameliorating diabetic cardiomyopathy. Furthermore, the therapeutic effects of GO on diabetic cardiomyopathy should be mainly from DATS and DADS.

The protective effects of activating Sirt1/NF-κB pathway for neurological disorders

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yanhong Song ◽  
Ziyi Wu ◽  
Ping Zhao
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Nuclear Factor Κb ◽  
Vital Role ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Relevant Evidence ◽  
Almost All

Abstract Sirt1, a member of the sirtuins family, is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase. It can be involved in the regulation of several processes including inflammatory response, apoptosis, oxidative stress, energy metabolism, and autophagy by exerting deacetylation. Nuclear factor-κB (NF-κB), a crucial nuclear transcription factor with specific DNA binding sequences, exists in almost all cells and plays a vital role in several biological processes involving inflammatory response, immune response, and apoptosis. As the hub of multiple intracellular signaling pathways, the activity of NF-κB is regulated by multiple factors. Sirt1 can both directly deacetylate NF-κB and indirectly through other molecules to inhibit its activity. We would like to emphasize that Sirt1/NF-κB is a signaling pathway that is closely related to neuroinflammation. Many recent studies have demonstrated the neuroprotective effects of Sirt1/NF-κB signaling pathway activation applied to the treatment of neurological related diseases. In this review, we focus on new advances in the neuroprotective effects of the Sirt1/NF-κB pathway. First, we briefly review Sirt1 and NF-κB, two key molecules of cellular metabolism. Next, we discuss the connection between NF-κB and neuroinflammation. In addition, we explore how Sirt1 regulates NF-κB in nerve cells and relevant evidence. Finally, we analyze the therapeutic effects of the Sirt1/NF-κB pathway in several common neuroinflammation-related diseases.

scholarly journals (–)-Catechin-7-O-β-d-Apiofuranoside Inhibits Hepatic Stellate Cell Activation by Suppressing the STAT3 Signaling Pathway

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 30 ◽  
Author(s):  
Yong Joo Park ◽  
Dong Min Kim ◽  
Mi Ho Jeong ◽  
Jae Sik Yu ◽  
Hae Min So ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cell ◽  
Cell Activation ◽  
Stellate Cell ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Etoh Extract ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Hepatic fibrosis is characterized by the abnormal deposition of extracellular matrix (ECM) proteins. During hepatic fibrogenesis, hepatic stellate cell (HSC) activation followed by chronic injuries is considered a key event in fibrogenesis, and activated HSCs are known to comprise approximately 90% of ECM-producing myofibroblasts. Here, we demonstrated that (–)-catechin-7-O-β-d-apiofuranoside (C7A) significantly inhibited HSC activation via blocking the signal transducer and activator of transcription 3 (STAT3) signaling pathway. This is the first study to show the hepatic protective effects of C7A with possible mechanisms in vitro and in vivo. In our bioactivity screening, we figured out that the EtOH extract of Ulmus davidiana var. japonica root barks, which have been used as a Korean traditional medicine, inhibited collagen synthesis in HSCs. Four catechins isolated from the EtOAc fraction of the EtOH extract were compared with each other in terms of reduction in collagen, which is considered as a marker of hepatic protective effects, and C7A showed the strongest inhibitory effects on HSC activation in protein and qPCR analyses. As a possible mechanism, we investigated the effects of C7A on the STAT3 signaling pathway, which is known to activate HSCs. We found that C7A inhibited phosphorylation of STAT3 and translocation of STAT3 to nucleus. C7A also inhibited expressions of MMP-2 and MMP-9, which are downstream genes of STAT3 signaling. Anti-fibrotic effects of C7A were evaluated in a thioacetamide (TAA)-induced liver fibrosis model, which indicated that C7A significantly inhibited ECM deposition through inhibiting STAT3 signaling. C7A decreased serum levels of aspartate amino transferase and alanine transaminase, which were markedly increased by TAA injection. Moreover, ECM-associated proteins and mRNA expression were strongly suppressed by C7A. Our study provides the experimental evidence that C7A has inhibitory effects on HSC activation after live injury and has preventive and therapeutic potentials for the management of hepatic fibrosis.

Tangeretin Inhibits Oxidative Stress and Inflammation via Upregulating Nrf-2 Signaling Pathway in Collagen-Induced Arthritic Rats

Pharmacology ◽  
2019 ◽  
Vol 104 (3-4) ◽  
pp. 187-195 ◽  
Author(s):  
Xing Li ◽  
Peigen Xie ◽  
Yu Hou ◽  
Shudong Chen ◽  
Peiheng He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Chinese Herb ◽  
Biological Properties ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory

Background/Aims: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats. Methods: TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1β [IL-1β], ­IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism. Results: TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1β, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway. Conclusion: TAN might have potential as a therapeutic agent for the treatment of RA.

scholarly journals Activation of Nrf2 by miR-152 Inhibits Doxorubicin-Induced Cardiotoxicity via Attenuation of Oxidative Stress, Inflammation, and Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Wen-Bin Zhang ◽  
Xin Lai ◽  
Xu-Feng Guo
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Viral Vector ◽  
Cardiac Injury ◽  
Cell Loss ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Myocardial Apoptosis ◽  
Promising Therapeutic Target ◽  
Nrf2 Signaling Pathway

Doxorubicin (DOX) could trigger congestive heart failure, which largely limited the clinical use of DOX. microRNAs (miRNAs) were closely involved in the pathogenesis of DOX-induced cardiomyopathy. Here, we aimed to investigate the effect of miR-152 on DOX-induced cardiotoxicity in mice. To study this, we used an adeno-associated viral vector to overexpress miR-152 in mice 6 weeks before DOX treatment, using a dose mimicking the concentrations used in the clinics. In response to DOX injection, miR-152 was significantly decreased in murine hearts and cardiomyocytes. After DOX treatment, mice with miR-152 overexpression in the hearts developed less cardiac dysfunction, oxidative stress, inflammation, and myocardial apoptosis. Furthermore, we found that miR-152 overexpression attenuated DOX-related oxidative stress, inflammation, and cell loss in cardiomyocytes, whereas miR-152 knockdown resulted in oxidative stress, inflammation, and cell loss in cardiomyocytes. Mechanistically, this effect of miR-152 was dependent on the activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in response to DOX. Notably, Nrf2 deficiency blocked the protective effects of miR-152 against DOX-related cardiac injury in mice. In conclusion, miR-152 protected against DOX-induced cardiotoxicity via the activation of the Nrf2 signaling pathway. These results suggest that miR-152 may be a promising therapeutic target for the treatment of DOX-induced cardiotoxicity.

scholarly journals Two triterpenoids from Rubus fraxinifolius leaves and their tyrosinase and elastase inhibitory activities

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yesi Desmiaty ◽  
Muhammad Hanafi ◽  
Fadlina Chany Saputri ◽  
Berna Elya ◽  
Eko Aditya Rifai ◽  
...  
Keyword(s):  
Biological Activities ◽  
2D Nmr ◽  
Skin Aging ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Dioic Acid ◽  
Spectroscopic Analyses ◽  
Reported Data ◽  
Therapeutic Compounds ◽  
Organic Resources

AbstractNumerous therapeutic compounds have been isolated from naturally abundant organic resources, which may offer economical and sustainable sources of compounds with safe and efficacious biological activities. In the cosmetics industry, natural compounds with anti-aging activities are eagerly sought. Thus, we prepared various extracts from Rubus fraxinifolius leaves and used enzyme inhibition assays to isolate compounds with protective effects against skin aging. Two triterpenoids were isolated from Rubus fraxinifolius Poir. leaves. The structures were characterized by spectroscopic analyses (LC-ESI-MS, 1D/2D NMR) and comparison to reported data. Compound 1 and 2 were determined as 2,3-O-ethyleneglycol, 19-hydroxyurs-12-en-23,28-dioic acid and 2,3-O-propanediol,19-hydroxyurs-12-en-28-oic acid. Methanol extract and isolates were assessed for their inhibitory effects on elastase and tyrosinase. Compounds 1 and 2 inhibited elastase with IC50 122.199 µg/mL and 98.22 µg/mL, and also inhibited tyrosinase with IC50 207.79 µg/mL and 221.51 µg/mL, respectively. The molecular docking proved that both compounds have affinities toward the enzymes.

scholarly journals Geniposide Protects against Obesity-Related Cardiac Injury through AMPKα- and Sirt1-Dependent Mechanisms

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Zhen-Guo Ma ◽  
Chun-Yan Kong ◽  
Peng Song ◽  
Xin Zhang ◽  
Yu-Pei Yuan ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Morphological Changes ◽  
Cardiac Injury ◽  
Therapeutic Drug ◽  
Myocardial Inflammation ◽  
Protective Effects ◽  
Inhibitory Effects

Our previous study found that geniposide, an agonist of glucagon-like peptide-1 receptor (GLP-1R), protected against cardiac hypertrophy via the activation of AMP-activated protein kinase α (AMPKα). However, the effects of geniposide on obesity-related cardiac injury remain unknown. Here, we examine whether geniposide attenuates obesity-related cardiac dysfunction. Adult mice were fed a high-fat diet (HFD) for 24 weeks to induce obesity, with the last 3 weeks including a 21-day treatment with geniposide. Morphological changes, cardiac function, and remodeling were assessed. HFD-induced metabolic syndrome, featured as obesity, hyperglycemia, and cardiac hypertrophy, was prevented by geniposide treatment. Geniposide preserved cardiac function in the obese mice. Furthermore, geniposide attenuated myocardial inflammation and myocyte apoptosis induced by HFD. Geniposide activated AMPKα and sirtuin (Sirt1) in vivo and in vitro. Ampkα deficiency reversed the inhibitory effects of geniposide on cell loss. Sirt1 deficiency abolished the inhibitory effects of geniposide on inflammation in the cardiomyocytes. Geniposide completely lost its protective effects on Ampkα knockout mice after Sirt1 deficiency achieved by a nanoparticle transfection reagent. The activation of Sirt1 by geniposide was abolished by Glp-1r deficiency in vitro. Geniposide reverses molecular pathology and cardiac dysfunction via both AMPKα- and Sirt1-dependent mechanisms. Geniposide is a potential therapeutic drug for cardiovascular complications induced by obesity.

Sign in / Sign up

Export Citation Format

Share Document