The Experts below are selected from a list of 1155 Experts worldwide ranked by ideXlab platform
Qun Shan - One of the best experts on this subject based on the ideXlab platform.
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Troxerutin Protects Kidney Tissue against BDE-47-Induced Inflammatory Damage through CXCR4-TXNIP/NLRP3 Signaling.
Oxidative medicine and cellular longevity, 2018Co-Authors: Qun Shan, Zi-feng Zhang, Gui-hong Zheng, Juan Zhuang, Xin-rui Han, Xin Wen, Shan Wang, Yan-qiu ZhangAbstract:2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) induces oxidative stress in kidney cells, but the underlying mechanism remains poorly understood. Troxerutin, a natural flavonoid, has potential antioxidant and anti-inflammatory efficacy. In this study, we assessed the effect of Troxerutin on kidney damage caused by BDE-47 and investigated the underlying mechanism. The results showed Troxerutin reduced reactive oxygen species (ROS) level and urine albumin-to-creatinine ratio (ACR), decreased the activities of inflammatory factors including cyclooxygenase-2 (COX-2), induced nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) in the kidney tissues of BDE-47-treated mice. Furthermore, Troxerutin significantly weakened the expression of kidney NLRP3 inflammasome containing NLRP3, ASC, and caspase-1, contributing to the decline of IL-1β. Additionally, Troxerutin inhibited the increased protein level of stromal-derived factor-1(SDF-1), C-X-C chemokine ligand 12 receptor 4 (CXCR4), and thioredoxin interaction protein (TXNIP) caused by BDE-47. Specifically, the immunoprecipitation assay indicated that there was a direct interaction between CXCR4 and TXNIP. CXCR4 siRNA and TXNIP siRNA also decreased the inflammatory damage, which was similar to the action of Troxerutin. Our data demonstrated that Troxerutin regulated the inflammatory lesions via CXCR4-TXNIP/NLRP3 inflammasome in the kidney of mice induced by BDE-47.
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Troxerutin protects kidney tissue against bde 47 induced inflammatory damage through cxcr4 txnip nlrp3 signaling
Oxidative Medicine and Cellular Longevity, 2018Co-Authors: Zi-feng Zhang, Gui-hong Zheng, Qun Shan, Juan Zhuang, Yan-qiu Zhang, Xin-rui Han, Xin Wen, Shan Wang, Yuan-lin ZhengAbstract:2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) induces oxidative stress in kidney cells, but the underlying mechanism remains poorly understood. Troxerutin, a natural flavonoid, has potential antioxidant and anti-inflammatory efficacy. In this study, we assessed the effect of Troxerutin on kidney damage caused by BDE-47 and investigated the underlying mechanism. The results showed Troxerutin reduced reactive oxygen species (ROS) level and urine albumin-to-creatinine ratio (ACR), decreased the activities of inflammatory factors including cyclooxygenase-2 (COX-2), induced nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) in the kidney tissues of BDE-47-treated mice. Furthermore, Troxerutin significantly weakened the expression of kidney NLRP3 inflammasome containing NLRP3, ASC, and caspase-1, contributing to the decline of IL-1β. Additionally, Troxerutin inhibited the increased protein level of stromal-derived factor-1(SDF-1), C-X-C chemokine ligand 12 receptor 4 (CXCR4), and thioredoxin interaction protein (TXNIP) caused by BDE-47. Specifically, the immunoprecipitation assay indicated that there was a direct interaction between CXCR4 and TXNIP. CXCR4 siRNA and TXNIP siRNA also decreased the inflammatory damage, which was similar to the action of Troxerutin. Our data demonstrated that Troxerutin regulated the inflammatory lesions via CXCR4-TXNIP/NLRP3 inflammasome in the kidney of mice induced by BDE-47.
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Troxerutin Reduces Kidney Damage against BDE-47-Induced Apoptosis via Inhibiting NOX2 Activity and Increasing Nrf2 Activity.
Oxidative medicine and cellular longevity, 2017Co-Authors: Qun Shan, Zi-feng Zhang, Gui-hong Zheng, Juan Zhuang, Yan-qiu Zhang, Yuan-lin ZhengAbstract:2,2,4,4-Tetrabromodiphenyl ether (BDE-47), one of the persistent organic pollutants, seriously influences the quality of life; however, its pathological mechanism remains unclear. Troxerutin is a flavonoid with pharmacological activity of antioxidation and anti-inflammation. In the present study, we investigated Troxerutin against BDE-47-induced kidney cell apoptosis and explored the underlying mechanism. The results show that Troxerutin reduced renal cell apoptosis and urinary protein secretion in BDE-47-treated mice. Western blot analysis shows that Troxerutin supplement enhanced the ratio of Bcl-2/Bax; inhibited the release of cytochrome c from mitochondria, the activation of procaspase-9 and procaspase-3, and the cleavage of PARP; and reduced FAS, FASL, and caspase-8 levels induced by BDE-47. In addition, Troxerutin decreased the production of reactive oxygen species (ROS) and increased the activities of antioxidative enzymes. Furthermore, Troxerutin blunted Nrf2 ubiquitylation, enhanced the activity of Nrf2, decreased the activity of NOX2, and ameliorated kidney oxidant status of BDE-47-treated mice. Together, these results confirm that Troxerutin could alleviate the cytotoxicity of BDE-47 through antioxidation and antiapoptosis, which suggests that its protective mechanism is involved in the inhibition of apoptosis via suppressing NOX2 activity and increasing Nrf2 signaling pathway.
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Troxerutin Attenuates Enhancement of Hepatic Gluconeogenesis by Inhibiting NOD Activation-Mediated Inflammation in High-Fat Diet-Treated Mice
International journal of molecular sciences, 2016Co-Authors: Zi-feng Zhang, Xin Wang, Gui-hong Zheng, Qun Shan, Shao-hua Fan, Chun-hui Sun, Cheng ZhangAbstract:Recent evidence suggests that Troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, exhibits beneficial effects on diabetes-related symptoms. Here we investigated the effects of Troxerutin on the enhancement of hepatic gluconeogenesis in high-fat diet (HFD)-treated mice and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + Troxerutin group, and Troxerutin group. Troxerutin was treated by daily oral administration at doses of 150 mg/kg/day for 20 weeks. Tauroursodeoxycholic acid (TUDCA) was used to inhibit endoplasmic reticulum stress (ER stress). Our results showed that Troxerutin effectively improved obesity and related metabolic parameters, and liver injuries in HFD-treated mouse. Furthermore, Troxerutin significantly attenuated enhancement of hepatic gluconeogenesis in HFD-fed mouse. Moreover, Troxerutin notably suppressed nuclear factor-κB (NF-κB) p65 transcriptional activation and release of inflammatory cytokines in HFD-treated mouse livers. Mechanismly, Troxerutin dramatically decreased Nucleotide oligomerization domain (NOD) expression, as well as interaction between NOD1/2 with interacting protein-2 (RIP2), by abating oxidative stress-induced ER stress in HFD-treated mouse livers, which was confirmed by TUDCA treatment. These improvement effects of Troxerutin on hepatic glucose disorders might be mediated by its anti-obesity effect. In conclusion, Troxerutin markedly diminished HFD-induced enhancement of hepatic gluconeogenesis via its inhibitory effects on ER stress-mediated NOD activation and consequent inflammation, which might be mediated by its anti-obesity effect.
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Troxerutin protects against 2 2 4 4 tetrabromodiphenyl ether bde 47 induced liver inflammation by attenuating oxidative stress mediated nad depletion
Journal of Hazardous Materials, 2015Co-Authors: Zi-feng Zhang, Shao-hua Fan, Yuan-lin Zheng, Juan Zhuang, Yan-qiu Zhang, Qun ShanAbstract:Emerging evidence indicates that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of Troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD+-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that Troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD+-depletion in BDE-47 treated mice. Consequently, Troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, Troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of Troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that Troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity.
Zi-feng Zhang - One of the best experts on this subject based on the ideXlab platform.
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Troxerutin Protects Kidney Tissue against BDE-47-Induced Inflammatory Damage through CXCR4-TXNIP/NLRP3 Signaling.
Oxidative medicine and cellular longevity, 2018Co-Authors: Qun Shan, Zi-feng Zhang, Gui-hong Zheng, Juan Zhuang, Xin-rui Han, Xin Wen, Shan Wang, Yan-qiu ZhangAbstract:2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) induces oxidative stress in kidney cells, but the underlying mechanism remains poorly understood. Troxerutin, a natural flavonoid, has potential antioxidant and anti-inflammatory efficacy. In this study, we assessed the effect of Troxerutin on kidney damage caused by BDE-47 and investigated the underlying mechanism. The results showed Troxerutin reduced reactive oxygen species (ROS) level and urine albumin-to-creatinine ratio (ACR), decreased the activities of inflammatory factors including cyclooxygenase-2 (COX-2), induced nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) in the kidney tissues of BDE-47-treated mice. Furthermore, Troxerutin significantly weakened the expression of kidney NLRP3 inflammasome containing NLRP3, ASC, and caspase-1, contributing to the decline of IL-1β. Additionally, Troxerutin inhibited the increased protein level of stromal-derived factor-1(SDF-1), C-X-C chemokine ligand 12 receptor 4 (CXCR4), and thioredoxin interaction protein (TXNIP) caused by BDE-47. Specifically, the immunoprecipitation assay indicated that there was a direct interaction between CXCR4 and TXNIP. CXCR4 siRNA and TXNIP siRNA also decreased the inflammatory damage, which was similar to the action of Troxerutin. Our data demonstrated that Troxerutin regulated the inflammatory lesions via CXCR4-TXNIP/NLRP3 inflammasome in the kidney of mice induced by BDE-47.
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Troxerutin protects kidney tissue against bde 47 induced inflammatory damage through cxcr4 txnip nlrp3 signaling
Oxidative Medicine and Cellular Longevity, 2018Co-Authors: Zi-feng Zhang, Gui-hong Zheng, Qun Shan, Juan Zhuang, Yan-qiu Zhang, Xin-rui Han, Xin Wen, Shan Wang, Yuan-lin ZhengAbstract:2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) induces oxidative stress in kidney cells, but the underlying mechanism remains poorly understood. Troxerutin, a natural flavonoid, has potential antioxidant and anti-inflammatory efficacy. In this study, we assessed the effect of Troxerutin on kidney damage caused by BDE-47 and investigated the underlying mechanism. The results showed Troxerutin reduced reactive oxygen species (ROS) level and urine albumin-to-creatinine ratio (ACR), decreased the activities of inflammatory factors including cyclooxygenase-2 (COX-2), induced nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) in the kidney tissues of BDE-47-treated mice. Furthermore, Troxerutin significantly weakened the expression of kidney NLRP3 inflammasome containing NLRP3, ASC, and caspase-1, contributing to the decline of IL-1β. Additionally, Troxerutin inhibited the increased protein level of stromal-derived factor-1(SDF-1), C-X-C chemokine ligand 12 receptor 4 (CXCR4), and thioredoxin interaction protein (TXNIP) caused by BDE-47. Specifically, the immunoprecipitation assay indicated that there was a direct interaction between CXCR4 and TXNIP. CXCR4 siRNA and TXNIP siRNA also decreased the inflammatory damage, which was similar to the action of Troxerutin. Our data demonstrated that Troxerutin regulated the inflammatory lesions via CXCR4-TXNIP/NLRP3 inflammasome in the kidney of mice induced by BDE-47.
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Troxerutin Reduces Kidney Damage against BDE-47-Induced Apoptosis via Inhibiting NOX2 Activity and Increasing Nrf2 Activity.
Oxidative medicine and cellular longevity, 2017Co-Authors: Qun Shan, Zi-feng Zhang, Gui-hong Zheng, Juan Zhuang, Yan-qiu Zhang, Yuan-lin ZhengAbstract:2,2,4,4-Tetrabromodiphenyl ether (BDE-47), one of the persistent organic pollutants, seriously influences the quality of life; however, its pathological mechanism remains unclear. Troxerutin is a flavonoid with pharmacological activity of antioxidation and anti-inflammation. In the present study, we investigated Troxerutin against BDE-47-induced kidney cell apoptosis and explored the underlying mechanism. The results show that Troxerutin reduced renal cell apoptosis and urinary protein secretion in BDE-47-treated mice. Western blot analysis shows that Troxerutin supplement enhanced the ratio of Bcl-2/Bax; inhibited the release of cytochrome c from mitochondria, the activation of procaspase-9 and procaspase-3, and the cleavage of PARP; and reduced FAS, FASL, and caspase-8 levels induced by BDE-47. In addition, Troxerutin decreased the production of reactive oxygen species (ROS) and increased the activities of antioxidative enzymes. Furthermore, Troxerutin blunted Nrf2 ubiquitylation, enhanced the activity of Nrf2, decreased the activity of NOX2, and ameliorated kidney oxidant status of BDE-47-treated mice. Together, these results confirm that Troxerutin could alleviate the cytotoxicity of BDE-47 through antioxidation and antiapoptosis, which suggests that its protective mechanism is involved in the inhibition of apoptosis via suppressing NOX2 activity and increasing Nrf2 signaling pathway.
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Troxerutin Attenuates Enhancement of Hepatic Gluconeogenesis by Inhibiting NOD Activation-Mediated Inflammation in High-Fat Diet-Treated Mice
International journal of molecular sciences, 2016Co-Authors: Zi-feng Zhang, Xin Wang, Gui-hong Zheng, Qun Shan, Shao-hua Fan, Chun-hui Sun, Cheng ZhangAbstract:Recent evidence suggests that Troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, exhibits beneficial effects on diabetes-related symptoms. Here we investigated the effects of Troxerutin on the enhancement of hepatic gluconeogenesis in high-fat diet (HFD)-treated mice and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + Troxerutin group, and Troxerutin group. Troxerutin was treated by daily oral administration at doses of 150 mg/kg/day for 20 weeks. Tauroursodeoxycholic acid (TUDCA) was used to inhibit endoplasmic reticulum stress (ER stress). Our results showed that Troxerutin effectively improved obesity and related metabolic parameters, and liver injuries in HFD-treated mouse. Furthermore, Troxerutin significantly attenuated enhancement of hepatic gluconeogenesis in HFD-fed mouse. Moreover, Troxerutin notably suppressed nuclear factor-κB (NF-κB) p65 transcriptional activation and release of inflammatory cytokines in HFD-treated mouse livers. Mechanismly, Troxerutin dramatically decreased Nucleotide oligomerization domain (NOD) expression, as well as interaction between NOD1/2 with interacting protein-2 (RIP2), by abating oxidative stress-induced ER stress in HFD-treated mouse livers, which was confirmed by TUDCA treatment. These improvement effects of Troxerutin on hepatic glucose disorders might be mediated by its anti-obesity effect. In conclusion, Troxerutin markedly diminished HFD-induced enhancement of hepatic gluconeogenesis via its inhibitory effects on ER stress-mediated NOD activation and consequent inflammation, which might be mediated by its anti-obesity effect.
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Troxerutin protects against 2 2 4 4 tetrabromodiphenyl ether bde 47 induced liver inflammation by attenuating oxidative stress mediated nad depletion
Journal of Hazardous Materials, 2015Co-Authors: Zi-feng Zhang, Shao-hua Fan, Yuan-lin Zheng, Juan Zhuang, Yan-qiu Zhang, Qun ShanAbstract:Emerging evidence indicates that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of Troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD+-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that Troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD+-depletion in BDE-47 treated mice. Consequently, Troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, Troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of Troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that Troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity.
Yuan-lin Zheng - One of the best experts on this subject based on the ideXlab platform.
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Troxerutin protects kidney tissue against bde 47 induced inflammatory damage through cxcr4 txnip nlrp3 signaling
Oxidative Medicine and Cellular Longevity, 2018Co-Authors: Zi-feng Zhang, Gui-hong Zheng, Qun Shan, Juan Zhuang, Yan-qiu Zhang, Xin-rui Han, Xin Wen, Shan Wang, Yuan-lin ZhengAbstract:2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) induces oxidative stress in kidney cells, but the underlying mechanism remains poorly understood. Troxerutin, a natural flavonoid, has potential antioxidant and anti-inflammatory efficacy. In this study, we assessed the effect of Troxerutin on kidney damage caused by BDE-47 and investigated the underlying mechanism. The results showed Troxerutin reduced reactive oxygen species (ROS) level and urine albumin-to-creatinine ratio (ACR), decreased the activities of inflammatory factors including cyclooxygenase-2 (COX-2), induced nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) in the kidney tissues of BDE-47-treated mice. Furthermore, Troxerutin significantly weakened the expression of kidney NLRP3 inflammasome containing NLRP3, ASC, and caspase-1, contributing to the decline of IL-1β. Additionally, Troxerutin inhibited the increased protein level of stromal-derived factor-1(SDF-1), C-X-C chemokine ligand 12 receptor 4 (CXCR4), and thioredoxin interaction protein (TXNIP) caused by BDE-47. Specifically, the immunoprecipitation assay indicated that there was a direct interaction between CXCR4 and TXNIP. CXCR4 siRNA and TXNIP siRNA also decreased the inflammatory damage, which was similar to the action of Troxerutin. Our data demonstrated that Troxerutin regulated the inflammatory lesions via CXCR4-TXNIP/NLRP3 inflammasome in the kidney of mice induced by BDE-47.
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Troxerutin Reduces Kidney Damage against BDE-47-Induced Apoptosis via Inhibiting NOX2 Activity and Increasing Nrf2 Activity.
Oxidative medicine and cellular longevity, 2017Co-Authors: Qun Shan, Zi-feng Zhang, Gui-hong Zheng, Juan Zhuang, Yan-qiu Zhang, Yuan-lin ZhengAbstract:2,2,4,4-Tetrabromodiphenyl ether (BDE-47), one of the persistent organic pollutants, seriously influences the quality of life; however, its pathological mechanism remains unclear. Troxerutin is a flavonoid with pharmacological activity of antioxidation and anti-inflammation. In the present study, we investigated Troxerutin against BDE-47-induced kidney cell apoptosis and explored the underlying mechanism. The results show that Troxerutin reduced renal cell apoptosis and urinary protein secretion in BDE-47-treated mice. Western blot analysis shows that Troxerutin supplement enhanced the ratio of Bcl-2/Bax; inhibited the release of cytochrome c from mitochondria, the activation of procaspase-9 and procaspase-3, and the cleavage of PARP; and reduced FAS, FASL, and caspase-8 levels induced by BDE-47. In addition, Troxerutin decreased the production of reactive oxygen species (ROS) and increased the activities of antioxidative enzymes. Furthermore, Troxerutin blunted Nrf2 ubiquitylation, enhanced the activity of Nrf2, decreased the activity of NOX2, and ameliorated kidney oxidant status of BDE-47-treated mice. Together, these results confirm that Troxerutin could alleviate the cytotoxicity of BDE-47 through antioxidation and antiapoptosis, which suggests that its protective mechanism is involved in the inhibition of apoptosis via suppressing NOX2 activity and increasing Nrf2 signaling pathway.
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Troxerutin protects against 2 2 4 4 tetrabromodiphenyl ether bde 47 induced liver inflammation by attenuating oxidative stress mediated nad depletion
Journal of Hazardous Materials, 2015Co-Authors: Zi-feng Zhang, Shao-hua Fan, Yuan-lin Zheng, Juan Zhuang, Yan-qiu Zhang, Qun ShanAbstract:Emerging evidence indicates that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of Troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD+-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that Troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD+-depletion in BDE-47 treated mice. Consequently, Troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, Troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of Troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that Troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity.
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Troxerutin inhibits 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced hepatocyte apoptosis by restoring proteasome function.
Toxicology letters, 2015Co-Authors: Zi-feng Zhang, Xin Wang, Qun Shan, Shao-hua Fan, Juan Zhuang, Yan-qiu Zhang, Yuan-lin ZhengAbstract:Proteasome dysfunction has been associated with the pathogeneses of a variety of diseases and with the neurotoxicities of environmental chemicals; however, whether proteasome dysfunction plays a role in the cellular toxicity of polybrominated diphenyl ethers (PBDEs) has not been investigated to date. Emerging evidence suggests that antioxidants exhibit evident beneficial effects on the cellular toxicity associated with PBDEs. In the present study, we investigated whether Troxerutin attenuates BDE-47-induced hepatocyte apoptosis by restoring proteasome function and explored the mechanisms underlying this effect. Our results revealed that proteasome dysfunction was involved in the BDE-47-induced hepatocyte apoptosis in the mouse liver. Furthermore, our results revealed that Troxerutin effectively inhibited hepatocyte apoptosis by restoring oxidative stress-mediated proteasome dysfunction in BDE-47-treated mice. Consequently, Troxerutin markedly suppressed endoplasmic reticulum (ER) stress in the livers of the BDE-47-treated mice. The inhibitory effects of Troxerutin on ER stress and apoptotic pathways were markedly blunted by treatment with epoxomicin (a selective inhibitor of proteasome). Ultimately, Troxerutin dramatically blocked TRAF2-ASK1-JNK signaling and CHOP-mediated apoptosis signaling in the BDE-47-treated mouse livers. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that Troxerutin might be a candidate for the prevention of and therapy for BDE-47-induced hepatotoxicity.
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Troxerutin improves hepatic lipid homeostasis by restoring NAD+-depletion-mediated dysfunction of lipin 1 signaling in high-fat diet-treated mice
Biochemical pharmacology, 2014Co-Authors: Zi-feng Zhang, Shao-hua Fan, Yuan-lin Zheng, Qun ShanAbstract:Recent evidences suggest that NAD(+) depletion leads to abnormal hepatic lipid metabolism in high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD); however, the contributing mechanism is not well understood. Our previous study showed that Troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, effectively inhibited obesity, and normalized hyperglycemia and hyperlipidemia in high-cholesterol diet-induced diabetic mice. Here we investigated whether Troxerutin improved hepatic lipid metabolism via preventing NAD(+) depletion in HFD-induced NAFLD mouse model and the mechanisms underlying these effects. Our results showed that Troxerutin markedly prevented obesity, liver steatosis and injury in HFD-fed mice. Troxerutin largely suppressed oxidative stress-mediated NAD(+)-depletion by increasing nicotinamide phosphoribosyltransferase (NAMPT) protein expression and decreasing poly (ADP-ribose) polymerase-1 (PARP1) protein expression and activity in HFD-treated mouse livers. Consequently, Troxerutin remarkably restored Silent mating type information regulation 2 homolog1 (SirT1) protein expression and activity in HFD-treated mouse livers. Therefore, Troxerutin promoted SirT1-mediated AMP-activated protein kinase (AMPK) activation to inhibit mammalian target of rapamycin complex 1 (mTORC1) signaling, which enhanced nuclear lipin 1 localization, lowered cytoplasmic lipin 1 localization and the ratio of hepatic Lpin 1β/α. Ultimately, Troxerutin improved lipid homeostasis by enhancing fatty acid oxidation and triglyceride secretion, and suppressing lipogenesis in HFD-fed mouse livers. In conclusion, Troxerutin displayed beneficial effects on hepatic lipid homeostasis in HFD-induced NAFLD by blocking oxidative stress to restore NAD(+)-depletion-mediated dysfunction of lipin 1 signaling. This study provides novel mechanistic insights into NAFLD pathogenesis and indicates that Troxerutin is a candidate for pharmacological intervention of NAFLD via restoring NAD(+) levels.
Yan-qiu Zhang - One of the best experts on this subject based on the ideXlab platform.
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Troxerutin protects kidney tissue against bde 47 induced inflammatory damage through cxcr4 txnip nlrp3 signaling
Oxidative Medicine and Cellular Longevity, 2018Co-Authors: Zi-feng Zhang, Gui-hong Zheng, Qun Shan, Juan Zhuang, Yan-qiu Zhang, Xin-rui Han, Xin Wen, Shan Wang, Yuan-lin ZhengAbstract:2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) induces oxidative stress in kidney cells, but the underlying mechanism remains poorly understood. Troxerutin, a natural flavonoid, has potential antioxidant and anti-inflammatory efficacy. In this study, we assessed the effect of Troxerutin on kidney damage caused by BDE-47 and investigated the underlying mechanism. The results showed Troxerutin reduced reactive oxygen species (ROS) level and urine albumin-to-creatinine ratio (ACR), decreased the activities of inflammatory factors including cyclooxygenase-2 (COX-2), induced nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) in the kidney tissues of BDE-47-treated mice. Furthermore, Troxerutin significantly weakened the expression of kidney NLRP3 inflammasome containing NLRP3, ASC, and caspase-1, contributing to the decline of IL-1β. Additionally, Troxerutin inhibited the increased protein level of stromal-derived factor-1(SDF-1), C-X-C chemokine ligand 12 receptor 4 (CXCR4), and thioredoxin interaction protein (TXNIP) caused by BDE-47. Specifically, the immunoprecipitation assay indicated that there was a direct interaction between CXCR4 and TXNIP. CXCR4 siRNA and TXNIP siRNA also decreased the inflammatory damage, which was similar to the action of Troxerutin. Our data demonstrated that Troxerutin regulated the inflammatory lesions via CXCR4-TXNIP/NLRP3 inflammasome in the kidney of mice induced by BDE-47.
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Troxerutin Protects Kidney Tissue against BDE-47-Induced Inflammatory Damage through CXCR4-TXNIP/NLRP3 Signaling.
Oxidative medicine and cellular longevity, 2018Co-Authors: Qun Shan, Zi-feng Zhang, Gui-hong Zheng, Juan Zhuang, Xin-rui Han, Xin Wen, Shan Wang, Yan-qiu ZhangAbstract:2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) induces oxidative stress in kidney cells, but the underlying mechanism remains poorly understood. Troxerutin, a natural flavonoid, has potential antioxidant and anti-inflammatory efficacy. In this study, we assessed the effect of Troxerutin on kidney damage caused by BDE-47 and investigated the underlying mechanism. The results showed Troxerutin reduced reactive oxygen species (ROS) level and urine albumin-to-creatinine ratio (ACR), decreased the activities of inflammatory factors including cyclooxygenase-2 (COX-2), induced nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) in the kidney tissues of BDE-47-treated mice. Furthermore, Troxerutin significantly weakened the expression of kidney NLRP3 inflammasome containing NLRP3, ASC, and caspase-1, contributing to the decline of IL-1β. Additionally, Troxerutin inhibited the increased protein level of stromal-derived factor-1(SDF-1), C-X-C chemokine ligand 12 receptor 4 (CXCR4), and thioredoxin interaction protein (TXNIP) caused by BDE-47. Specifically, the immunoprecipitation assay indicated that there was a direct interaction between CXCR4 and TXNIP. CXCR4 siRNA and TXNIP siRNA also decreased the inflammatory damage, which was similar to the action of Troxerutin. Our data demonstrated that Troxerutin regulated the inflammatory lesions via CXCR4-TXNIP/NLRP3 inflammasome in the kidney of mice induced by BDE-47.
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Troxerutin Reduces Kidney Damage against BDE-47-Induced Apoptosis via Inhibiting NOX2 Activity and Increasing Nrf2 Activity.
Oxidative medicine and cellular longevity, 2017Co-Authors: Qun Shan, Zi-feng Zhang, Gui-hong Zheng, Juan Zhuang, Yan-qiu Zhang, Yuan-lin ZhengAbstract:2,2,4,4-Tetrabromodiphenyl ether (BDE-47), one of the persistent organic pollutants, seriously influences the quality of life; however, its pathological mechanism remains unclear. Troxerutin is a flavonoid with pharmacological activity of antioxidation and anti-inflammation. In the present study, we investigated Troxerutin against BDE-47-induced kidney cell apoptosis and explored the underlying mechanism. The results show that Troxerutin reduced renal cell apoptosis and urinary protein secretion in BDE-47-treated mice. Western blot analysis shows that Troxerutin supplement enhanced the ratio of Bcl-2/Bax; inhibited the release of cytochrome c from mitochondria, the activation of procaspase-9 and procaspase-3, and the cleavage of PARP; and reduced FAS, FASL, and caspase-8 levels induced by BDE-47. In addition, Troxerutin decreased the production of reactive oxygen species (ROS) and increased the activities of antioxidative enzymes. Furthermore, Troxerutin blunted Nrf2 ubiquitylation, enhanced the activity of Nrf2, decreased the activity of NOX2, and ameliorated kidney oxidant status of BDE-47-treated mice. Together, these results confirm that Troxerutin could alleviate the cytotoxicity of BDE-47 through antioxidation and antiapoptosis, which suggests that its protective mechanism is involved in the inhibition of apoptosis via suppressing NOX2 activity and increasing Nrf2 signaling pathway.
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Troxerutin protects against 2 2 4 4 tetrabromodiphenyl ether bde 47 induced liver inflammation by attenuating oxidative stress mediated nad depletion
Journal of Hazardous Materials, 2015Co-Authors: Zi-feng Zhang, Shao-hua Fan, Yuan-lin Zheng, Juan Zhuang, Yan-qiu Zhang, Qun ShanAbstract:Emerging evidence indicates that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of Troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD+-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that Troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD+-depletion in BDE-47 treated mice. Consequently, Troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, Troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of Troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that Troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity.
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Troxerutin inhibits 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced hepatocyte apoptosis by restoring proteasome function.
Toxicology letters, 2015Co-Authors: Zi-feng Zhang, Xin Wang, Qun Shan, Shao-hua Fan, Juan Zhuang, Yan-qiu Zhang, Yuan-lin ZhengAbstract:Proteasome dysfunction has been associated with the pathogeneses of a variety of diseases and with the neurotoxicities of environmental chemicals; however, whether proteasome dysfunction plays a role in the cellular toxicity of polybrominated diphenyl ethers (PBDEs) has not been investigated to date. Emerging evidence suggests that antioxidants exhibit evident beneficial effects on the cellular toxicity associated with PBDEs. In the present study, we investigated whether Troxerutin attenuates BDE-47-induced hepatocyte apoptosis by restoring proteasome function and explored the mechanisms underlying this effect. Our results revealed that proteasome dysfunction was involved in the BDE-47-induced hepatocyte apoptosis in the mouse liver. Furthermore, our results revealed that Troxerutin effectively inhibited hepatocyte apoptosis by restoring oxidative stress-mediated proteasome dysfunction in BDE-47-treated mice. Consequently, Troxerutin markedly suppressed endoplasmic reticulum (ER) stress in the livers of the BDE-47-treated mice. The inhibitory effects of Troxerutin on ER stress and apoptotic pathways were markedly blunted by treatment with epoxomicin (a selective inhibitor of proteasome). Ultimately, Troxerutin dramatically blocked TRAF2-ASK1-JNK signaling and CHOP-mediated apoptosis signaling in the BDE-47-treated mouse livers. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that Troxerutin might be a candidate for the prevention of and therapy for BDE-47-induced hepatotoxicity.
Jalal Hassanshahi - One of the best experts on this subject based on the ideXlab platform.
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Ameliorating effect of Troxerutin in unilateral ureteral obstruction induced renal oxidative stress, inflammation, and apoptosis in male rats
Naunyn-Schmiedeberg's Archives of Pharmacology, 2020Co-Authors: Ayat Kaeidi, Zahra Taghipour, Mohammad Allahtavakoli, Iman Fatemi, Elham Hakimizadeh, Jalal HassanshahiAbstract:Unilateral ureteral obstruction (UUO) induces renal injury and Troxerutin attenuates the inflammatory parameters and decreases oxidative stress. Accordingly, this study explored the renoprotective effect of Troxerutin in UUO-induced renal oxidative stress, inflammation, and apoptosis in male Wistar rats. Animals were randomly separated into five groups ( n = 8): control, UUO, and three UUO groups treated with Troxerutin (1, 10, and 100 mg/kg). UUO-induced and vehicle/Troxerutin administration was continued for 3 days. Then serum creatinine, mean arterial pressure (MAP), renal perfusion pressure (RPP), renal vascular resistance (RVR), and renal blood flow (RBF) were measured. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels as some oxidative stress parameters were measured in the left kidney. The immunoblotting method was applied to evaluate the cleaved caspase-3 Bax, Bcl-2, and TNF-α proteins level. The hematoxylin and eosin method was used to assess the kidney tissue damage score (KTDS). In 3 days, UUO significantly increased serum creatinine level, KTDS, RVR, MDA, Bax, cleaved caspase-3, and TNF-α protein levels ( p
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ameliorating effect of Troxerutin in unilateral ureteral obstruction induced renal oxidative stress inflammation and apoptosis in male rats
Naunyn-schmiedebergs Archives of Pharmacology, 2020Co-Authors: Ayat Kaeidi, Zahra Taghipour, Mohammad Allahtavakoli, Iman Fatemi, Elham Hakimizadeh, Jalal HassanshahiAbstract:Unilateral ureteral obstruction (UUO) induces renal injury and Troxerutin attenuates the inflammatory parameters and decreases oxidative stress. Accordingly, this study explored the renoprotective effect of Troxerutin in UUO-induced renal oxidative stress, inflammation, and apoptosis in male Wistar rats. Animals were randomly separated into five groups (n = 8): control, UUO, and three UUO groups treated with Troxerutin (1, 10, and 100 mg/kg). UUO-induced and vehicle/Troxerutin administration was continued for 3 days. Then serum creatinine, mean arterial pressure (MAP), renal perfusion pressure (RPP), renal vascular resistance (RVR), and renal blood flow (RBF) were measured. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels as some oxidative stress parameters were measured in the left kidney. The immunoblotting method was applied to evaluate the cleaved caspase-3 Bax, Bcl-2, and TNF-α proteins level. The hematoxylin and eosin method was used to assess the kidney tissue damage score (KTDS). In 3 days, UUO significantly increased serum creatinine level, KTDS, RVR, MDA, Bax, cleaved caspase-3, and TNF-α protein levels (p < 0.05); and decreased RBF, TAC, SOD, catalase, GPx activity levels and Bcl-2 protein expression level in the left kidney (p < 0.05). Troxerutin (100 mg/kg) significantly attenuates the indicators alteration induced by UUO. Our findings represented that the renoprotective effect of Troxerutin may be related to its anti-oxidative stress, anti-inflammation, anti-apoptosis, and RBF improver properties.