Dietary luteolin attenuates chronic liver injury induced by mercuric chloride via the Nrf2/NF-κB/P53 signaling pathway in rats

Zhang, Haili; Xiao, Tan; Yang, Daqian; Lu, Jingjing; Liu, Biying; Baiyun, Ruiqi; Zhang, Zhigang

doi:10.18632/oncotarget.17334

Cited by 59 publications

(41 citation statements)

References 30 publications

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“…Pre-treatment with LUT significantly improved liver function biomarker levels and indicated that LUT could preserve hepatocyte integrity and relieve liver damage. This is consistent with the findings of Zhang et al [46] and Yang et al [22]. Tai et al [23] reported that LUT treatment improved the disturbance in levels of liver function markers evoked by acetaminophen and that was evident by regeneration of liver cells and healing of damaged hepatic parenchyma.…”

Section: Discussionsupporting

confidence: 91%

Antagonistic Efficacy of Luteolin against Lead Acetate Exposure-Associated with Hepatotoxicity is Mediated via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Activities

et al. 2019

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The abundant use of lead (Pb; toxic heavy metal) worldwide has increased occupational and ecosystem exposure, with subsequent negative health effects. The flavonoid luteolin (LUT) found in many natural foodstuffs possesses antioxidant and anti-inflammatory properties. Herein, we hypothesized that LUT could mitigate liver damage induced by exposure to lead acetate (PbAc). Male Wistar rats were allocated to four groups: control group received normal saline, LUT-treated group (50 mg/kg, oral, daily), PbAc-treated group (20 mg/kg, i.p., daily), and LUT+PbAc-treated group (received the aforementioned doses via the respective routes of administration); the rats were treated for 7 days. The results revealed that PbAc exposure significantly increased hepatic Pb residue and serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin value. Oxidative reactions were observed in the liver tissue following PbAc intoxication, characterized by the depletion and downregulation of antioxidant proteins (glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase, catalase, nuclear factor erythroid 2-related factor 2, and heme oxygenase-1), and an increase in oxidants (malondialdehyde and nitric oxide). Additionally, PbAc increased the release and expression of the pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-1 beta), inducible nitric oxide synthase, and nuclear factor kappa B. Moreover, PbAc enhanced hepatocyte loss by increasing the expression of pro-apoptotic proteins (Bax and caspase-3) and downregulating the anti-apoptotic protein (Bcl-2). The changes in the aforementioned parameters were further confirmed by noticeable histopathological lesions. LUT supplementation significantly reversed all of the tested parameters in comparison with the PbAc-exposed group. In conclusion, our findings describe the potential mechanisms involved in the alleviation of PbAc-induced liver injury by luteolin via its potent anti-inflammatory, antioxidant, and anti-apoptotic properties.

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Section: Discussionsupporting

confidence: 91%

Antagonistic Efficacy of Luteolin against Lead Acetate Exposure-Associated with Hepatotoxicity is Mediated via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Activities

et al. 2019

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“…In addition, Luteolin increased the activity of SOD, CAT and the level of Nrf2 and its downstream targets HO‐1 and NQO1 in 3 % dextran sulfate sodium (DSS)‐treat rats . Besides, Luteolin increased the level of Nrf2 through Nrf2/NF‐ κ B/P53 signaling pathway in the presence of HgCl 2 which led to increased Bax and decreased Bcl‐2 . Furthermore, Luteolin inhibits HgCl 2 ‐induced renal injury by activating Nrf2 signaling pathway and increasing its subsequent protein HO‐1, NQO1 .…”

Section: Natural Polyphenols Nrf2 Activators In Multiple Disease Modelsmentioning

confidence: 99%

“…[56] Besides, Luteolin increased the level of Nrf2 through Nrf2/NF-κB/P53 signaling pathway in the presence of HgCl 2 which led to increased Bax and decreased Bcl-2. [57] Furthermore, Luteolin inhibits HgCl 2 -induced renal injury by activating Nrf2 signaling pathway and increasing its subsequent protein HO-1, NQO1. [58] Tangeretin (19) is a citrus polymethoxylated flavonoid that has been shown to have a wide range of pharmacological properties.…”

Section: Flavonementioning

confidence: 99%

Recent Advances of Natural Polyphenols Activators for Keap1‐Nrf2 Signaling Pathway

Zhou

Jiang

et al. 2019

Chemistry & Biodiversity

149

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The Keap1‐Nrf2/ARE signaling pathway is an important defense system against exogenous and endogenous oxidative stress injury. The dysregulation of the signaling pathway is associated with many diseases, such as cancer, diabetes, and respiratory diseases. Over the years, a wide range of natural products has provided sufficient resources for the discovery of potential therapeutic drugs. Among them, polyphenols possess Nrf2 activation, not only inhibit the production of ROS, inhibit Keap1‐Nrf2 protein–protein interaction, but also degrade Keap1 and regulate the Nrf2 related pathway. In fact, with the continuous improvement of natural polyphenols separation and purification technology and further studies on the Keap1‐Nrf2 molecular mechanism, more and more natural polyphenols monomer components of Nrf2 activators have been gradually discovered. In this view, we summarize the research status of natural polyphenols that have been found with apparent Nrf2 activation and their action modes. On the whole, this review may guide the design of novel Keap1‐Nrf2 activator.

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“…Gadacha et al have reported that resveratrol acts as an antioxidant during the active phase and as a pro-oxidant during the inactive phase of rats [46], suggesting certain polyphenols have different effects depending on the intake timing. Several reports have revealed that high concentration of luteolin (80-100 mg/ kg) attenuates the liver injury and hepatotoxicity through the activation of Nrf2 [21,22]. Taken together, these results suggest that luteolin intake at the start of active phase may possess the powerful effect for prevention and amelioration to several diseases occurring from oxidative stress through the activation of Nrf2 even if the amount of luteolin is very low.…”

Section: Plos Onementioning

confidence: 67%

“…The serum concentration of luteolin reaches about 100 nM by dietary habit [19]. Luteolin possesses a lot of physiological functions including antioxidative activity [21,22], while the number of cultured cells and animal studies evaluate the effects in the concentration that exceeds the amount taken from the daily meal. On the other hand, our previous study revealed that the physiological nanomolarconcentration range of luteolin induces Nrf2/ARE pathway in human hepatoma HepG2 cells [23].…”

mentioning

confidence: 99%

Low dose of luteolin activates Nrf2 in the liver of mice at start of the active phase but not that of the inactive phase

et al. 2020

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A flavone luteolin has various health-promoting activities. Several studies reported that high dose of luteolin activates the Nrf2/ARE pathway in the liver. However, the effect of the low dose of luteolin that can be taken from a dietary meal on the Nrf2 activation remain unclear. It is expected that the flavonoid metabolism possesses a circadian rhythm, since nutritional metabolism processes daily cycle. In this study we investigated whether an administration affects the Nrf2 activation. ICR mice were orally administered 0.01-10 mg/kg body weight of luteolin once a day for 7 days at two time-points: at the start of active phase (ZT12) or at that of inactive phase (ZT0). Luteolin increased the nuclear translocation of Nrf2, resulting in the increases in its target gene products HO-1 and NQO1 at ZT12 but not at ZT0. The expression level of Nrf2 was lower at ZT12 than at ZT0 in the liver. We also found that the level of luteolin aglycon in the plasma is higher at ZT12 than at ZT0. These results suggest that the low dose of luteolin can activate Nrf2 pathway and the aglycon form of luteolin may mainly contribute to activate the Nrf2 pathway at ZT12 in the liver. OPEN ACCESSCitation: Kitakaze T, Makiyama A, Yamashita Y, Ashida H (2020) Low dose of luteolin activates Nrf2 in the liver of mice at start of the active phase but not that of the inactive phase. PLoS ONE 15(4): e0231403. https://doi.org/10.beneficial functions for human health. However, most of study have not considered feeding time of flavonoids. Thus, the involvement of feeding time on the function of flavonoids remain unclear.Flavonoids possess various health-promoting activities as antioxidants. Evidences from the cultured cells and animal studies revealed that individual flavonoids have many health benefits, such as prevention of oxidative stress, inflammation and lipid accumulation [5,6]. Epidemiological studies suggest that high dietary intake of flavonoids is associated with lower risk of diseases including cardiovascular disease and several types of cancer [7,8]. The mean daily intake of flavonoids has been estimated in many countries; e.g., US (207.0 mg/day), Korea (318.0 mg/ day) and Spain (376.69 mg/day) [9][10][11]. A number of animal studies are intended to evaluate the effects of high dose of flavonoids (more than 10 mg/kg), but little is known about the function of low dose of flavonoids that can be taken from a dietary meal.Many flavonoids have antioxidant activity not only by its free radical scavenging ability but also by inducing the expression of antioxidant enzymes. Nuclear factor-erythroid-2-related factor 2 (Nrf2) belongs to the cap'n'collar basic leucine zipper family, and is a key regulator of oxidative stress in numerous types of cells, as well as hepatocytes. Nrf2 is primarily regulated by Kelch-like ECH-associated protein 1 (Keap1), a substrate adaptor for a cul3-containing E3 ubiquitin ligase [12]. Under the normal condition, Nrf2 interacts with Keap1 in the cytoplasm and is rapidly degraded by the ubiquitin-proteasome pathway ...

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Dietary luteolin attenuates chronic liver injury induced by mercuric chloride via the Nrf2/NF-κB/P53 signaling pathway in rats

Cited by 59 publications

References 30 publications

Antagonistic Efficacy of Luteolin against Lead Acetate Exposure-Associated with Hepatotoxicity is Mediated via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Activities

Antagonistic Efficacy of Luteolin against Lead Acetate Exposure-Associated with Hepatotoxicity is Mediated via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Activities

Recent Advances of Natural Polyphenols Activators for Keap1‐Nrf2 Signaling Pathway

Low dose of luteolin activates Nrf2 in the liver of mice at start of the active phase but not that of the inactive phase

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