Kaempferol ameliorates Cisplatin induced nephrotoxicity by modulating oxidative stress, inflammation and apoptosis via ERK and NF-κB pathways

Wang, Zhu; Sun, Wenli; Sun, Xi; Wang, Ye; Zhou, Mi

doi:10.1186/s13568-020-00993-w

Cited by 87 publications

(65 citation statements)

References 39 publications

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“…For instance, chrysin offers protection against cisplatin-induced hepatotoxicity and colon toxicity [340]. Luteolin, kaempferol, chrysin, and quercetin also prevent ototoxicity and nephrotoxicity damage induced by cisplatin [340][341][342][343][344][345]. Resveratrol offered protection against cisplatin-induced epididymal toxicity, testicular toxicity, and toxicity in ovarian and cavity cancer cells [346,347].…”

Section: Other Cardiotoxic Cancer Treatments Cisplatinmentioning

confidence: 99%

CYP1B1 as a therapeutic target in cardio-oncology

2020

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Cardiovascular complications have been frequently reported in cancer patients and survivors, mainly because of various cardiotoxic cancer treatments. Despite the known cardiovascular toxic effects of these treatments, they are still clinically used because of their effectiveness as anti-cancer agents. In this review, we discuss the growing body of evidence suggesting that inhibition of the cytochrome P450 1B1 enzyme (CYP1B1) can be a promising therapeutic strategy that has the potential to prevent cancer treatment-induced cardiovascular complications without reducing their anti-cancer effects. CYP1B1 is an extrahepatic enzyme that is expressed in cardiovascular tissues and overexpressed in different types of cancers. A growing body of evidence is demonstrating a detrimental role of CYP1B1 in both cardiovascular diseases and cancer, via perturbed metabolism of endogenous compounds, production of carcinogenic metabolites, DNA adduct formation, and generation of reactive oxygen species (ROS). Several chemotherapeutic agents have been shown to induce CYP1B1 in cardiovascular and cancer cells, possibly via activating the Aryl hydrocarbon Receptor (AhR), ROS generation, and inflammatory cytokines. Induction of CYP1B1 is detrimental in many ways. First, it can induce or exacerbate cancer treatment-induced cardiovascular complications. Second, it may lead to significant chemo/radio-resistance, undermining both the safety and effectiveness of cancer treatments. Therefore, numerous preclinical studies demonstrate that inhibition of CYP1B1 protects against chemotherapy-induced cardiotoxicity and prevents chemo- and radio-resistance. Most of these studies have utilized phytochemicals to inhibit CYP1B1. Since phytochemicals have multiple targets, future studies are needed to discern the specific contribution of CYP1B1 to the cardioprotective and chemo/radio-sensitizing effects of these phytochemicals.

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Section: Other Cardiotoxic Cancer Treatments Cisplatinmentioning

confidence: 99%

CYP1B1 as a therapeutic target in cardio-oncology

2020

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“…NF-κB is present in the cytoplasm along with IκBα, an inhibitory protein. Previous research has demonstrated that NF-κB is activated by the phosphorylation of IκBα, thereby triggering the expression of genes associated with inflammation ( Wang et al., 2020 ). The activation of NF-κB subsequently induces the expression of proinflammatory cytokines, including nitric oxide synthase (iNOS), COX-2, tumor necrosis factor (TNF-α), interleukin 1 beta (IL-1β), and interleukin-6 (IL-6) ( Rojas et al., 2013 ; Liang et al., 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Kaempferol Protects Blood Vessels From Damage Induced by Oxidative Stress and Inflammation in Association With the Nrf2/HO-1 Signaling Pathway

et al. 2020

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Over recent years, an increasing number of studies have confirmed that the occurrence and development of vascular pathological changes are closely related to oxidative stress and the inflammatory response of the vascular endothelium. Kaempferol is the most common flavonoid compound found in fruits and vegetables. Our present research identified that kaempferol had the capability to protect the vascular endothelium in a mouse model of vascular injury and explored the specific mechanisms underlying these effects by investigating oxidative stress, the extent of cardiovascular injury, and inflammatory markers such as NF-kB, TNF-a, IL-6, and the Nrf2/HO-1 signaling pathway. Analysis showed that kaempferol reduced oxidative stress and inflammation mediated by H 2 O 2 and paraquat, respectively, both in vitro and in vivo. Furthermore, kaempferol suppressed the levels of TNF-a and IL-6, and the activation of NF-kB, in aortic tissues and human umbilical vein endothelial cells (HUVECs). Finally, we observed that kaempferol corrected the levels of antioxidants and elevated the protein levels of Nrf2 and HO-1 in aortic tissues and HUVECs. Collectively, our findings prove that kaempferol protects blood vessels from damage induced by oxidative stress and inflammation and that the Nrf2/HO-1 signaling pathway plays a key role in mediating these effects.

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“…Kaempferol can treat cholangiocarcinoma through the PI3K-AKT pathway [24] . Moreover, kaempferol lowers the levels of TP53, which is involved in attenuating apoptosis mediated by Cisplatin [52] . In terms of beta-sitosterol, it is reported to induce MAPK phosphorylation, downregulate the PI3K/Akt, thus promote cell apoptosis and cell death [53] .…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology Based Research into the Effect and Mechanism of Yinchenhao Decoction Against Cholangiocarcinoma

Chen

Lin

Liao

et al. 2020

Preprint

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Background: This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. Methods: By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. Results: 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. Conclusion: As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effects through multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.

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Kaempferol ameliorates Cisplatin induced nephrotoxicity by modulating oxidative stress, inflammation and apoptosis via ERK and NF-κB pathways

Cited by 87 publications

References 39 publications

CYP1B1 as a therapeutic target in cardio-oncology

CYP1B1 as a therapeutic target in cardio-oncology

Kaempferol Protects Blood Vessels From Damage Induced by Oxidative Stress and Inflammation in Association With the Nrf2/HO-1 Signaling Pathway

Network Pharmacology Based Research into the Effect and Mechanism of Yinchenhao Decoction Against Cholangiocarcinoma

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