Zerumbone suppresses the activation of inflammatory mediators in LPS-stimulated U937 macrophages through MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways

Haque, Md. Areeful; Jantan, Ibrahim; Harikrishnan, Hemavathy

doi:10.1016/j.intimp.2018.01.001

Cited by 74 publications

(96 citation statements)

References 41 publications

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“…Therefore, we speculate that ZER can differentially and selectively exert cytotoxic effects depending on cellular condition (especially malignant cells). This notion is consistent with a previous study , showing that ZER can attenuate high glucose- Furthermore, proinflammatory cytokines such as IL-1β and TNF-α are closely associated with the progression of ALI because antagonizing these cytokines ameliorates the severity of liver damages induced by CCl 4 exposure (Sato et al, 2014;Zhu et al, 2010 (Haque, Jantan, & Harikrishnan, 2018;Lee et al, 2018). Also, ZER exerts antiinflammatory and protective effects on lipopolysaccharide-induced acute lung injury through regulating antioxidative enzymes and nuclear factor erythroid 2-related factor and heme oxygenase pathway (Leung et al, 2017).…”

Section: Discussionsupporting

confidence: 92%

“…These findings are further supported by several studies showing anti‐inflammatory activities of ZER. Recent studies have shown that ZER suppresses lipopolysaccharide‐induced inflammation through modulating NF‐κB that plays a principal role in immune responses (Haque, Jantan, & Harikrishnan, ; Lee et al, ). Also, ZER exerts anti‐inflammatory and protective effects on lipopolysaccharide‐induced acute lung injury through regulating antioxidative enzymes and nuclear factor erythroid 2‐related factor and heme oxygenase pathway (Leung et al, ).…”

Section: Discussionmentioning

confidence: 99%

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Dietary zerumbone, a sesquiterpene, ameliorates hepatotoxin‐mediated acute and chronic liver injury in mice

Kim

Yang

Jeong

et al. 2019

Phytotherapy Research

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Acute liver injury (ALI) is a life‐threatening clinical syndrome. Long‐lasting liver injury can lead to chronic hepatic inflammation and fibrogenic responses. Zerumbone (ZER), the main constituent of rhizomes of Zingiber zerumbet Smith, has a variety of functions including anticancer activity. We investigated the role of ZER on the progression of hepatotoxin‐induced liver injury. Single or repeated injection of CCl4 was used to induce acute or chronic liver injury, respectively. Mice were orally administered with ZER (10, 50 mg/kg) during the experimental period. Histopathologic analysis and serum biochemical levels revealed that ZER had hepatoprotective activities against ALI. Similar effects of ZER on injured livers were confirmed by analyses of inflammation and apoptosis‐related genes. Western blot analysis showed that protein levels of apoptotic molecules were decreased, whereas antiapoptotic protein levels were conversely increased in injured livers treated with ZER. Furthermore, chronic liver injury and its associated fibrogenesis in mice were reduced by ZER treatment. These findings from our in vivo experiments further indicate that ZER could alleviate hepatocellular toxicity and inhibit activation of primary hepatic stellate cells. Our results suggest that ZER might have potential as a safe and prophylactic alternative to prevent acute and chronic liver injury.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Dietary zerumbone, a sesquiterpene, ameliorates hepatotoxin‐mediated acute and chronic liver injury in mice

Kim

Yang

Jeong

et al. 2019

Phytotherapy Research

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“…The powdered sample (1.75 kg) was extracted with 80% ethanol (3 × 3 L) for 3 days at 25°C. The filtrates were concentrated by using a rotary evaporator at 37–40°C, followed by freeze‐drying to produce a crude Z. zerumbet extract (248.0 g; Haque et al, ). The crude extract was then stored at 4°C until further use.…”

Section: Methodsmentioning

confidence: 99%

“…Among the bioactive metabolites present in Z. zerumbet , zerumbone has been comprehensively studied for numerous pharmacological perspectives (Haque, Jantan, & Bukhari, ). Our previous study indicated that Z. zerumbet and zerumbone suppressed the activation of inflammatory mediators in lipopolysaccharide (LPS)‐induced U937 macrophages through the MyD88‐dependent NF‐κB/MAPK/PI3K‐Akt signaling pathways (Haque, Jantan, & Harikrishnan, , ). However, there is little scientific information on the immunomodulatory effects of Z. zerumbet on the humoral and cellular components of the immune system.…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive effects of the standardized extract of Zingiber zerumbet on innate immune responses in Wistar rats

Ghazalee

Jantan

Arshad

et al. 2019

Phytotherapy Research

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Zingiber zerumbet rhizome has been used in traditional medicine mainly for the treatment of various immune-inflammatory related ailments and has been shown to exhibit a wide spectrum of biological effects especially antioxidant and anti-inflammatory activities. The present study was aimed to investigate the immunosuppressive effects of the standardized 80% ethanol extract of Z. zerumbet at 100, 200, and 400 mg/kg on the innate immune responses in male Wistar rats. The immune parameters determined were chemotaxis of neutrophils, Mac-1 expression, engulfment of Escherichia coli by neutrophils, reactive oxygen species production, and plasma lysozyme and ceruloplasmin levels. Zerumbone was qualitatively and quantitatively determined in the extract by using a validated reversed-phase HPLC, whereas liquid chromatography tandem-mass spectrometry (LC -MS/MS) was used to profile the secondary metabolites. Z. zerumbet significantly inhibited the migration of neutrophils, expressions of CD11b/CD18 integrin, phagocytic activity, and production of reactive oxygen species in a dose-dependent manner. The extract also dose-dependently inhibited the expressions of lysozyme and ceruloplasmin in the rat plasma. Z. zerumbet extract possessed strong inhibitory effects on the innate immune responses and has potential to be developed into an effective immunosuppressive agent.

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“…Several studies have reported that the activation of MAPKs leads to increased production of the pro-inflammatory mediators. Therefore, NF-B and MAPKs signaling pathways have been considered to be potential targets for antiinflammatory drugs (9,(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

PEP-1-GLRX1 Protein Exhibits Anti-Inflammatory Effects by Inhibiting the Activation of MAPK and NF-κB Pathways in Raw 264.7 Cells

et al. 2020

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Glutaredoxin 1 (GLRX1) has been recognized as an important regulator of redox signaling. Although GLRX1 plays an essential role in cell survival as an antioxidant protein, the function of GLRX1 protein in inflammatory response is still under investigation. Therefore, we wanted to know whether transduced PEP-1-GLRX1 protein inhibits lipopolysaccharide (LPS)-and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced inflammation. In LPS-exposed Raw 264.7 cells, PEP-1-GLRX1 inhibited cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), activation of mitogen activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-B) expression levels. In a TPA-induced mouse-ear edema model, topically applied PEP-1-GLRX1 transduced into ear tissues and significantly ameliorated ear edema. Our data reveal that PEP-1-GLRX1 attenuates inflammation in vitro and in vivo, suggesting that PEP-1-GLRX1 may be a potential therapeutic protein for inflammatory diseases. [BMB Reports 2020; 53(2): 106-111] BMB Rep. 2020; 53(2): 106-111 www.bmbreports.org

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Zerumbone suppresses the activation of inflammatory mediators in LPS-stimulated U937 macrophages through MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways

Cited by 74 publications

References 41 publications

Dietary zerumbone, a sesquiterpene, ameliorates hepatotoxin‐mediated acute and chronic liver injury in mice

Dietary zerumbone, a sesquiterpene, ameliorates hepatotoxin‐mediated acute and chronic liver injury in mice

Immunosuppressive effects of the standardized extract of Zingiber zerumbet on innate immune responses in Wistar rats

PEP-1-GLRX1 Protein Exhibits Anti-Inflammatory Effects by Inhibiting the Activation of MAPK and NF-κB Pathways in Raw 264.7 Cells

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