scholarly journals Licochalcone D Ameliorates Oxidative Stress-Induced Senescence via AMPK Activation

2021 ◽  
Vol 22 (14) ◽  
pp. 7324
Author(s):  
Nagarajan Maharajan ◽  
Chitra Devi Ganesan ◽  
Changjong Moon ◽  
Chul-Ho Jang ◽  
Won-Keun Oh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Tissue ◽  
Ampk Activation ◽  
Expression Levels ◽  
Glycation End Products ◽  
Marrow Mesenchymal Stem Cells ◽  
Cardioprotective Effects ◽  
Double Time

Increased oxidative stress is a crucial factor for the progression of cellular senescence and aging. The present study aimed to investigate the effects of licochalcone D (Lico D) on oxidative stress-induced senescence, both in vitro and in vivo, and explore its potential mechanisms. Hydrogen peroxide (200 µM for double time) and D-galactose (D-Gal) (150 mg/kg) were used to induce oxidative stress in human bone marrow-mesenchymal stem cells (hBM-MSCs) and mice, respectively. We performed the SA-β-gal assay and evaluated the senescence markers, activation of AMPK, and autophagy. Lico D potentially reduced oxidative stress-induced senescence by upregulating AMPK-mediated activation of autophagy in hBM-MSCs. D-Gal treatment significantly increased the expression levels of senescence markers, such as p53 and p21, in the heart and hippocampal tissues, while this effect was reversed in the Lico D-treated animals. Furthermore, a significant increase in AMPK activation was observed in both tissues, while the activation of autophagy was only observed in the heart tissue. Interestingly, we found that Lico D significantly reduced the expression levels of the receptors for advanced glycation end products (RAGE) in the hippocampal tissue. Taken together, our findings highlight the antioxidant, anti-senescent, and cardioprotective effects of Lico D and suggest that the activation of AMPK and autophagy ameliorates the oxidative stress-induced senescence.

scholarly journals Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo

2021 ◽  
Author(s):  
yuhan liu ◽  
jiabin zhou ◽  
yingying luo ◽  
jinxiao li ◽  
luorui shang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Nlrp3 Inflammasome ◽  
Epithelial Cell Line ◽  
Protective Mechanism ◽  
Expression Levels ◽  
Nrf2 Activation

Abstract Background Honokiol (HKL) has been reported to ameliorate lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, its potential mechanism imparting the protective effects remains unclear. In this study, the protective mechanism of HKL on LPS-induced ALI was explored in vivo and in vitro. Methods In vivo, the SD rats were intratracheally instilled with LPS (5 mg/kg) to establish an acute lung injury model and then treated with HKL (1.25/2.5/5 mg/kg) or ML385 (30 mg/kg) intraperitoneally. In vitro, the human bronchial epithelial cell line (BEAS-2B) was stimulated with LPS and ATP to induce pyroptosis and treated with HKL (12.5/25/50 µM). Small interfering RNA (siRNA) technique was used to knockdown Nrf2 in BEAS-2B cells. The protein and mRNA expression levels of Nrf2, HO-1, NLRP3, ASC, CASP1, and GSDMD in cells and lung tissues were detected by western blot and real time-PCR. The expression levels of interleukin (IL)-1β, IL-18, MPO, MDA, and SOD in bronchoalveolar lavage fluid (BALF) and supernatant were determined by ELISA. The degree of pathological injury of lung tissue was evaluated by H&E staining. Results The results showed that HKL could alleviate the oxidative stress and inflammatory responses by regulating the levels of MPO, MDA, SOD, IL-1β, IL-18 in supernatant. And HKL inhibited the expression levels of NLRP3, ASC, CASP1, GSDMD via activation of Nrf2 in BEAS-2B cells. Further studies revealed that HKL could attenuate the pathological injury in LPS-induced ALI rats and the molecular mechanism was consistent with the results in vitro. Conclusions Our study demonstrated that HKL could alleviate LPS-induced ALI by reducing the oxidative stress and inhibiting NLRP3 inflammasome-mediated pyroptosis, which was partly dependent on the Nrf2 activation.

scholarly journals Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yuhan Liu ◽  
Jiabin Zhou ◽  
Yingying Luo ◽  
Jinxiao Li ◽  
Luorui Shang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Nlrp3 Inflammasome ◽  
Epithelial Cell Line ◽  
Protective Mechanism ◽  
Expression Levels ◽  
Nrf2 Activation

Abstract Background Honokiol (HKL) has been reported to ameliorate lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, its potential mechanism of its protective effects remains unclear. In this study, the protective mechanism of HKL on LPS-induced ALI was explored in vivo and in vitro. Methods In vivo, the SD rats were intratracheally instilled with LPS (5 mg/kg) to establish an acute lung injury model and then treated with HKL (1.25/2.5/5 mg/kg) or ML385 (30 mg/kg) intraperitoneally. In vitro, the human bronchial epithelial cell line (BEAS-2B) was stimulated with LPS and ATP to induce pyroptosis and treated with HKL (12.5/25/50 μM). Small interfering RNA (siRNA) technique was used to knockdown Nrf2 in BEAS-2B cells. The protein and mRNA expression levels of Nrf2, HO-1, NLRP3, ASC, CASP1, and GSDMD in cells and lung tissues were detected by western blot and real time-PCR. The expression levels of interleukin (IL)-1β, IL-18, MPO, MDA, and SOD in bronchoalveolar lavage fluid (BALF) and supernatant were determined by ELISA. The degree of pathological injury of lung tissue was evaluated by H&E staining. Results The results showed that HKL could alleviate oxidative stress and inflammatory responses by regulating the levels of MPO, MDA, SOD, IL-1β, IL-18 in supernatant. And it could also inhibit the expression levels of NLRP3, ASC, CASP1, GSDMD via activation of Nrf2 in BEAS-2B cells. Further studies revealed that HKL could attenuate the pathological injury in LPS-induced ALI rats, and the molecular mechanism was consistent with the results in vitro. Conclusions Our study demonstrated that HKL could alleviate LPS-induced ALI by reducing the oxidative stress and inhibiting NLRP3 inflammasome-mediated pyroptosis, which was partly dependent on the Nrf2 activation. Graphical Abstract

scholarly journals Cardioprotective effects of alantolactone on isoproterenol-induced cardiac injury and cobalt chloride-induced cardiomyocyte injury

2022 ◽  
Vol 36 ◽  
pp. 205873842110519
Author(s):  
Miaomiao Liu ◽  
Panpan Liu ◽  
Bin Zheng ◽  
Yu Liu ◽  
Li Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cobalt Chloride ◽  
Troponin I ◽  
Cardiac Injury ◽  
Calcium Overload ◽  
Patch Clamp Technique ◽  
Stress Injury ◽  
Cardioprotective Effects

Objectives Alantolactone (AL) is a compound extracted from the roots of Inula Racemosa that has shown beneficial effects in cardiovascular disease. However, the cardioprotective mechanism of AL against hypoxic/ischemic (H/I) injury is still unclear. This research aimed to determine AL’s ability to protect the heart against isoproterenol (ISO)-induced MI injury in vivo and cobalt chloride (CoCl2) induced H/I injury in vitro. Methods Electrocardiography (ECG), lactate dehydrogenase (LDH), creatine kinase (CK), and cardiac troponin I (cTnI) assays in addition to histological analysis of the myocardium were used to investigate the effects of AL in vivo. Influences of AL on L-type Ca2+ current (ICa-L) in isolated rat myocytes were observed by the patch-clamp technique. Furthermore, cell viability, apoptosis, oxidative stress injury, mitochondrial membrane potential, and intracellular Ca2+ concentration were examined in vitro. Results The results indicated that AL treatment ameliorated the morphological and ECG changes associated with MI, and decreased levels of LDH, CK, and cTnI. Furthermore, pretreatment with AL elevated antioxidant enzyme activity and suppressed ROS production. AL prevented H/I-induced apoptosis, mitochondria damage, and calcium overload while reducing ICa-L in a concentration and time dependent fashion. The 50% inhibiting concentration (IC50) and maximal inhibitory effect (Emax) of AL were 17.29 μmol/L and 57.73 ± 1.05%, respectively. Conclusion AL attenuated MI-related injury by reducing oxidative stress, apoptosis, calcium overload, and mitochondria damage. These cardioprotective effects may be related to the direct inhibition of ICa-L.

scholarly journals Extracellular vesicles produced by bone marrow mesenchymal stem cells attenuate renal fibrosis, in part by inhibiting the RhoA/ROCK pathway, in a UUO rat model

2020 ◽  
Author(s):  
Zhengzhou Shi ◽  
Qi Wang ◽  
Youbo Zhang ◽  
Dapeng Jiang
Keyword(s):  
Oxidative Stress ◽  
Extracellular Vesicles ◽  
Renal Fibrosis ◽  
Sham Group ◽  
Rock Inhibitor ◽  
Marrow Mesenchymal Stem Cells ◽  
Hk2 Cells ◽  
Tgf Β1

Abstract Background Renal interstitial fibrosis is a critical symptom of chronic kidney disease (CKD) that is associated with high incidence. Extracellular vesicles produced by bone marrow mesenchymal stem cells (BMSC-EVs) can play important roles in the repair of injured tissues. However, no reports have investigated the role and mechanism of BMSC-EVs in renal fibrosis. Thus, we hypothesized that BMSC-EVs containing milk fat globule-EGF factor-8 (MFG-E8) could attenuate renal fibrosis by inhibiting the RhoA/ROCK pathway.Methods We investigated whether BMSC-EVs have antifibrotic effects in a rat model of renal fibrosis-rats subjected to unilateral ureteral obstruction (UUO) - as well as in cultured HK2 cells. In vivo, Sprague-Dawley (SD) rats were randomly divided into 6 groups: Sham group, Sham + EVs group, UUO group, UUO + EVs group, UUO + EVs Ctrl group, and UUO + EVs shMFGE8 group. In vitro, extracellular vesicles from BMSCs were collected and co-cultured with HK2 cells during transforming growth factor-β1 (TGF-β1) treatment. Besides, HK2 cells co-cultured with TGF-β1 were also treated with the ROCK inhibitor, Y-27632. Results Compared with the Sham group, UUO rats displayed fibrotic abnormalities, accompanied by increased expression of α-SMA and Fibronectin, and decreased expression of E-cadherin. Both molecular and pathological changes suggested an increased inflammation in damaged kidneys. Oxidative stress, as evidenced by decreased levels of SOD1 and Catalase, was also observed in UUO kidneys. In addition, activation of cleaved caspase-3 and PARP1 and increased apoptosis in the proximal tubules confirmed tubular cell apoptosis in the UUO group. All of these phenotypes exhibited by UUO rats were suppressed by treatment with BMSC-EVs. However, the protective effect of BMSC-EVs was completely abolished by inhibition of MFG-E8. Consistent with the in vivo results, treatment with BMSC-EVs reduced inflammation, oxidative stress, apoptosis, and fibrosis in HK-2 cells stimulated with TGF-β1 in vitro . Interestingly, treatment with Y-27632, a ROCK inhibitor, protected HK-2 cells against inflammation and fibrosis, although oxidative stress and apoptosis were unchanged. Conclusions In summary, our results show that BMSC-EVs containing MFG-E8 attenuate renal fibrosis, partly through RhoA/ROCK pathway inhibition.

Abstract 176: Intravenous Infusion Of Glycated End Products Induces Cardiac Remodeling And Fibrosis Through RAGE Mediated Oxidative Stress

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Umadevi Subramanian ◽  
Elangovan Vellaichamy
Keyword(s):  
Oxidative Stress ◽  
Cardiac Remodeling ◽  
Intravenous Infusion ◽  
Lipid Peroxides ◽  
Heart Tissue ◽  
Diabetic Patients ◽  
Long Term Effects ◽  
End Products

Advanced glycation end products (AGEs) play a major role in the development of cardiovascular disorders in diabetic patients. Growing evidence has shown that the western diet is a plentiful source of exogenous AGEs. However, the direct impact of these AGEs on cardiac remodeling process is not well understood. Thus, the present study was intended to scrutinize the long term effects of circulating AGEs on cardiac extracellular matrix alterations both in vivo , Wistar rats, and in vitro , H9C2(2-1) cardiac myofibroblast cells. In vivo Rats (n=8/group) were administered with an intravenous infusion of in vitro prepared glycated-RSA (AGEs-RSA) (50 mg/kg /day for 30 days), while control animals received the non-glycated-RSA. In vitro , H9C2 (2-1) cardiac myofibroblast cells were exposed to AGEs (100µg/ml) for 24 hours. Upon AGEs infusion, a significant increase in fibrosis (3-fold, p<0.01) with increased expression of matrix genes MMP-2 and -9 (P<0.01, respectively), CTGF (p<0.01) and TGF-β (P<0.01) was found in the heart tissues compared to non-glycated-RSA infused rats. Furthermore, an increase in mRNA and protein expression of RAGE (receptor for AGE), and NADPH oxidase (NOX-p47 phox subunit), iNOS and NF-κB was observed in the heart tissue of AGEs infused rats. Furthermore, induction of lipid peroxides (p<0.001) were also found in the heart tissue of AGEs-RSA infused rats. Similarly, H9C2 (2-1) cells exposed to AGEs-RSA demonstrated a significant increase in ROS release (DCF fluorescence, p<0.001) with augmented expression of RAGE ( P <0.01) and NOX-p47 phox ( p <0.001) compared to untreated cells. Whereas, cells pre-treated with N-Acetyl cysteine and RAGE neutralizing antibody significantly impeded the NOX expression ( p <0.01) and attenuated the up-regulation of RAGE and NF-κB in AGEs-RSA treated H9C2 cells. Thus, the results of the present study demonstrated the deleterious effect of AGEs that directly induces oxidative stress and matrix derangement in heart tissue even when ingested through exogenous sources.

scholarly journals Galactose-Induced Skin Aging: The Role of Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Bauyrzhan Umbayev ◽  
Sholpan Askarova ◽  
Aigul Almabayeva ◽  
Timur Saliev ◽  
Abdul-Razak Masoud ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Skin Diseases ◽  
Skin Aging ◽  
Covalent Attachment ◽  
Advanced Glycation ◽  
Glycation End Products

Skin aging has been associated with a higher dietary intake of carbohydrates, particularly glucose and galactose. In fact, the carbohydrates are capable of damaging the skin’s vital components through nonenzymatic glycation, the covalent attachment of sugar to a protein, and subsequent production of advanced glycation end products (AGEs). This review is focused on the role of D-galactose in the development of skin aging and its relation to oxidative stress. The interest in this problem was dictated by recent findings that used in vitro and in vivo models. The review highlights the recent advances in the underlying molecular mechanisms of D-galactose-mediated cell senescence and cytotoxicity. We have also proposed the possible impact of galactosemia on skin aging and its clinical relevance. The understanding of molecular mechanisms of skin aging mediated by D-galactose can help dermatologists optimize methods for prevention and treatment of skin senescence and aging-related skin diseases.

scholarly journals Knockout RAGE alleviates cardiac fibrosis through repressing endothelial-to-mesenchymal transition (EndMT) mediated by autophagy

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Lu Zhang ◽  
Jiaqi He ◽  
Junyan Wang ◽  
Jing Liu ◽  
Zixin Chen ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Cardiac Fibrosis ◽  
Smooth Muscle Actin ◽  
Heart Tissue ◽  
Mesenchymal Transition ◽  
Glycation End Products ◽  
Endothelial To Mesenchymal Transition ◽  
Related Proteins

AbstractEndothelial-to-mesenchymal transition (EndMT) has been shown to contribute to cardiac fibrosis and heart failure (HF). Recent studies have demonstrated that EndMT is regulated by autophagy, and we previously showed suppression of excessive autophagy and alleviation of cardiac fibrosis in HF mice with inactivated receptor for advanced glycation end products (RAGE). Thus, we investigated whether reduced cardiac fibrosis due to RAGE knockout occurred by inhibiting EndMT mediated by excessive autophagy. We found a decrease in endothelial cells (CD31+/VE-Cadherin+) and an increase in cells co-expressing CD31 and α-smooth muscle actin (α-SMA, myofibroblast marker) at 8 weeks in heart tissue of mice subjected to transverse aortic constriction (TAC), which implied EndMT. Knockout RAGE decreased EndMT accompanied by decreased expression of autophagy-related proteins (LC3BII/I and Beclin 1), and alleviated cardiac fibrosis and improved cardiac function in TAC mice. Moreover, 3-methyladenine (3-MA) and chloroquine (CQ), inhibitors of autophagy, attenuated EndMT, and cardiac fibrosis in TAC mice. Importantly, EndMT induced by AGEs could be blocked by autophagy inhibitor in vivo and in vitro. These results suggested that AGEs/RAGE-autophagy-EndMT axis involved in the development of cardiac fibrosis and knockout RAGE ameliorated cardiac fibrosis through decreasing EndMT regulated by autophagy, which could be a promising therapeutic strategy for HF.

scholarly journals DDRE-16. CYSTEINE IS AN ESSENTIAL AMINO ACID IN GLIOMAS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. i9-i9
Author(s):  
Victor Ruiz-Rodado ◽  
Tyrone Dowdy ◽  
Jinkyu Yung ◽  
Ana Dios-Esponera ◽  
Adrian Lita ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amino Acid ◽  
Essential Amino Acid ◽  
Antioxidant Response ◽  
Dietary Interventions ◽  
Expression Levels ◽  
Transsulfuration Pathway ◽  
Proliferation In Vitro

Abstract BACKGROUND Cysteine is a non-essential amino acid, since it can be synthetized from methionine through the transsulfuration pathway; moreover, cysteine is also uptake from the diet as cystine. We have investigated the metabolism of cysteine in glioma cell lines, and how cysteine/cystine-deprivation alters their antioxidant response in addition to the effect of this nutrient restriction to viability and proliferation in vitro and in vivo. METHODS Cysteine metabolism was investigated through LCMS-based 13C-tracing experiments involving different probes such as 13C-methyl-Methionine, 13C-C3-Cysteine, 13C-C3,3’-Cystine, 13C-C3-Serine and 13C-U-Glutamine and the expression levels of key enzymes in the transsulfuration pathway were also explored. Finally, a mouse model of IDH1 mutant glioma was subjected to a cysteine/cystine-free diet and tumor metabolism was analyzed by LCMS. RESULTS We demonstrated that exogenous cysteine/cystine are crucial for glutathione synthesis, and impact growth and viability. We also found that methionine cycle is disconnected from the transsulfuration pathway based on 13C-tracing data and protein expression levels of cystathionine synthase and cystathioninase. Accordingly, cysteine-related metabolites such as GSH, involved in REDOX hemostasis, are downregulated, revealing a hypersensitive phenotype to ROS. Animal models upon a cysteine/cystine-free diet experienced an increase in survival and elevated levels of oxidative stress in tumor tissue. CONCLUSION This results presented herein reveal an alternative therapeutic approach combining cysteine/cysteine-deprivation diets and treatments involving ROS production by limiting the ability of glioma cells to quench oxidative stress through dietary interventions.

scholarly journals BMSCs differentiated into neurons, astrocytes and oligodendrocytes alleviated the inflammation and demyelination of EAE mice models

2020 ◽  
Author(s):  
Guo-yi Liu ◽  
Yan Wu ◽  
Fan-yi Kong ◽  
Shu Ma ◽  
Li-yan Fu ◽  
...  
Keyword(s):  
Disease Incidence ◽  
Inflammatory Factors ◽  
Autoimmune Encephalomyelitis ◽  
Expression Levels ◽  
Neuroinflammatory Disease ◽  
Tnf Α ◽  
Marrow Mesenchymal Stem Cells ◽  
Effective Therapeutic Strategy

AbstractMultiple sclerosis (MS) is a complex, progressive neuroinflammatory disease associated with autoimmunity. Currently, effective therapeutic strategy was poorly found in MS. Experimental autoimmune encephalomyelitis (EAE) is widely used to study the pathogenesis of MS. Previous studies have shown that bone marrow mesenchymal stem Cells (BMSCs) transplantation could treat EAE animal models, but the mechanism was divergent. Here, we systematically evaluated whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes to alleviate the symptoms of EAE mice. We used Immunofluorescence staining to detect MAP-2 neurons marker, GFAP astrocytes marker, and MBP oligodendrocytes marker expression to evaluate whether BMSCs can differentiate. The effect of BMSCs transplantation on inflammatory cell invasion and demyelination in EAE mice were detected by Hematoxylin-Eosin (H&E) and Luxol Fast Blue (LFB) staining. Inflammatory factors expression was detected by ELISA and RT-qPCR. Our results showed that BMSCs could be induced to differentiate into neuron cells, astrocytes and oligodendrocyte in vivo and in vitro. In addition, BMSCs transplant improved the survival rate and weight, and reduced neurological function scores and disease incidence of EAE mice. Moreover, BMSCs transplant alleviated the inflammation and demyelination of EAE mice. Finally, we found that BMSCs transplantation down-regulated the expression levels of pro-inflammatory factors TNF-α, IL-1β and IFN-γ, and up-regulated the expression levels of anti-inflammatory factors IL-10 and TGF-β. In conclusion, this study found that BMSCs could alleviate the inflammatory response and demyelination in EAE mice, which may be achieved by the differentiation of BMSCs into neurons, astrocytes and oligodendrocytes in EAE mice.

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