Celastrol ameliorates cisplatin nephrotoxicity by inhibiting NF-κB and improving mitochondrial function

Yu, Xiaowen; Meng, Xia; Xu, Man; Zhang, Xuejuan; Zhang, Yue; Ding, Guofu; Huang, Songming; Zhang, Aihua; Jia, Zhanjun

doi:10.1016/j.ebiom.2018.09.031

Cited by 149 publications

(105 citation statements)

References 41 publications

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“…NF‐κB activation in the cisplatin‐administered rat's kidneys is a direct consequence of the increased generation of ROS. Numerous studies have established an inflammatory response being next to cisplatin administration in experimental animals . Few research studies have reported the role of elevated expression of NF‐κB in nephrotoxicity in humans and experimental animals .…”

Section: Discussionmentioning

confidence: 99%

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Qin¹,

Meghana²,

Sowjanya³

et al. 2019

BioFactors

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In kidneys, elevated levels of inflammatory cytokines and oxidative stress were observed in nephrotoxicity triggered by cisplatin. Embelin has the anti-inflammatory property. It also got anti-tumorigenic and antioxidant properties. In this research, we analyzed the actions of embelin on nephrotoxicity triggered by cisplatin and vital actions by which it increases antioxidant actions and corrects the inflammation after embelin administration during nephrotoxicity triggered by cisplatin. Kidney function markers including blood urea nitrogen; serum creatinine; the markers of oxidative stress like malondialdehyde (MDA), antioxidant systems like glutathione, superoxide dismutase, glutathione S-transferase, catalase, and glutathione reductase; inflammation markers like nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1 beta (IL-1β); and the extent of nuclear factor-erythroid-2 p45-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) were determined. Histopathology studies of kidneys were also used to analyze nephrotoxicity induced by cisplatin. Treatment with embelin (25 and 50 mg/kg) upgrades the function of kidneys, by elevating antioxidant levels and reducing the MDA level in cisplatin-administered rats. Embelin treatment demonstrated a significant curtailment of oxidative stress as well as increased the activities of antioxidant enzymes, endogenously. Cisplatin upregulates cytokines (i.e., TNF-α and IL-1β) and NF-κB, and downregulates Nrf2 and HO-1. Embelin treatment also reduced the infiltration of neutrophils in the renal tubules and thus reduced the level of histological impairment. The outcome of this study implements that the signaling pathway of Nrf2/HO-1 may be the principal mechanism of embelin for protection from nephrotoxicity triggered by cisplatin, and thus, embelin diminishes oxidative stress and inflammation by impeding NF-κB.

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Section: Discussionmentioning

confidence: 99%

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Qin¹,

Meghana²,

Sowjanya³

et al. 2019

BioFactors

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“…Celastrol possesses multiple pharmacological effects and showed potent anti-inflammatory effect against many disease models, [10][11][12][13] and however, few reports can be seen regarding the anti-inflammatory potential of celastrol in liver fibrosis. SIR2 is a family of histone deacetylases and is widely distributed in cells with multiple functions.…”

Section: The Active Ingredients Extracted From Traditional Chinesementioning

confidence: 99%

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Wang

et al. 2019

J Cellular Molecular Medi

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Celastrol, a pentacyclic tritepene extracted from Tripterygium Wilfordi plant, showing potent liver protection effects on several liver‐related diseases. However, the anti‐inflammatory potential of celastrol in liver fibrosis and the detailed mechanisms remain uncovered. This study was to investigate the anti‐inflammatory effect of celastrol in liver fibrosis and to further reveal mechanisms of celastrol‐induced anti‐inflammatory effects with a focus on AMPK‐SIRT3 signalling. Celastrol showed potent ameliorative effects on liver fibrosis both in activated hepatic stellate cells (HSCs) and in fibrotic liver. Celastrol remarkably suppressed inflammation in vivo and inhibited the secretion of inflammatory factors in vitro. Interestingly, celastrol increased SIRT3 promoter activity and SIRT3 expression both in fibrotic liver and in activated HSCs. Furthermore, SIRT3 silencing evidently ameliorated the anti‐inflammatory potential of celastrol. Besides, we found that celastrol could increase the AMPK phosphorylation. Further investigation showed that SIRT3 siRNA decreased SIRT3 expression but had no obvious effect on phosphorylation of AMPK. In addition, inhibition of AMPK by employing compound C (an AMPK inhibitor) or AMPK1α siRNA significantly suppressed SIRT3 expression, suggesting that AMPK was an up‐stream protein of SIRT3 in liver fibrosis. We further found that depletion of AMPK significantly attenuated the inhibitory effect of celastrol on inflammation. Collectively, celastrol attenuated liver fibrosis mainly through inhibition of inflammation by activating AMPK‐SIRT3 signalling, which makes celastrol be a potential candidate compound in treating or protecting against liver fibrosis.

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“…Panaxynol treatment reduced the serum creatinine and BUN in mice with cisplatin-induced kidney injury. Several reports have indicated that various inflammatory factors such as TNF-α, IL-6, MCP-1, and COX-2 are upregulated in cisplatin-induced nephrotoxicity in both humans and rodents [40,41]. The panaxynol-treated group exhibited significantly decreased COX-2 mRNA expression and slightly decreased MCP-1 mRNA expression in the kidneys compared to the cisplatin alone group.…”

Section: Discussionmentioning

confidence: 94%

Protective Effect of Panaxynol Isolated from Panax vietnamensis against Cisplatin-Induced Renal Damage: In Vitro and In Vivo Studies

Lee

Vu-Huynh

et al. 2019

Biomolecules

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Polyacetylenic compounds isolated from Panax species are comprised of non-polar C17 compounds, exhibiting anti-inflammatory, antitumor, and antifungal activities. Panaxynol represents the major component of the essential oils of ginseng. We investigated whether panaxynol isolated from Panax vietnamensis (Vietnamese ginseng, VG) could prevent cisplatin-induced renal damage induced in vitro and in vivo. Cisplatin-induced apoptotic cell death was observed by staining with annexin V conjugated with Alexa Fluor 488, and western blotting evaluated the molecular mechanism. Panaxynol at concentrations above 0.25 μM prevented cisplatin-induced LLC-PK1 porcine renal proximal tubular cell death. LLC-PK1 cells treated with cisplatin demonstrated an increase in apoptotic cell death, whereas pretreatment with 2 and 4 μM panaxynol decreased this effect. Cisplatin demonstrated a marked increase in the phosphorylation of c-Jun N-terminal kinase (JNK), P38, and cleaved caspase-3. However, pretreatment with 2 and 4 μM panaxynol reversed the upregulated phosphorylation of JNK, P38, and the expression of cleaved caspase-3. We confirmed that the protective effect of panaxynol isolated from P. vietnamensis in LLC-PK1 cells was at least partially mediated by reducing the cisplatin-induced apoptotic damage. In the animal study, panaxynol treatment ameliorated body weight loss and blood renal function markers and downregulated the mRNA expression of inflammatory mediators.

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Celastrol ameliorates cisplatin nephrotoxicity by inhibiting NF-κB and improving mitochondrial function

Cited by 149 publications

References 41 publications

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Protective Effect of Panaxynol Isolated from Panax vietnamensis against Cisplatin-Induced Renal Damage: In Vitro and In Vivo Studies

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