Luteolin-mediated PI3K/AKT/Nrf2 signaling pathway ameliorates inorganic mercury-induced cardiac injury

Baiyun, Ruiqi; Li, Siyu; Liu, Biying; Lu, Jingjing; Lv, Yueying; Xu, Jun; Wu, Jiahui; Li, Jiayi; Lv, Zhanjun; Zhang, Zhigang

doi:10.1016/j.ecoenv.2018.06.046

Cited by 72 publications

(38 citation statements)

References 43 publications

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“…Increasing evidence has demonstrated that luteolin has a certain therapeutic effect on cardiovascular disease, including preventing ischemia/reperfusion injury in adult rats (14) and sodium fluoride-induced hypertension in rats (28), ameliorating inorganic mercury-induced cardiac injury in rats (29), decreasing high-carbohydrate/high-fat diet-induced myocardial inflammation (15), and improving angiotensin II-induced cardiac remodeling by decreasing oxidative stress (16). SIc, first described by Parker et al (30) in 1984, is a complication of severe sepsis and septic shock characterized by an invertible myocardial depression.…”

Section: Discussionmentioning

confidence: 99%

Luteolin attenuates sepsis‑induced myocardial�injury by enhancing autophagy in mice

Song

Fan

et al. 2020

Int J Mol Med

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Sepsis-induced cardiomyopathy (SIc) is a complication of severe sepsis and septic shock characterized by an invertible myocardial depression. This study sought to explore the potential effects and mechanism of luteolin, a flavonoid polyphenolic compound, in lipopolysaccharide (LPS)-induced myocardial injury. Experimental mice were randomly allocated into 3 groups (25 mice in each group): The control group (Nc), the LPS group (LPS) and the LPS + luteolin group (LPS + Lut). Before the SIc model was induced, luteolin was dissolved in dMSO and injected intraperitoneally for 10 days into LPS + Lut group mice. Nc group and LPS group mice received an equal volume of dMSO for 10 days. On day 11, the animal model of sepsis-induced cardiac dysfunction was induced by intraperitoneal injection of LPS. A total of 12 h after LPS injection, measurements and comparisons were made among the groups. Luteolin administration improved cardiac function, attenuated the inflammatory response, alleviated mitochondrial injury, decreased oxidative stress, inhibited cardiac apoptosis and enhanced autophagy. In addition, luteolin significantly decreased the phosphorylation of AMP-activated protein kinase (AMPK) in septic heart tissue. The protective effect of luteolin was abolished by 3-methyladenine (an autophagy inhibitor) and dorsomorphin (compound c, an AMPK inhibitor), as evidenced by decreased autophagic activity, destabilized mitochondrial membrane potential and increased apoptosis in LPS-treated cardiomyocytes, but was mimicked by 5-aminoimidazole-4-carboxamide ribonucleotide (an AMPK activator), suggesting that luteolin attenuates LPS-induced myocardial injury by increasing autophagy through AMPK activation. Luteolin may be a promising therapeutic agent for treating SIc.

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Section: Discussionmentioning

confidence: 99%

Luteolin attenuates sepsis‑induced myocardial�injury by enhancing autophagy in mice

Song

Fan

et al. 2020

Int J Mol Med

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“…Evidence from a great many animal and cell models points out a key role of Nrf2 in attenuation of diabetes and diabetic complications [41–43]. Previous studies revealed that activating the Nrf2 signaling pathway mediates the cardioprotection of luteolin against oxidative damage [22, 44]. This Nrf2-involved protective effect of luteolin was also demonstrated in diabetic nervous systems and hypercholesterolemic I/R hearts [28, 45].…”

Section: Discussionmentioning

confidence: 99%

Luteolin Attenuates Cardiac Ischemia/Reperfusion Injury in Diabetic Rats by Modulating Nrf2 Antioxidative Function

Xiao

Mao

Wang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Luteolin has been reported to attenuate ischemia/reperfusion (I/R) injury in the diabetic heart through endothelial nitric oxide synthase- (eNOS-) related antioxidative response. Though the nuclear factor erythroid 2-related factor 2 (Nrf2) is regarded as a key endogenous factor to reduce diabetic oxidative stress, whether luteolin reduces cardiac I/R injury in the diabetic heart via enhancing Nrf2 function needs to be clarified. We hypothesized that pretreatment with luteolin could alleviate cardiac I/R injury in the diabetic heart by affecting the eNOS/Nrf2 signaling pathway. The diabetic rat was produced by a single injection of streptozotocin (65 mg/kg, i.p.) for 6 weeks, and then, luteolin (100 mg/kg/day, i.g.), eNOS inhibitor L-NAME, or Nrf2 inhibitor brusatol was administered for the succedent 2 weeks. After that, the isolated rat heart was exposed to 30 min of global ischemia and 120 min of reperfusion to establish I/R injury. Luteolin markedly ameliorated cardiac function and myocardial viability; upregulated expressions of heme oxygenase-1, superoxide dismutase, glutathione peroxidase, and catalase; and reduced myocardial lactate dehydrogenase release, malondialdehyde, and 8-hydroxydeoxyguanosine in the diabetic I/R heart. All these ameliorating effects of luteolin were significantly reversed by L-NAME or brusatol. Luteolin also markedly reduced S-nitrosylation of Kelch-like ECH-associated protein 1 (Keap1) and upregulated Nrf2 and its transcriptional activity. This effect of luteolin on Keap1/Nrf2 signaling was attenuated by L-NAME. These data reveal that luteolin protects the diabetic heart against I/R injury by enhancing eNOS-mediated S-nitrosylation of Keap1, with subsequent upregulation of Nrf2 and the Nrf2-related antioxidative signaling pathway.

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“…The inhibition of Rac1 could ameliorate neuronal oxidative stress damage through the PI3K/Akt/mTOR pathway [29]. Ruiqi et al reported that the Luteolin ameliorates inorganic mercury-induced cardiac injury through the PI3K/Akt/Nrf2 signaling pathway to reduce oxidative stress levels [30]. Therefore, we speculated that glutamine could exert the effect of antioxidant stress through the PI3K/Akt signaling pathway, protecting cell survival.…”

Section: Discussionmentioning

confidence: 99%

Glutamine protects against oxidative stress injury through inhibiting the activation of PI3K/Akt signaling pathway in parkinsonian cell model

Zhao

Wang

et al. 2019

Environ Health Prev Med

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BackgroundParkinson’s disease is a neurodegenerative disorder, and recent studies suggested that oxidative stress contributes to the degeneration of dopamine cell in Parkinson’s disease. Glutamine also has a positive role in reducing oxidative stress damage. In this study, we hypothesized that glutamine offers protection against oxidative stress injury in 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson’s disease cell model.MethodsMPP+ was used to induce PD models in PC12 cells and classified into control, M0 (MPP+), G0 (glutamine), and M0+G0 groups. CCK-8 and AO/EB staining assays were used to examine cell proliferation and apoptosis, respectively. Western blotting was applied to examine the protein expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR.ResultsWe showed that glutamine suppressed cytotoxicity induced by MPP+ in PC12 cells. MPP+ decreased the superoxide dismutase and glutathione peroxidase activity and increased the malondialdehyde content, which were restored by glutamine. Moreover, MPP+ increased the expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR, which were inhibited by glutamine. And the antioxidant capacity of glutamine on PC12 cells could be improved by LY294002 and inhibited by IGF-1.ConclusionThese results suggest that glutamine strengthens the antioxidant capacity in PC12 cells induced by MPP+ through inhibiting the activation of the PI3K/Akt signaling pathway. The effects of glutamine should be investigated and the protective mechanism of glutamine in PD must be explored in future studies.

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Luteolin-mediated PI3K/AKT/Nrf2 signaling pathway ameliorates inorganic mercury-induced cardiac injury

Cited by 72 publications

References 43 publications

Luteolin attenuates sepsis‑induced myocardial�injury by enhancing autophagy in mice

Luteolin attenuates sepsis‑induced myocardial�injury by enhancing autophagy in mice

Luteolin Attenuates Cardiac Ischemia/Reperfusion Injury in Diabetic Rats by Modulating Nrf2 Antioxidative Function

Glutamine protects against oxidative stress injury through inhibiting the activation of PI3K/Akt signaling pathway in parkinsonian cell model

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