Protective effect of carnosic acid against paraquat-induced redox impairment and mitochondrial dysfunction in SH-SY5Y cells: Role for PI3K/Akt/Nrf2 pathway

Oliveira, Marcos Roberto de; Ferreira, Gustavo C.; Schuck, Patrícia Fernanda

doi:10.1016/j.tiv.2015.12.005

Cited by 76 publications

(32 citation statements)

References 64 publications

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“…Naringenin has also been shown to inhibit the UVB-induced reduction of Nrf2 mRNA expression in mouse skin [35]. Hydroxytyrosol from olive extract and carnosic acid have also been shown to increase Nrf2 expression in other cell lines [54,55]. Furthermore, formulations F1 and F2 showed a significant reduction in the percent of late apoptosis detected after 24 h in UVB-irradiated keratinocytes.…”

Section: Discussionmentioning

confidence: 98%

Rosemary Diterpenes and Flavanone Aglycones Provide Improved Genoprotection against UV-Induced DNA Damage in a Human Skin Cell Model

et al. 2020

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Overexposure to solar ultraviolet (UV) radiation is the major cause of a variety of cutaneous disorders, including sunburn, photoaging, and skin cancers. UVB radiation (290–320 nm) causes multiple forms of DNA damage, p53 induction, protein and lipid oxidation, and the generation of harmful reactive oxygen species (ROS). In recent years, botanicals containing polyphenols with antioxidant and anti-inflammatory properties as skin photoprotective agents have emerged. This study evaluated the protective effects of two formulations against UVB-induced damage in a skin cell model. One of the formulations (F2) contained a combination of citrus and olive extracts and the other one (F1) also contained a rosemary extract. The antioxidant capacity of both formulations was estimated by different in vitro methods, and the cell viability, intracellular ROS generation, mitochondrial depolarization, and DNA damage were studied in UVB-irradiated human keratinocytes. Both formulations exerted photoprotective effects on skin cells and decreased mitochondrial depolarization and DNA damage. F1 which contained iridoids, rosemary diterpenes, glycosides and aglycones of citrus flavanones, and monohydroxylated flavones exhibited higher cellular photoprotective effects and mitochondrial membrane potential restoration, as well as an enhanced capacity to decrease DNA double strand breaks and the DNA damage response. In contrast, F2, which contained mostly iridoids, citrus flavanone aglycones, and mono- and dihydroxylated flavones, exhibited a higher capacity to decrease intracellular ROS generation and radical scavenging capacity related to metal ion chelation. Both formulations showed a similar capability to decrease the number of apoptotic cells upon UVB radiation. Based on our results and those of others, we postulate that the stronger capacity of F1 to protect against UVB-induced DNA damage in human keratinocytes is related to the presence of rosemary diterpenes and citrus flavanone aglycones. Nevertheless, the presence of the dihydroxylated flavones in F2 may contribute to inhibiting the generation of metal-related free radicals. To confirm the efficacy of these formulations as potential candidates for oral/topical photoprotection, human trials are required to circumvent the limitations of the cellular model.

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Section: Discussionmentioning

confidence: 98%

Rosemary Diterpenes and Flavanone Aglycones Provide Improved Genoprotection against UV-Induced DNA Damage in a Human Skin Cell Model

et al. 2020

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“…Nevertheless, silymarin could reduce the toxic effects of paraquat and consequently increases vitamin C levels due to its antioxidant properties. On the other hand, paraquat can induce lipid oxidation and protein carbonyl (PC) production through ROS (36,37). MDA is considered as a lipid peroxidation biomarker (38).…”

Section: Discussionmentioning

confidence: 99%

Protective and anti-inflammatory effects of silymarin on paraquat-induced nephrotoxicity in rats

Sharifi-Rigi¹,

Heidarian²

2019

J Herbmed Pharmacol

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“…The Nrf2 signaling pathway, a primary host defense, plays an imperative role in maintaining the structural and functional integrity of mitochondria, which is of extraordinary importance under oxidative stress conditions [42]. In fact, recent studies have shown that numerous bioactive molecules, including natural compounds, were dependent on Nrf2 activation to induce various antioxidant enzymes expression, such as HO-1, GCLM, GCLC and NQO1, which are essential for inhibiting redox impairment and mitochondrial dysfunction [43][44][45]. It has been reported that Daph could protect from carcinogenesis via upregulation of Nrf2 and HO-1 protein expression and enhance the ability of potential antioxidants in rats [24].…”

Section: Discussionmentioning

confidence: 99%

Daphnetin-mediated Nrf2 antioxidant signaling pathways ameliorate tert-butyl hydroperoxide (t-BHP)-induced mitochondrial dysfunction and cell death

Liu

Zhou

et al. 2017

Free Radical Biology and Medicine

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Daphnetin (Daph), a natural coumarin derivative isolated from plants of the Genus Daphne, possesses abundant biological activities, such as anti-inflammatory, antioxidant and anticancer properties. In the present study, we focused on investigating the protective effect of Daph against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage, mitochondrial dysfunction and the involvement of underlying molecular mechanisms. Our findings indicated that Daph effectively inhibited t-BHP-stimulated cytotoxicity, cell apoptosis, and mitochondrial dysfunction, which are associated with suppressed reactive oxygen species (ROS) generation, decreased malondialdehyde (MDA) formation, increased superoxide dismutase (SOD) levels and glutathione (GSH)/GSSG (oxidized GSH) ratio. Further investigation indicated that Daph significantly suppressed cytochrome c release and NLRP3 inflammasome activation and modulated apoptosis-related protein Bcl-2, Bax, and caspase-3 expression. Moreover, Daph dramatically induced the expression of the glutamate-cysteine ligase modifier (GCLM) subunit and the glutamate-cysteine ligase catalytic (GCLC) subunit, heme oxygenase-1 (HO-1), and NAD (P) H: quinone oxidoreductase (NQO1), which is largely dependent on upregulating the nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation, reducing the Keap1 protein expression, and strengthening the antioxidant response element (ARE) promoter activity. Additionally, Daph remarkably activated a c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation, but ERK and JNK inhibitor pretreatment exhibited an evident decrease of the level of Daph-enhanced Nrf2 nuclear translocation. Furthermore, Daph exposure suppressed t-BHP-induced cytotoxicity and ROS overproduction, which are mostly blocked in Nrf2 knockout RAW 264.7 cells and peritoneal macrophages. Accordingly, Daph exhibited protective roles against t-BHP-triggered oxidative damage and mitochondrial dysfunction by the upregulation of Nrf2 antioxidant signaling pathways, which may be involved in the activation of JNK and ERK.

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Protective effect of carnosic acid against paraquat-induced redox impairment and mitochondrial dysfunction in SH-SY5Y cells: Role for PI3K/Akt/Nrf2 pathway

Cited by 76 publications

References 64 publications

Rosemary Diterpenes and Flavanone Aglycones Provide Improved Genoprotection against UV-Induced DNA Damage in a Human Skin Cell Model

Rosemary Diterpenes and Flavanone Aglycones Provide Improved Genoprotection against UV-Induced DNA Damage in a Human Skin Cell Model

Protective and anti-inflammatory effects of silymarin on paraquat-induced nephrotoxicity in rats

Daphnetin-mediated Nrf2 antioxidant signaling pathways ameliorate tert-butyl hydroperoxide (t-BHP)-induced mitochondrial dysfunction and cell death

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