Paeonol prevents IL-1β-induced inflammatory response and degradation of type II collagen in human primary chondrocytes

Wang, Qianjun; Xu, Xiaomei; Kang, Zhiqiang; Zhang, Zhentao; Li, Yanmin

doi:10.1080/21691401.2019.1613418

Cited by 17 publications

(10 citation statements)

References 38 publications

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“…The results of the present study have shown that paeonol prevents MTX-induced NOX-2 increase. In agreement with these results, paeonol decreased NOX-2 in rat primary microglia [39] and human primary chondrocytes [40]. In the current study, the ability of paeonol to significantly improve cardiac GSH level and SOD activity along with a decrease in MDA level is consistent with the finding of Li et al [41] who reported that paeonol significantly increased cardiac GSH level and SOD activity besides decreasing MDA level in isoproterenol-induced myocardial injury in rats.…”

Section: Discussionsupporting

confidence: 92%

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

Al‐Taher

Morsy

Rifaai

et al. 2020

Mediators of Inflammation

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Methotrexate (MTX) is a commonly used chemotherapeutic agent. Oxidative stress and inflammation have been proved in the development of MTX toxicity. Paeonol is a natural phenolic compound with various pharmacological activities including antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the protective effect of paeonol against MTX-induced cardiac toxicity in rats and to evaluate the various mechanisms that underlie this effect. Paeonol (100 mg/kg) was administered orally for 10 days. MTX cardiac toxicity was induced at the end of the fifth day of the experiment, with or without paeonol pretreatment. MTX-induced cardiac damage is evidenced by a distortion in the normal cardiac histological structure, with significant oxidative and nitrosative stress shown as a significant increase in NADPH oxidase-2, malondialdehyde, and nitric oxide levels along with a decrease in reduced glutathione concentration and superoxide dismutase activity compared to the control group. MTX-induced inflammatory effects are evidenced by the increased cardiac toll-like receptor 4 (TLR4) mRNA expression and protein level as well as increased cardiac tumor necrosis factor- (TNF-) α and interleukin- (IL-) 6 levels along with increased nuclear factor- (NF-) κB/p65 immunostaining. MTX increased apoptosis as shown by the upregulation of cardiac caspase 3 immunostaining. Paeonol was able to correct the oxidative and nitrosative stress as well as the inflammatory and apoptotic parameters and restore the normal histological structure compared to MTX alone. In conclusion, paeonol has a protective effect against MTX-induced cardiac toxicity through inhibiting oxidative and nitrosative stress and suppressing the TLR4/NF-κB/TNF-α/IL-6 inflammatory pathway, as well as causing an associated reduction in the proapoptotic marker, caspase 3.

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Section: Discussionsupporting

confidence: 92%

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

Al‐Taher

Morsy

Rifaai

et al. 2020

Mediators of Inflammation

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“…Therefore, 100 μmol/L of Pae was considered to be the safest concentration. In light of the results from previous studies [ 26 , 27 ], this concentration was used to explore the effects of Pae on mitochondrial homeostasis including mitochondrial dynamics and biogenesis in primary cardiomyocytes. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Paeonol promotes Opa1-mediated mitochondrial fusion via activating the CK2α-Stat3 pathway in diabetic cardiomyopathy

Liu

Han

et al. 2021

Redox Biology

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Diabetes disrupts mitochondrial function and often results in diabetic cardiomyopathy (DCM). Paeonol is a bioactive compound that has been reported to have pharmacological potential for cardiac and mitochondrial protection. This study aims to explore the effects of paeonol on mitochondrial disorderes in DCM and the underlying mechanisms. We showed that paeonol promoted Opa1-mediated mitochondrial fusion, inhibited mitochondrial oxidative stress, and preserved mitochondrial respiratory capacity and cardiac performance in DCM in vivo and in vitro . Knockdown of Opa1 blunted the above protective effects of paeonol in both diabetic hearts and high glucose-treated cardiomyocytes. Mechanistically, inhibitor screening, siRNA knockdown and chromatin immunoprecipitation experiments showed that paeonol-promoted Opa1-mediated mitochondrial fusion required the activation of Stat3, which directly bound to the promoter of Opa1 to upregulate its transcriptional expression. Moreover, pharmmapper screening and molecular docking studies revealed that CK2α served as a direct target of paeonol that interacted with Jak2 and induced the phosphorylation and activation of Jak2-Stat3. Knockdown of CK2α blunted the promoting effect of paeonol on Jak2-Stat3 phosphorylation and Opa1-mediated mitochondrial fusion. Collectively, we have demonstrated for the first time that paeonol is a novel mitochondrial fusion promoter in protecting against hyperglycemia-induced mitochondrial oxidative injury and DCM at least partially via an Opa1-mediated mechanism, a process in which paeonol interacts with CK2α and restores its kinase activity that subsequently increasing Jak2-Stat3 phosphorylation and enhancing the transcriptional level of Opa1. These findings suggest that paeonol or the promotion of mitochondrial fusion might be a promising strategy for the treatment of DCM.

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“…Paeonol displayed the same anti‐inflammatory effects in monosodium urate‐induced arthritis in rats (Chen et al, 2019) and lipopolysaccharides‐induced acute lung injury in mice (Wang, Zhu, et al, 2019). Moreover, paeonol protected against endoplasmic reticulum stress‐associated inflammation in lead‐stimulated kidneys (Liu et al, 2018) and IL‐1β‐induced inflammatory response in human primary chondrocytes (Wang, Xu, Kang, Zhang, & Li, 2019).…”

Section: Discussionmentioning

confidence: 99%

Paeonol protects against testicular ischaemia‐reperfusion injury in rats through inhibition of oxidative stress and inflammation

et al. 2020

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Ischaemia‐reperfusion (IR) is the most common form of testicular injury that results in oxidative damage and inflammation ending by subinfertility. Paeonol, a natural phenolic compound, exhibits antioxidant and anti‐inflammatory effects. Thus, the present study investigated the role of paeonol in rat testicular IR injury. Thirty adult Wistar rats were randomly divided into five groups; sham, sham treated with paeonol, IR injury, and IR pre‐treated with paeonol at low and high doses. Serum testosterone and testicular levels of malondialdehyde and reduced glutathione (GSH) besides superoxide dismutase (SOD) activity were determined. Gene quantifications for tumour necrosis factor‐α (TNF‐α), hypoxia‐inducible factor‐1α (HIF‐1α) and heat shock protein 70 (HSP70) were also assessed. Histopathological pictures and the immunohistochemical expression of testicular nuclear factor erythroid 2‐related factor 2 (Nrf2), interleukin‐1β (IL‐1β) and interleukin‐6 (IL‐6) were shown. Pre‐treatment with paeonol prevented the drop in serum testosterone, alongside with improvement of testicular malondialdehyde and GSH levels plus SOD activity. Paeonol regained the normal spermatogenesis with prevention of IR‐induced increase in TNF‐α, HIF‐1α and HSP70 gene expression besides IL‐1β and IL‐6 immunostaining and reduction in Nrf2 protein expression. Paeonol exerted a dose‐dependent beneficial effect on testicular IR injury. This effect was achieved by its antioxidant and anti‐inflammatory effects.

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Paeonol prevents IL-1β-induced inflammatory response and degradation of type II collagen in human primary chondrocytes

Cited by 17 publications

References 38 publications

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

Paeonol promotes Opa1-mediated mitochondrial fusion via activating the CK2α-Stat3 pathway in diabetic cardiomyopathy

Paeonol protects against testicular ischaemia‐reperfusion injury in rats through inhibition of oxidative stress and inflammation

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