Preventive Effects of Velvet Antler <i>(Cervus elaphus)</i> against Lipopolysaccharide‐Induced Acute Lung Injury in Mice by Inhibiting MAPK/NF‐<i>κ</i>B Activation and Inducing AMPK/Nrf2 Pathways

Chang, Jui-Shu; Lin, Hung-Jen; Deng, Jeng-Shyan; Wu, Wen‐Tzu; Huang, Shyh-Shyun; Huang, Guan‐Jhong

doi:10.1155/2018/2870503

Cited by 26 publications

(26 citation statements)

References 38 publications

(40 reference statements)

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“…In the MAPK family, a series of protein kinases, such as JNK, Erk, and p38MAPK, are involved in diverse cellular responses, including inflammation-related pathways. These MAPKs are activated by either extracellular or intracellular signals [43,44], which in turn promotes early pro-inflammatory cytokine production during the inflammatory process [45][46][47]. The MAPK signaling pathway is known to be activated in response to LPS-induced ALI [11,48,49].…”

Section: Discussionmentioning

confidence: 99%

Spiraea prunifolia var. simpliciflora Attenuates Oxidative Stress and Inflammatory Responses in a Murine Model of Lipopolysaccharide-Induced Acute Lung Injury and TNF-α-Stimulated NCI-H292 Cells

Lee

Shin

et al. 2020

Antioxidants

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Spiraea prunifolia var. simpliciflora (SP) is traditionally used as an herbal remedy to treat fever, malaria, and emesis. This study aimed to evaluate the anti-oxidative and anti-inflammatory properties of the methanol extract of SP leaves in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. SP decreased the number of inflammatory cells and the levels of TNF-α, interleukin (IL)-1β, and IL-6 in the bronchoalveolar lavage fluid, and inflammatory cell infiltration in the lung tissues of SP-treated mice. In addition, SP significantly suppressed the mRNA and protein levels of TNF-α, IL-1β, and IL-6 in TNF-α-stimulated NCI-H292 cells. SP significantly suppressed the phosphorylation of the mitogen-activated protein kinases (MAPKs) and p65-nuclear factor-kappa B (NF-κB) in LPS-induced ALI mice and TNF-α-stimulated NCI-H292 cells. SP treatment enhanced the nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2) with upregulated antioxidant enzymes and suppressed reactive oxygen species (ROS)-mediated oxidative stress in the lung tissues of LPS-induced ALI model and TNF-α-stimulated NCI-H292 cells. Collectively, SP effectively inhibited airway inflammation and ROS-mediated oxidative stress, which was closely related to its ability to induce activation of Nrf2 and inhibit the phosphorylation of MAPKs and NF-κB. These findings suggest that SP has therapeutic potential for the treatment of ALI.

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Section: Discussionmentioning

confidence: 99%

Spiraea prunifolia var. simpliciflora Attenuates Oxidative Stress and Inflammatory Responses in a Murine Model of Lipopolysaccharide-Induced Acute Lung Injury and TNF-α-Stimulated NCI-H292 Cells

Lee

Shin

et al. 2020

Antioxidants

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“…MAPK and NF‐κB are vital factors that play an essential role in adjusting inflammatory reactions by affecting the expression of numerous inflammatory cytokine genes . NF‐κB and MAPK can be stimulated by various factors, such as LPS and RIR . NF‐κB and MAPK can modulate the transcription of a great number of target genes.…”

Section: Discussionmentioning

confidence: 99%

Lipoxin A4 ameliorates renal ischaemia–reperfusion‐induced acute lung injury in rats

Liu

Qian

Chang

2018

Clin Exp Pharma Physio

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Lipoxin A4 (LA4), a bioactive product of arachidonic acid, has been shown to exert strong anti-inflammatory activity. By contrast, the anti-inflammatory action of LA4 in a renal ischaemia-reperfusion (RIR)-mediated acute lung inflammation (ALI) model and the potential pathogenesis of the condition is still unclear. The aim of the current research was to investigate the effect of LA4 on RIR-induced ALI. The rat ALI model was induced by RIR. LA4 was injected via the tail vein immediately after RIR. The results indicate that LA4 markedly inhibits inflammatory cells infiltration, attenuates myeloperoxidase activity, and reduces the concentration of inflammatory mediators and Toll-like receptor 4 (TLR4) in RIR-induced ALI. Furthermore, LA4 suppressed nuclear factor kappa B (NF-κB) p65 and mitogen-activated protein kinase (MAPK) activation. The protective effect of LA4 in RIR-stimulated ALI was reversed by BOC-2 (an antagonist of the LA4 receptor). These results indicate that LA4 exerts powerful anti-inflammatory functions in RIR-induced ALI by attenuating TLR4 expression via MAPK and NF-κB signalling. Accordingly, LA4 might be an underlying treatment drug for RIR-induced ALI.

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“…According to reports, sika deer antler protein (SDAPR) can protect cisplatin‐induced and gentamicin‐induced AKI (Sun et al, ; Yang et al, ). The study also showed that antlers can resist LPS‐induced acute lung injury by activating AMPK/Nrf2 pathway (Chang et al, ). HK‐2 cell lines have been used for pharmacological experiments in vitro on kidney injury models (Vrbová, Roušarová, Brůčková, Česla, & Roušar, ).…”

Section: Introductionmentioning

confidence: 95%

Sika deer antler protein against acetaminophen‐induced oxidative stress and apoptosis in HK‐2 cells via activating Nrf2/keap1/HO‐1 pathway

Ruan

Wang

et al. 2019

J Food Biochem

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Nf-E2-related transcription factor 2 (Nrf2) helps cells fight oxidative stress events in vivo and in vitro by promoting the expression of antioxidants and detoxification enzymes. The necessary factors regulating Nrf2 activity and stability during analgesic nephropathy are not fully understood. Our results suggest that acetaminophen produces nephrotoxicity in HK-2 cells by inhibiting keap1 degradation. APAP subsided Nrf2 nuclear accumulation by inhibition of keap1 degradation, thereby reducing the binding of Nrf2 to ARE, leading to the loss of expression of antioxidant proteins such as HO-1, inducing a series of oxidative stress and apoptosis events. Therefore, Nrf2/ keap1/HO-1 signal transduction pathway has a poor prognosis during analgesic nephrotoxicity. Sika deer antler protein (SDAPR) significantly prevented APAP-induced HK-2 cell damage by constitutively stabilized Nrf2 nuclear retention. Excess APAP leads to a decrease in Nrf2 nuclear translocation, leading to severe oxidative stress, increasing the levels of GSH and MDA in HK-2 cells, and reducing the enzyme activities of SOD and CAT in HK-2 cells. Increased biomarker levels of acute kidney injury (AKI) in HK-2 cells, including kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and cystatin C, decrease the mitochondrial membrane potential in HK-2 cells, and cause mitochondrial dysfunction, it also reduced the ratio of mitochondria-associated apoptotic protein Bax/Bcl-2, leading to cell apoptosis. SDAPR dose dependently accorded protection against acetaminophen-induced nephrotoxicity, oxidative damage, and cell apoptosis by its molecular intervention with Nrf2/ keap1/HO-1 pathway via keap1 degradation. Practical applicationsIn this paper, we investigated the protective effect of SDAPR on APAP-induced AKI in HK-2 cells, and briefly explained its possible mechanism of action, providing a basis for future clinical trials and the development of anti-APAP AKI drugs. K E Y W O R D S acetaminophen, apoptosis, HK-2 cell, Nrf2/keap1/HO-1 pathway, oxidative stress, sika deer antler protein How to cite this article: Ruan H, Wang L, Wang J, et al. Sika deer antler protein against acetaminophen-induced oxidative stress and apoptosis in HK-2 cells via activating Nrf2/keap1/ HO-1 pathway. J Food Biochem. 2019;43:e13067.

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Preventive Effects of Velvet Antler (Cervus elaphus) against Lipopolysaccharide‐Induced Acute Lung Injury in Mice by Inhibiting MAPK/NF‐κB Activation and Inducing AMPK/Nrf2 Pathways

Cited by 26 publications

References 38 publications

Spiraea prunifolia var. simpliciflora Attenuates Oxidative Stress and Inflammatory Responses in a Murine Model of Lipopolysaccharide-Induced Acute Lung Injury and TNF-α-Stimulated NCI-H292 Cells

Spiraea prunifolia var. simpliciflora Attenuates Oxidative Stress and Inflammatory Responses in a Murine Model of Lipopolysaccharide-Induced Acute Lung Injury and TNF-α-Stimulated NCI-H292 Cells

Lipoxin A4 ameliorates renal ischaemia–reperfusion‐induced acute lung injury in rats

Sika deer antler protein against acetaminophen‐induced oxidative stress and apoptosis in HK‐2 cells via activating Nrf2/keap1/HO‐1 pathway

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