Ferulic Acid Alleviates Oxidative Stress-Induced Cardiomyocyte Injury by the Regulation of miR-499-5p/p21 Signal Cascade

Objective. To investigate the protective effects and regulatory mechanisms of ferulic acid on oxidative stress-induced cardiomyocyte injury. Methods. We established a cardiomyocyte oxidative stress cell model by H2O2 treatment and a mouse heart injury model by isoprenaline infusion of male C57BL/6 mice. Ferulic acid was applied to treat oxidative stress-induced cardiomyocyte injury. DHE staining was used to detect ROS production. DNA fragmentation, TUNEL assay, and cleaved caspase-3 were used to analyze cell apoptosis. Real-time PCR and Western blotting were used to analyze miRNA and protein levels to investigate the regulatory mechanisms of ferulic acid on oxidative stress-induced cardiomyocyte injury. Results. Ferulic acid pretreatment significantly inhibited H2O2- and isoprenaline-induced oxidative stress and cell apoptosis by promoting miR-499-5p expression and inhibiting p21 expression. MiR-499-5p inhibition reversed the protective effects of ferulic acid. Further study found that ferulic acid could also attenuate isoprenaline-induced mouse heart fibrosis and cell apoptosis by reducing oxidative stress, inflammation, and apoptosis in vivo. Conclusions. We proved that ferulic acid protects cardiomyocytes from oxidative stress-induced injury by regulating the miR-499-5p/p21signaling pathway, which provides insight into the clinical application of ferulic acid in the treatment of cardiovascular diseases.

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In Vitro and In Vivo Protective Effects of Lentil (Lens culinaris) Extract against Oxidative Stress-Induced Hepatotoxicity

Molecules ◽

10.3390/molecules27010059 ◽

2021 ◽

Vol 27 (1) ◽

pp. 59

Author(s):

Yeon-Seop Jung ◽

So-Hee Lee ◽

So Young Chun ◽

Dae Hwan Kim ◽

Byung Ik Jang ◽

...

Keyword(s):

Oxidative Stress ◽

Serum Levels ◽

Liver Cells ◽

Dependent Manner ◽

Protective Effects ◽

H2o2 Treatment ◽

Antioxidant Genes ◽

Hepatic Diseases

Excessive oxidative stress plays a role in hepatotoxicity and the pathogenesis of hepatic diseases. In our previous study, the phenolic extract of beluga lentil (BLE) showed the most potent in vitro antioxidant activity among extracts of four common varieties of lentils; thus, we hypothesized that BLE might protect liver cells against oxidative stress-induced cytotoxicity. BLE was evaluated for its protective effects against oxidative stress-induced hepatotoxicity in AML12 mouse hepatocytes and BALB/c mice. H2O2 treatment caused a marked decrease in cell viability; however, pretreatment with BLE (25–100 μg/mL) for 24 h significantly preserved the viability of H2O2-treated cells up to about 50% at 100 μg/mL. As expected, BLE dramatically reduced intracellular reactive oxygen species (ROS) levels in a dose-dependent manner in H2O2-treated cells. Further mechanistic studies demonstrated that BLE reduced cellular ROS levels, partly by increasing expression of antioxidant genes. Furthermore, pretreatment with BLE (400 mg/kg) for 2 weeks significantly reduced serum levels of alanine transaminase and triglyceride by about 49% and 40%, respectively, and increased the expression and activity of glutathione peroxidase in CCl4-treated BALB/c mice. These results suggest that BLE protects liver cells against oxidative stress, partly by inducing cellular antioxidant system; thus, it represents a potential source of nutraceuticals with hepatoprotective effects.

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Ethyl Vanillin Protects against Kidney Injury in Diabetic Nephropathy by Inhibiting Oxidative Stress and Apoptosis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/2129350 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Yuna Tong ◽

Shan Liu ◽

Rong Gong ◽

Lei Zhong ◽

Xingmei Duan ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Cell Apoptosis ◽

Cell Model ◽

Critical Role ◽

Kidney Injury ◽

Related Factor ◽

Ethyl Vanillin

Diabetes-induced oxidative stress and apoptosis is regarded as a critical role in the pathogenesis of diabetic nephropathy (DN). Treating diabetes-induced kidney damage and renal dysfunction has been thought a promising therapeutic option to attenuate the development and progression of DN. In this study, we investigated the renoprotective effect of ethyl vanillin (EVA), an active analogue of vanillin isolated from vanilla beans, on streptozotocin- (STZ-) induced rat renal injury model and high glucose-induced NRK-52E cell model. The EVA treatment could strongly improve the deterioration of renal function and kidney cell apoptosis in vivo and in vitro. Moreover, treating with EVA significantly decreased the level of MDA and reactive oxygen species (ROS) and stabilized antioxidant enzyme system in response to oxidative stress by enhancing the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in vivo and in vitro. Furthermore, EVA also markedly suppressed cleaved caspase-3, Bax, and nuclear transcription factor erythroid 2-related factor (Nrf2) expression in STZ-induced rats. Therefore, these results of our investigation provided that EVA might protect against kidney injury in DN by inhibiting oxidative stress and cell apoptosis.

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In vivo protective effects of ferulic acid ethyl ester against amyloid-beta peptide 1–42-induced oxidative stress

Journal of Neuroscience Research ◽

10.1002/jnr.20879 ◽

2006 ◽

Vol 84 (2) ◽

pp. 418-426 ◽

Cited By ~ 77

Author(s):

Marzia Perluigi ◽

Gururaj Joshi ◽

Rukhsana Sultana ◽

Vittorio Calabrese ◽

Carlo De Marco ◽

...

Keyword(s):

Oxidative Stress ◽

Ferulic Acid ◽

Ethyl Ester ◽

Amyloid Beta ◽

Acid Ethyl Ester ◽

Amyloid Beta Peptide ◽

Protective Effects ◽

Beta Peptide ◽

Ferulic Acid Ethyl Ester

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Cardamonin Alleviates Oxidative Stress, Cell Apoptosis Level and Extracellular Matrix Degradation by Inhibiting NF-kb in ILβ-1 -Induced Chondrocytes

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2299 ◽

2020 ◽

Vol 10 (5) ◽

pp. 589-595

Author(s):

Chongxin Li ◽

Wei Zeng

Keyword(s):

Oxidative Stress ◽

Extracellular Matrix ◽

Cell Apoptosis ◽

Cell Model ◽

Joint Disease ◽

Protective Effects ◽

Matrix Degradation ◽

Extracellular Matrix Degradation ◽

Apoptosis Detection ◽

Apoptosis Level

Currently, osteoarthritis as degenerative chronic joint disease remains unsolved and finding the effective targeting therapeutic agent is pressing. Therefore, in this research, we aimed to investigate the effects of cardamonin, the NF-kb inhibitor, in cell model of osteoarthritis. IL-1β that induced chondrocytes served as the cell model of osteoarthritis. The cells were divided into control, IL-1β and IL-1+ cardamonin groups. Western blot assays were performed for assessment of protein expression level and PCR for gene level. Flow cytometry was used for cell apoptosis detection. MDA, LDH SOD and ROS were detected by corresponding kits. The NF-kb was activated by IL-1. The entrance of NF-kb into cell nucleus was inhibited by cardamonin in IL-1β-induced cells. The MDA, LDH and ROS were increased by IL-1β and SOD was down-regulated by IL-1β. This effect of IL-1β was reduced by cardamonin. The cell apoptosis and pro-apoptosis proteins were increased and BCl-2 was down-regulated in IL-1β-induced cells. After cardamonin treatment, this effect was inhibited. The extracellular matrix degradation as well as the relative degradation enzymes was elevated by IL-1β, and this effect was further inhibited by cardamonin as well. Cardamonin exerted protective effects via alleviating oxidative stress, cell apoptosis level and extracellular matrix degradation by inhibiting NF-kb in IL-1β-induced chondrocytes. Cardamonin as NF-kb inhibitor was a promising drug for therapy of osteoarthritis.

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Protective Effect of Triphala against Oxidative Stress-Induced Neurotoxicity

BioMed Research International ◽

10.1155/2021/6674988 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Wanchen Ning ◽

Simin Li ◽

Jokyab Tsering ◽

Yihong Ma ◽

Honghong Li ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Activities ◽

Cell Model ◽

Neuroprotective Effect ◽

Flow Cytometric Analysis ◽

Mitogen Activated Protein Kinase ◽

Protective Effects ◽

Zebrafish Model

Background. Oxidative stress is implicated in the progression of many neurological diseases, which could be induced by various chemicals, such as hydrogen peroxide (H2O2) and acrylamide. Triphala is a well-recognized Ayurvedic medicine that possesses different therapeutic properties (e.g., antihistamine, antioxidant, anticancer, anti-inflammatory, antibacterial, and anticariogenic effects). However, little information is available regarding the neuroprotective effect of Triphala on oxidative stress. Materials and Methods. An in vitro H2O2-induced SH-SY5Y cell model and an in vivo acrylamide-induced zebrafish model were established. Cell viability, apoptosis, and proliferation were examined by MTT assay, ELISA, and flow cytometric analysis, respectively. The molecular mechanism underlying the antioxidant activity of Triphala against H2O2 was investigated dose dependently by Western blotting. The in vivo neuroprotective effect of Triphala on acrylamide-induced oxidative injury in Danio rerio was determined using immunofluorescence staining. Results. The results indicated that Triphala plays a neuroprotective role against H2O2 toxicity in inhibiting cell apoptosis and promoting cell proliferation. Furthermore, Triphala pretreatment suppressed the phosphorylation of the mitogen-activated protein kinase (MARK) signal pathway (p-Erk1/2, p-JNK1/2, and p-p38), whereas it restored the activities of antioxidant enzymes (superoxide dismutase 1 (SOD1) and catalase) in the H2O2-treated SH-SY5Y cells. Consistently, similar protective effects of Triphala were observed in declining neuroapoptosis and scavenging free radicals in the zebrafish central neural system, possessing a critical neuroprotective property against acrylamide-induced oxidative stress. Conclusion. In summary, Triphala is a promising neuroprotective agent against oxidative stress in SH-SY5Y cells and zebrafishes with significant antiapoptosis and antioxidant activities.

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Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

Molecular Medicine ◽

10.1186/s10020-021-00332-0 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Jian-Ping Zhang ◽

Wei-Jing Zhang ◽

Miao Yang ◽

Hua Fang

Keyword(s):

Cell Apoptosis ◽

Ischemia Reperfusion Injury ◽

Glycogen Synthase ◽

Ischemia Reperfusion ◽

Inflammatory Factors ◽

Therapeutic Effects ◽

Protective Effects ◽

Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

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Protective Effects of Taraxacum officinale L. (Dandelion) Root Extract in Experimental Acute on Chronic Liver Failure

Antioxidants ◽

10.3390/antiox10040504 ◽

2021 ◽

Vol 10 (4) ◽

pp. 504

Author(s):

Iulia Olimpia Pfingstgraf ◽

Marian Taulescu ◽

Raluca Maria Pop ◽

Remus Orăsan ◽

Laurian Vlase ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Failure ◽

Tissue Injury ◽

Taraxacum Officinale ◽

Chronic Liver ◽

Root Extract ◽

Protective Effects ◽

Stress Tests ◽

Chronic Liver Failure

Background: Taraxacum officinale (TO) or dandelion has been frequently used to prevent or treat different liver diseases because of its rich composition in phytochemicals with demonstrated effect against hepatic injuries. This study aimed to investigate the possible preventing effect of ethanolic TO root extract (TOERE) on a rat experimental acute on chronic liver failure (ACLF) model. Methods: Chronic liver failure (CLF) was induced by human serum albumin, and ACLF was induced in CLF by D-galactosamine and lipopolysaccharide (D-Gal-LPS). Five groups (n = 5) of male Wistar rats (200–250 g) were used: ACLF, ACLF-silymarin (200 mg/kg b.w./day), three ACLF-TO administered in three doses (200 mg, 100 mg, 50 mg/kg b.w./day). Results: The in vivo results showed that treatment with TOERE administered in three chosen doses before ACLF induction reduced serum liver injury markers (AST, ALT, ALP, GGT, total bilirubin), renal tests (creatinine, urea), and oxidative stress tests (TOS, OSI, MDA, NO, 3NT). Histopathologically, TOERE diminished the level of liver tissue injury and 3NT immunoexpression. Conclusions: This paper indicated oxidative stress reduction as possible mechanisms for the hepatoprotective effect of TOERE in ACLF and provided evidence for the preventive treatment.

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Protective Effects of Peroxiredoxin 4 (PRDX4) on Cholestatic Liver Injury

International Journal of Molecular Sciences ◽

10.3390/ijms19092509 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2509 ◽

Cited By ~ 3

Author(s):

Jing Zhang ◽

Xin Guo ◽

Taiji Hamada ◽

Seiya Yokoyama ◽

Yuka Nakamura ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Critical Role ◽

Therapeutic Modality ◽

Protective Effects ◽

Fibrotic Liver ◽

Intrahepatic Bile Ducts ◽

Duct Ligation ◽

Cholestatic Liver Injury

Accumulating evidence indicates that oxidative stress plays a critical role in initiating the progression of inflammatory and fibrotic liver diseases, including cholestatic hepatitis. Peroxiredoxin 4 (PRDX4) is a secretory antioxidase that protects against oxidative damage by scavenging reactive oxygen species (ROS) in both the intracellular compartments and extracellular space. In this study, we examined the in vivo net effects of PRDX4 overexpression in a murine model of cholestasis. To induce cholestatic liver injury, we subjected C57BL/6J wild-type (WT) or human PRDX4 (hPRDX4) transgenic (Tg) mice to sham or bile duct ligation (BDL) surgery for seven days. Our results showed that the liver necrosis area was significantly suppressed in Tg BDL mice with a reduction in the severity of liver injuries. Furthermore, PRDX4 overexpression markedly reduced local and systemic oxidative stress generated by BDL. In addition, suppression of inflammatory cell infiltration, reduced proliferation of hepatocytes and intrahepatic bile ducts, and less fibrosis were also found in the liver of Tg BDL mice, along with a reduced mortality rate after BDL surgery. Interestingly, the composition of the hepatic bile acids (BAs) was more beneficial for Tg BDL mice than for WT BDL mice, suggesting that PRDX4 overexpression may affect BA metabolism during cholestasis. These features indicate that PRDX4 plays an important role in protecting against liver injury following BDL and might be a promising therapeutic modality for cholestatic diseases.

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Abstract 352: Real-time Intravital Optical Imaging Reflects the Dynamic Changes of Oxidative Stress Induced by Cigarette Smoking in Vasculatures

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.352 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Ji Bak Kim ◽

Jiheun Ryu ◽

Joon Woo Song ◽

Dong Joo Oh ◽

DaeGab Gweon ◽

...

Keyword(s):

Oxidative Stress ◽

Cigarette Smoking ◽

Optical Imaging ◽

Real Time ◽

Treated Group ◽

Fluorescence Signal ◽

Ros Production ◽

Protective Effects ◽

Dynamic Changes

Background: Reactive oxygen species (ROS) play a central role in cigarette smoking-induced atherogenesis. The present study aims to assess the smoking-induced acute oxidative stress within vasculatures, and evaluates whether the resveratrol, a natural polyphenol antioxidant, can counteract this ROS production, using a customized, high resolution intravital optical imaging in real-time. Methods and Results: 20-week-old male C57BL/6 mice were divided into four groups according to the preceding administration of resveratrol (R) (25mg/kg via gavage, for 7 days) and exposure to cigarette smoke (CS). To in vivo assess acute oxidative stress in blood vessels, dihydroethidium, which forms a red fluorescence (ethidium, excitation/emission: 520nm/610nm) upon reaction with ROS, was injected intraperitoneally. During CS exposure, temporal changes of fluorescence signals from the mouse cremaster muscle including vasculatures were assessed by intravital optical imaging for 15 minutes. Fluorescence signals were much more pronounced in CS exposed mice than controls (p<0.001). Resveratrol p.o. significantly reduced the CS-induced ROS signals compared to the non-treated group (fluorescence signal to noise ratio, SNR, 2.51±0.09 vs. 12.52±2.116, p=0.0002) (Figure A). Without CS exposure, fluorescence signals in targeted vasculatures were very low showing no difference between groups (SNR, 1.65±0.19 vs. 1.53±0.07, p=0.80) (Figure A). Lipid peroxidation was increased in CS group and significantly attenuated in resveratrol-treated mice (Figure B). Fluorescence microscopy and immunostainings corroborated the in vivo findings. Conclusions: The intravital optical imaging was able to in vivo estimate the dynamic changes of ROS production by CS exposure. Our data demonstrated that even a brief exposure to CS increased oxidative stress in vasculatures promptly, and the resveratrol exerts protective effects against the CS-induced acute oxidative stress.

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Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6746907 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 12

Author(s):

Kaifeng Li ◽

Mengen Zhai ◽

Liqing Jiang ◽

Fan Song ◽

Bin Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Diabetic Cardiomyopathy ◽

High Glucose ◽

Therapeutic Potential ◽

Ros Generation ◽

Protective Effects ◽

Collagen Iii

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

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