Flavonoids as detoxifying and pro-survival agents: What's new?

Bjørklund, Geir; Dadar, Maryam; Chirumbolo, Salvatore; Lysiuk, Roman

doi:10.1016/j.fct.2017.10.039

Cited by 35 publications

(19 citation statements)

References 168 publications

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“…Flavonoids have a short half-life (≈2–3 h) and they do not accumulate in the body explaining their low toxicity even when ingested for prolonged periods. Despite this, flavonoids might interfere in the biotransformation of many commonly used drugs such as losartan, digoxin, cyclosporine, vinblastine and fexofenadine by the inhibition of CYP450 enzymes, thus increasing their pharmacological potency (reviewed in [ 232 , 245 ]).…”

Section: Dietary Natural Pigments With Biological Activitymentioning

confidence: 99%

Natural Dietary Pigments: Potential Mediators against Hepatic Damage Induced by Over-The-Counter Non-Steroidal Anti-Inflammatory and Analgesic Drugs

et al. 2018

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Over-the-counter (OTC) analgesics are among the most widely prescribed and purchased drugs around the world. Most analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, are metabolized in the liver. The hepatocytes are responsible for drug metabolism and detoxification. Cytochrome P450 enzymes are phase I enzymes expressed mainly in hepatocytes and they account for ≈75% of the metabolism of clinically used drugs and other xenobiotics. These metabolic reactions eliminate potentially toxic compounds but, paradoxically, also result in the generation of toxic or carcinogenic metabolites. Cumulative or overdoses of OTC analgesic drugs can induce acute liver failure (ALF) either directly or indirectly after their biotransformation. ALF is the result of massive death of hepatocytes induced by oxidative stress. There is an increased interest in the use of natural dietary products as nutritional supplements and/or medications to prevent or cure many diseases. The therapeutic activity of natural products may be associated with their antioxidant capacity, although additional mechanisms may also play a role (e.g., anti-inflammatory actions). Dietary antioxidants such as flavonoids, betalains and carotenoids play a preventive role against OTC analgesics-induced ALF. In this review, we will summarize the pathobiology of OTC analgesic-induced ALF and the use of natural pigments in its prevention and therapy.

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Section: Dietary Natural Pigments With Biological Activitymentioning

confidence: 99%

Natural Dietary Pigments: Potential Mediators against Hepatic Damage Induced by Over-The-Counter Non-Steroidal Anti-Inflammatory and Analgesic Drugs

et al. 2018

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“…It exerts multiple biochemical properties and wide pharmacological effects (Moon, Wang & Morris, 2006). Epidemiological studies have shown that flavonoid is associated with a reduced risk of cardiovascular diseases (Raj Narayana et al, 2001; Bjorklund et al, 2017). Fisetin, a plant-derived bioflavonoid, significantly attenuated I/R-induced tissue injury, blunted the oxidative stress, and restored mitochondrial structure and function (Shanmugam et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Taxifolin protects rat against myocardial ischemia/reperfusion injury by modulating the mitochondrial apoptosis pathway

Tang

Yang

Zuo

et al. 2019

PeerJ

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BackgroundTaxifolin (TAX), is an active flavonoid, that plays an underlying protective role on the cardiovascular system. This study aimed to evaluate its effect and potential mechanisms on myocardial ischemia/reperfusion (I/R) injury.MethodsHealthy rat heart was subjected to I/R using the Langendorff apparatus. Hemodynamic parameters, including heart rate, left ventricular developed pressure (LVDP), maximum/minimum rate of the left ventricular pressure rise (+dp/dtmax and −dp/dtmin) and rate pressure product (RPP) were recorded during the perfusion. Histopathological examination of left ventricular was measured by hematoxylin-eosin (H&E) staining. Creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) activities in the effluent perfusion, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in the tissue were assayed. Apoptosis related proteins, such as B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), and cytochrome c (Cyt-c) were also assayed by ELISA. Western blot was employed to determine apoptosis-executive proteins, including caspase 3 and 9. Transferase-mediated dUTP-X nick end labeling assay was performed to evaluate the effect TAX on myocardial apoptosis.ResultsTaxifolin significantly improved the ventricular functional recovery, as evident by the increase in LVDP, +dp/dtmax, −dp/dtmin and RPP, the levels of SOD, GSH-PX were also increased, but those of LDH, CK-MB, and MDA were decreased. Furthermore, TAX up-regulated the Bcl-2 protein level but down-regulated the levels of Bax, Cyt-c, caspase 3 and 9 protein, thereby inhibits the myocardial apoptosis.DiscussionTaxifolin treatment remarkably improved the cardiac function, regulated oxidative stress and attenuated apoptosis. Hence, TAX has a cardioprotective effect against I/R injury by modulating mitochondrial apoptosis pathway.

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“…Epidemiological studies have indicated that regular consumption of fruits and vegetables containing flavonoids and polyphenols is associated with a reduced risk for the development of cardiovascular diseases, inflammatory diseases, neurodegenerative diseases, and cancer [ 6 ]. The underlying mechanisms of several cardioprotective procedures such as ischemic preconditioning for IRI have been linked to the inhibition of GSK3 β , which provides cardioprotection by modulating mitochondrial ATP-sensitive K + channel, the mammalian target of rapamycin (mTOR) signaling pathway, and autophagy [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Fisetin Confers Cardioprotection against Myocardial Ischemia Reperfusion Injury by Suppressing Mitochondrial Oxidative Stress and Mitochondrial Dysfunction and Inhibiting Glycogen Synthase Kinase 3β Activity

Shanmugam

Ravindran

Kurian

et al. 2018

Oxidative Medicine and Cellular Longevity

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Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide. Timely reperfusion is considered an optimal treatment for AMI. Paradoxically, the procedure of reperfusion can itself cause myocardial tissue injury. Therefore, a strategy to minimize the reperfusion-induced myocardial tissue injury is vital for salvaging the healthy myocardium. Herein, we investigated the cardioprotective effects of fisetin, a natural flavonoid, against ischemia/reperfusion (I/R) injury (IRI) using a Langendorff isolated heart perfusion system. I/R produced significant myocardial tissue injury, which was characterized by elevated levels of lactate dehydrogenase and creatine kinase in the perfusate and decreased indices of hemodynamic parameters. Furthermore, I/R resulted in elevated oxidative stress, uncoupling of the mitochondrial electron transport chain, increased mitochondrial swelling, a decrease of the mitochondrial membrane potential, and induction of apoptosis. Moreover, IRI was associated with a loss of the mitochondrial structure and decreased mitochondrial biogenesis. However, when the animals were pretreated with fisetin, it significantly attenuated the I/R-induced myocardial tissue injury, blunted the oxidative stress, and restored the structure and function of mitochondria. Mechanistically, the fisetin effects were found to be mediated via inhibition of glycogen synthase kinase 3β (GSK3β), which was confirmed by a biochemical assay and molecular docking studies.

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Flavonoids as detoxifying and pro-survival agents: What's new?

Cited by 35 publications

References 168 publications

Natural Dietary Pigments: Potential Mediators against Hepatic Damage Induced by Over-The-Counter Non-Steroidal Anti-Inflammatory and Analgesic Drugs

Natural Dietary Pigments: Potential Mediators against Hepatic Damage Induced by Over-The-Counter Non-Steroidal Anti-Inflammatory and Analgesic Drugs

Taxifolin protects rat against myocardial ischemia/reperfusion injury by modulating the mitochondrial apoptosis pathway

Fisetin Confers Cardioprotection against Myocardial Ischemia Reperfusion Injury by Suppressing Mitochondrial Oxidative Stress and Mitochondrial Dysfunction and Inhibiting Glycogen Synthase Kinase 3β Activity

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