Kaempferol protects mitochondria and alleviates damages against endotheliotoxicity induced by doxorubicin

Wu, Weiqi; Yang, Bin; Qiao, Yi; Zhou, Qing; He, Huan; He, Ming

doi:10.1016/j.biopha.2020.110040

Cited by 35 publications

(19 citation statements)

References 35 publications

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“…In brief, although Kae can effectively relieve oxidative damage and inflammation in a variety of organs, only a small number of studies have confirmed its effect on vascular damage. Recent studies have shown that Kae can reduce doxorubicin-induced endothelial toxicity injury, and that this protective effect is related to the inhibition of oxidative stress ( Wu et al., 2020 ). However, it is unclear whether Kae can protect against vascular damage induced by other pro-oxidative factors.…”

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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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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“…In addition, doxorubicin quinone-containing structure is prone to ROS release by redox-cycling reaction that, associated to a reduction in endogenous antioxidants, increase oxidative stress, ultimately leading to myocyte apoptosis [27]. Among several strategies to limit doxorubicin adverse effects, natural polyphenolic compounds are notable as a cardioprotective agent because of the low toxicity and good antioxidant properties through radical-scavenging activity, carbonyl reductase-inhibitory effects, as well as, modulation of endogenous antioxidant enzymes [28][29][30][31]. Apart from their antioxidant effects, also apoptosis modulation is involved in the protective properties of the flavonoids against doxorubicin toxicity [32].…”

Section: Discussionmentioning

confidence: 99%

Citrus sinensis and Vitis vinifera Protect Cardiomyocytes from Doxorubicin-Induced Oxidative Stress: Evaluation of Onconutraceutical Potential of Vegetable Smoothies

et al. 2020

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The interest towards nutraceuticals able to counteract drug side effects is continuously growing in current chemotherapeutic protocols. In the present study, we demonstrated that smoothies containing mixtures of Citrus sinensis and Vitis vinifera L. cv. Aglianico N, two typical fruits of the Mediterranean diet, possess bioactive polyphenols that protect cardiomyocytes against doxorubicin-induced oxidative stress. The polyphenolic extracts isolated from Citrus sinensis- and Vitis vinifera-based functional smoothies were deeply characterized by Liquid Chromatography-Mass Spectrometry methods. Subsequently, the functional smoothies and relative mixtures were tested to verify their ability to affect cellular viability and oxidative stress parameters in embryonic cardiomyocyte cells (H9c2), and human breast adenocarcinoma cell line (MCF-7) exposed to doxorubicin. Interestingly, we found that the mix resulting from Citrus sinensis and Vitis vinifera association in ratio 1:1 was able to reduce cardiomyocytes damage induced by anthracyclines, without significantly interfering with the pro-apoptotic activity of the drug on breast cancer cells. These results point out the potential use of vegetable smoothies as adjuvants functional foods for chemotherapeutic anticancer protocols.

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“…Several flavonoids activate eNOS in a Ca 2+ -independent manner through the induction of Ser-1179 phosphorylation and/or Thr-495 dephosphorylation [e.g., epigallocatechin gallate (39), quercetin (40), luteolin (41), hesperetin (42), hesperidin and naringin (43)] or through a Ca 2+dependent mechanism [e.g., quercetin (44) and (-)-epicatechin (45)]. Furthermore, flavonoids down-regulate caveloin-1 (a negative regulator of eNOS) expression or dissociate it from eNOS (45,46), activate the chaperone protein HSP90 that is involved in eNOS activation (47), reduce the level of the eNOS inhibitor asymmetrical dimethylarginine (48,49), or inhibit arginase to increase the level of the eNOS substrate arginine (50,51), thus stimulating eNOS activity, and enhancing NO production. Moreover, quercetin, naringenin, and fisetin activate sirtuin-1 that, in turn, deacetylates eNOS, thus improving endothelial function (52).…”

Section: Flavonoids Protect Against Endothelial Dysfunctionmentioning

confidence: 99%

Flavonoids and cardiovascular risk factors: a review

Alayoud¹

2021

Pharm Adv

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Kaempferol protects mitochondria and alleviates damages against endotheliotoxicity induced by doxorubicin

Cited by 35 publications

References 35 publications

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

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

Citrus sinensis and Vitis vinifera Protect Cardiomyocytes from Doxorubicin-Induced Oxidative Stress: Evaluation of Onconutraceutical Potential of Vegetable Smoothies

Flavonoids and cardiovascular risk factors: a review

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