Sinomenine Protects PC12 Neuronal Cells against H2O2-induced Cytotoxicity and Oxidative Stress via a ROS-dependent Up-regulation of Endogenous Antioxidant System

Fan, Hua; Shu, Qing; Guan, Xin-Lei; Zhao, Jiegang; Yan, Jize; Li, Xiangming; Liu, Jiangbo; Jia, Zhaohui; Shi, Jian; Li, Juan

doi:10.1007/s10571-017-0469-1

Cited by 19 publications

(12 citation statements)

References 28 publications

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“…The present study investigated the effects of SIN on AS, and an AS mouse model was created and treated with different concentrations of SIN (10, 30, and 50 mg/kg). Because pro-inflammatory cytokines and oxidative stress are involved in the development of AS, and because SIN has anti-inflammatory and antioxidant effects [ 18 , 32 , 33 ], the study determined the markers of inflammation (TNF-α, IL-1β, and IL-6) and oxidative stress (SOD, CAT and GSH-PX), showing that AS mice had higher levels of TNF-α, IL-1β, and IL-6, and lower levels of SOD, CAT, and GSH-PX. SIN treatment reduced the levels of TNF-α, IL-1β, and IL-6 in a dose-dependent manner, and the levels of SOD, CAT, and GSH-PX were dose-dependently increased.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Sinomenine Against Ankylosing Spondylitis and the Underlying Molecular Mechanisms

Dong

2018

Med Sci Monit

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BackgroundThis study aimed to investigate the effect and underlying molecular mechanism of sinomenine (SIN) on ankylosing spondylitis (AS).Material/MethodsTo study the potential role of SIN in the pathogenesis of AS, an AS mouse model was established and mice were treated with different concentrations of SIN (10, 30, and 50 mg/kg, administered intraperitoneally). Markers of inflammation and oxidative stress were determined by ELISA assay. Western blot analysis and qRT-PCR were used to quantify the levels of related proteins and gene mRNA expression.ResultsThe results suggest that AS mice has higher levels of TNF-α, IL-1β, and IL-6 (p<0.01 for all), and lower levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) (p<0.01 for all). SIN treatment reduced the level of TNF-α, IL-1β, and IL-6 in a dose-dependent manner, and the levels of SOD, CAT, and GSH-PX were dose-dependently increased (p<0.05 for all). The results also revealed that NF-κBp65 expression decreased, while the level of IκB increased, in a dose-dependent manner, after SIN treatment in AS mice (p<0.05 for all). The level of p-p38 was dose-dependently reduced in AS mice by SIN treatment (p<0.05). Moreover, SIN inhibited Cox-2 expression in AS mice in a dose-dependent manner (p<0.05).ConclusionsSIN has a beneficial role in AS through suppressing inflammatory mediators and by down-regulating oxidative stress via inhibiting the MAPKp38/NF-κB pathway and Cox-2 expression.

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Section: Discussionmentioning

confidence: 99%

Protective Effects of Sinomenine Against Ankylosing Spondylitis and the Underlying Molecular Mechanisms

Dong

2018

Med Sci Monit

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“…Numerous studies have found that SIN has antioxidant activity in different cells [ 27 , 28 ]. The Nrf2 signaling pathway is the major defense against inflammatory responses and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Sinomenine Regulates Inflammatory Response and Oxidative Stress via Nuclear Factor kappa B (NF-κB) and NF-E2-Related Factor 2 (Nrf2) Signaling Pathways in Ankle Fractures in Children

et al. 2018

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BackgrounThis study aimed to investigate the effects of SIN on ankle fracture and the underlying mechanisms in MG-63 cells.Mateeial/MethodsqRT-PCR and ELISA assay were used to detect the mRNA and protein levels of cytokines in peripheral blood of children with or without ankle fracture. The expression and activity of antioxidant and detoxifying enzymes were detected by ELISA assay. Pretreated MG-63 cells with/without SIN were stimulated with 1 μg/ml bradykinin (BK). A CCK-8 kit was used to detect the cell viability. The cytokines produced from MG-63 cells were detected by Western blotting and qRT-PCR. Moreover, Western blotting was used to detect the levels of p-p38 and p-NF-κB (p65), and the activation level of the Nrf2 signaling pathway was examined by qRT-PCR and Western blotting.ResultsIn this study, we found that compared with the healthy children, the mRNA and protein levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were significantly upregulated in children with ankle fracture. In addition, the expression and activity of antioxidant and detoxifying enzymes were imbalanced in children with ankle fracture. SIN treatment did not have a cytotoxic effect on MG-63 cells. SIN dose-dependently suppressed BK-induced upregulation of IL-1β, IL-6, TNF-α, p-p38, and p-NF-κB (p65). Furthermore, SIN dramatically inhibited oxidative stress induced by BK via balancing the expression and activity of antioxidant and detoxifying enzymes and inhibited the activation of Nrf2 signaling.ConclusionsSIN might be a potential agent for the treatment of ankle fracture through reducing inflammatory response and oxidative stress.

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“…H 2 O 2 is also used to examine the resistance of flies against OH − ‐induced oxidative stress (Fan et al, ). Flies were maintained on their corresponding control diet or phlorizin diet at 25°C for 25 days.…”

Section: Methodsmentioning

confidence: 99%

Apple phlorizin attenuates oxidative stress inDrosophila melanogaster

et al. 2018

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Apple phlorizin has a lot of applications owing to its antioxidant and hepatoprotective properties. This study explored the antioxidant effects and life span‐prolonging activity of apple phlorizin in Drosophila melanogaster. Treatment with apple phlorizin was found to significantly extend the life span and ameliorate the age‐related decline of locomotor function. This life span‐extending activity was associated with the increased activity of superoxide dismutase, catalase, mRNA expression of glutamate–cysteine ligase catalytic subunit, cap‐n‐collar (cnc, homologue of mammalian Nrf2 gene), Keap1, and deacetylase sir2, as well as the downregulation of methuselah. Computational analysis suggested phlorizin could work as a Nrf2 activator and exert its biological activities by interfering with the Keap1 and Nrf2 binding. Therefore, it was concluded that the antioxidant and anti‐aging effects of phlorizin might, at least in part, be mediated through the cooperation with the endogenous stress defense system. Practical applications Phlorizin, from apple peel, has been used as a nutrient for over 100 years. To date, despite extensive research on phlorizin, a report on its effect on the antioxidant system in fruit flies is yet lacking. This report demonstrates that phlorizin can exert a protective effect on antioxidant issues and prolong life in fruit flies, which is valuable in the rational utilization of phlorizin in functional foods.

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Sinomenine Protects PC12 Neuronal Cells against H2O2-induced Cytotoxicity and Oxidative Stress via a ROS-dependent Up-regulation of Endogenous Antioxidant System

Cited by 19 publications

References 28 publications

Protective Effects of Sinomenine Against Ankylosing Spondylitis and the Underlying Molecular Mechanisms

Protective Effects of Sinomenine Against Ankylosing Spondylitis and the Underlying Molecular Mechanisms

Sinomenine Regulates Inflammatory Response and Oxidative Stress via Nuclear Factor kappa B (NF-κB) and NF-E2-Related Factor 2 (Nrf2) Signaling Pathways in Ankle Fractures in Children

Apple phlorizin attenuates oxidative stress inDrosophila melanogaster

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