Berberine Ameliorates Doxorubicin-Induced Cardiotoxicity via a SIRT1/p66Shc-Mediated Pathway

Wu, Yongchao; Zhang, Lan; Wu, Zi‐Xiao; Shan, Tong-tong; Xiong, Chen

doi:10.1155/2019/2150394

Cited by 89 publications

(63 citation statements)

References 56 publications

(62 reference statements)

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“…As well as activating SIRT1, BBR is also able to decrease FOXO1 acetylation, triggering anti-apoptotic signaling pathways via Bcl-2 expression, and Bax and caspase-3 downregulation (Yu et al, 2016). A very recent report described the protective effect of BBR against doxorubicin-induced cardiovascular damage (Wu et al, 2019). This effect is mediated by SIRT1/p66Shc pathway (Sampaio et al, 2016).…”

Section: Berberinementioning

confidence: 99%

“…Data obtained in a rat model and in rat H9c2 cardiac cells showed that BBR treatment leads to upregulation of SIRT1 and downregulation of p66shc expression both in vivo and in vitro, resulting in suppression of ROS production, apoptosis, and mitochondrial damage, and improving cardiac dysfunction. This effect did not occur if H9c2 cells were treated with the SIRT1 inhibitor EX-527 (Bai et al, 2018), indicating that BBR action was dependent on SIRT1 (Wu et al, 2019). Another study investigated the beneficial effect of BBR in an in vivo diabetic mouse model and in vitro pancreatic beta cell NIT-1 high glucose treated to induced diabetic condition.…”

Section: Berberinementioning

confidence: 99%

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SIRT1 Activation by Natural Phytochemicals: An Overview

et al. 2020

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Sirtuins are class III histone deacetylases, whose enzymatic activity is dependent on NAD + as a cofactor. Sirtuins are reported to modulate numerous activities by controlling gene expression, DNA repair, metabolism, oxidative stress response, mitochondrial function, and biogenesis. Deregulation of their expression and/or action may lead to tissue-specific degenerative events involved in the development of several human pathologies, including cancer, neurodegeneration, and cardiovascular disease. The most studied member of this class of enzymes is sirtuin 1 (SIRT1), whose expression is associated with increasing insulin sensitivity. SIRT1 has been implicated in both tumorigenic and anticancer processes, and is reported to regulate essential metabolic pathways, suggesting that its activation might be beneficial against disorders of the metabolism. Via regulation of p53 deacetylation and modulation of autophagy, SIRT1 is implicated in cellular response to caloric restriction and lifespan extension. In recent years, scientific interest focusing on the identification of SIRT1 modulators has led to the discovery of novel small molecules targeting SIRT1 activity. This review will examine compounds of natural origin recently found to upregulate SIRT1 activity, such as polyphenolic products in fruits, vegetables, and plants including resveratrol, fisetin, quercetin, and curcumin. We will also discuss the potential therapeutic effects of these natural compounds in the prevention and treatment of human disorders, with particular emphasis on their metabolic impact.

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Section: Berberinementioning

confidence: 99%

Section: Berberinementioning

confidence: 99%

SIRT1 Activation by Natural Phytochemicals: An Overview

et al. 2020

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“…Protection from acute DOX-induced cardiotoxicity [255,[263][264][265][266][267] [288,289] Induced CYP1B1 gene expression [290] Protection from acute DOX-induced cardiotoxicity [291][292][293][294] and chronic DOX-induced cardiotoxicity [295] in vivo Protection from DOX-induced toxicity in H9c2 cells [291,296] and primary rat cardiomyocytes [294] in vitro…”

Section: Chemosensitizing Effects Of Cyp1b1 Inhibitorsmentioning

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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“…In addition to ameliorating cardiac dysfunction, the accumulation in the heart and metabolism of doxorubicin could also be inhibited by berberine. A similar study by Wu et al [68] assessed the doxorubicin-triggered cardiac injury in rats and in cultured cardiac H9c2 cells. The antioxidant mechanism of protection was evident from the increased level of antioxidant enzymes activities (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) and decreased levels of malonaldehyde (MDA) along with improved cardiac activity (electrocardiogram and histopathological changes).…”

Section: Berberine Ameliorates the Toxicity Of Anticancer Drugs In Nomentioning

confidence: 96%

Recent Advances in Berberine Inspired Anticancer Approaches: From Drug Combination to Novel Formulation Technology and Derivatization

Habtemariam

2020

Molecules

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Berberine is multifunctional natural product with potential to treat diverse pathological conditions. Its broad-spectrum anticancer effect through direct effect on cancer cell growth and metastasis have been established both in vitro and in vivo. The cellular targets that account to the anticancer effect of berberine are incredibly large and range from kinases (protein kinase B (Akt), mitogen activated protein kinases (MAPKs), cell cycle checkpoint kinases, etc.) and transcription factors to genes and protein regulators of cell survival, motility and death. The direct effect of berberine in cancer cells is however relatively weak and occur at moderate concentration range (10–100 µM) in most cancer cells. The poor pharmacokinetics profile resulting from poor absorption, efflux by permeability-glycoprotein (P-gc) and extensive metabolism in intestinal and hepatic cells are other dimensions of berberine’s limitation as anticancer agent. This communication addresses the research efforts during the last two decades that were devoted to enhancing the anticancer potential of berberine. Strategies highlighted include using berberine in combination with other chemotherapeutic agents either to reduce toxic side effects or enhance their anticancer effects; the various novel formulation approaches which by order of magnitude improved the pharmacokinetics of berberine; and semisynthetic approaches that enhanced potency by up to 100-fold.

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Berberine Ameliorates Doxorubicin-Induced Cardiotoxicity via a SIRT1/p66Shc-Mediated Pathway

Cited by 89 publications

References 56 publications

SIRT1 Activation by Natural Phytochemicals: An Overview

SIRT1 Activation by Natural Phytochemicals: An Overview

CYP1B1 as a therapeutic target in cardio-oncology

Recent Advances in Berberine Inspired Anticancer Approaches: From Drug Combination to Novel Formulation Technology and Derivatization

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