Kaempferol ameliorates H9N2 swine influenza virus-induced acute lung injury by inactivation of TLR4/MyD88-mediated NF-κB and MAPK signaling pathways

Zhang, Ruihua; Xia, Ai; Duan, Yongjie; Xue, Mingzhu; He, Wen-Xiao; Wang, Cun-Lian; Xu, Tong; Xu, Mingsheng; Liu, Baojian; Li, Chunhong; Wang, Zhijun; Zhang, Ruihong; Wang, Guohua; Shu-fei, Tian; Liu, Huifeng

doi:10.1016/j.biopha.2017.02.081

Cited by 117 publications

(79 citation statements)

References 57 publications

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“…Furthermore, it decreased H9N2 viral titer, and it inhibited the upregulation of toll‐like receptor 4 (TLR4), phosphorylation level of IκBα, myeloid differentiation factor 88 (MyD88), NF‐κB p65 DNA binding activity, NF‐κB p65, and phosphorylation level of MAPKs. These results suggest that kaempferol displays a protective effect on H9N2 virus‐induced inflammation by suppressing TLR4/MyD88‐mediated NF‐κB and MAPKs pathways (Zhang et al, ). In addition, kaempferol has been found to (a) attenuate IL‐32‐induced monocyte differentiation to product macrophage‐like cells, (b) decrease production and mRNA expression of pro‐inflammatory cytokines such as thymic stromal lymphopoietin (TSLP), IL‐1β, TNF‐α, and IL‐8, (c) inhibit the IL‐32‐induced activation of p38 and nuclear factor‐κB in THP‐1 cells, and (d) ameliorate the lipopolysaccharide‐induced production of the inflammatory mediators TSLP, IL‐1β, TNF‐α, IL‐8, and nitric oxide of macrophage‐like cells differentiated by IL‐32 (Nam, Jeong, & Kim, ).…”

Section: Health Perspectivesmentioning

confidence: 94%

“…Recent in vivo and in vitro studies by Zhang et al () revealed that kaempferol attenuates pulmonary edema, myeloperoxidase activity, pulmonary capillary permeability, and numbers of inflammatory cells. It additionally reduced the production of ROS and malondialdehyde, enhanced superoxide dismutase activity, and lowered the overproduction of IL‐1β, TNF‐α, and IL‐6.…”

Section: Health Perspectivesmentioning

confidence: 99%

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Chemo‐preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review

Imran

Rauf

Shah

et al. 2018

Phytotherapy Research

248

141

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Kaempferol, a natural flavonoid present in several plants, possesses a wide range of therapeutic properties such as antioxidant, anticancer, and anti-inflammatory. It has a significant role in reducing cancer and can act as a therapeutic agent in the treatment of diseases and ailments such as diabetes, obesity, cardiovascular diseases, oxidative stress, asthma, and microbial contamination disorders. Kaempferol acts through different mechanisms: It induces apoptosis (HeLa cervical cancer cells), decreases cell viability (G2/M phase), downregulates phosphoinositide 3-kinase (PI3K)/AKT (protein kinase B) and human T-cell leukemia/lymphoma virus-I (HTLV-I) signaling pathways, suppresses protein expression of epithelial-mesenchymal transition (EMT)-related markers including N-cadherin, E-cadherin, Slug, and Snail, and metastasis-related markers such as matrix metallopeptidase 2 (MMP-2). Accordingly, the aim of the present review is to collect information pertaining to the effective role of kaempferol against various degenerative disorders, summarize the antioxidant, anti-inflammatory, anticancer, antidiabetic, and antiaging effects of kaempferol and to review the progress of recent research and available data on kaempferol as a protective and chemotherapeutic agent against several ailments.

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Section: Health Perspectivesmentioning

confidence: 94%

Section: Health Perspectivesmentioning

confidence: 99%

Chemo‐preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review

Imran

Rauf

Shah

et al. 2018

Phytotherapy Research

248

141

View full text Add to dashboard Cite

show abstract

“…Previously, Jiang et al () showed that flavonoids from sea buckthorn inhibited the lipopolysaccharide (LPS)‐induced inflammatory response in RAW264.7 macrophages through MAPK and NF‐κB pathways. Furthermore, some other studies also have demonstrated that quercetin and kaempferol exhibit beneficial effects on pulmonary inflammation in vitro or in vivo (Mitani et al, ; Zhang et al, ); however, there is little scientific evidence showing the effect of TFSB on pulmonary inflammatory diseases, especially chronic bronchitis. Furthermore, the precise mechanisms of these active compounds from sea buckthorn fruit including quercetin and isorhamnetin on the treatment of lung inflammatory responses are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Total flavonoids from sea buckthorn ameliorates lipopolysaccharide/cigarette smoke‐induced airway inflammation

Ren

et al. 2019

Phytotherapy Research

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The total flavonoids from sea buckthorn (TFSB) exhibit a potent anti-inflammatory activity; however, the effect of TFSB on respiratory inflammatory disease is not fully known. The present study evaluated the potential of TFSB to prevent airway inflammation and the underlying mechanism. The results showed that TFSB remarkably inhibited lipopolysaccharide/cigarette smoke extract (LPS/CSE)-induced expression of IL-1β, IL-6, CXCL1, and MUC5AC at both mRNA and protein levels in HBE16 bronchial epithelial cells. TFSB also decreased the production of PGE 2 through inhibition the expression of COX2 in LPS/CSE-stimulated HBE16 cells. Furthermore, bronchoalveolar fluid and histological analyses revealed that LPS/cigarette smoke exposure-induced elevated cell numbers of neutrophils and macrophages in bronchoalveolar fluid, inflammatory cell infiltration, and airway remodeling were remarkably attenuated by TFSB in mice. Immunohistochemical results also confirmed that TFSB decreased the expression of IL-1β, IL-6, COX2, CXCL1, and MUC5AC in LPS/CSexposed mice. Mechanistically, TFSB blocked LPS/CSE-induced activation of ERK, Akt, and PKCα. Molecular docking further confirmed that the main components in TFSB including quercetin and isorhamnetin showed potent binding affinities to MAPK1 and PIK3CG, two upstream kinases of ERK and Akt, respectively. In summary, TFSB exerts a potent protective effect against LPS/CS-induced airway inflammation through inhibition of ERK, PI3K/Akt, and PKCα pathways, suggesting that TFSB may be a novel therapeutic agent for respiratory diseases. KEYWORDS chronic bronchitis, ERK, PI3K/Akt, and PKC pathways, lipopolysaccharide/cigarette smoke, sea buckthorn, total flavonoids

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“…35 MH-S cells, an AM cell line derived from BALB/c mice, retain many of the properties of AMs 36 and has been used as an in vitro model for influenza studies. 37 In our data, two nanoparticulate V-ATPase inhibitors exhibited potent anti-influenza activity in AMs in vitro, and the effectiveness in other respiratory epithelial cells such as A549, Calu-3, RPMI 2650 cells, or a recently developed well-differentiated airway epithelium culture system 38 are of interest for future investigation. Beyond respiratory tract tissues, several ocular epithelial cells have been shown to support productive replication of both avian and human influenza viruses in vitro or ex vivo, 29,[39][40][41][42] and influenza virus has been isolated from the eye of infected birds.…”

Section: Discussionmentioning

confidence: 74%

Antiviral efficacy of nanoparticulate vacuolar ATPase inhibitors against influenza virus infection

Hu¹,

Chen²,

Fang³

et al. 2018

IJN

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BackgroundInfluenza virus infections are a major public health concern worldwide. Conventional treatments against the disease are designed to target viral proteins. However, the emergence of viral variants carrying drug-resistant mutations can outpace the development of pathogen-targeting antivirals. Diphyllin and bafilomycin are potent vacuolar ATPase (V-ATPase) inhibitors previously shown to have broad-spectrum antiviral activity. However, their poor water solubility and potential off-target effect limit their clinical application.MethodsIn this study, we report that nanoparticle encapsulation of diphyllin and bafilomycin improves the drugs’ anti-influenza applicability.ResultsUsing PEG-PLGA diblock copolymers, sub-200 nm diphyllin and bafilomycin nanoparticles were prepared, with encapsulation efficiency of 42% and 100%, respectively. The drug-loaded nanoparticles have sustained drug release kinetics beyond 72 hours and facilitate intracellular drug delivery to two different influenza virus-permissive cell lines. As compared to free drugs, the nanoparticulate V-ATPase inhibitors exhibited lower cytotoxicity and greater in vitro antiviral activity, improving the therapeutic index of diphyllin and bafilomycin by approximately 3 and 5-fold, respectively. In a mouse model of sublethal influenza challenge, treatment with diphyllin nanoparticles resulted in reduced body weight loss and viral titer in the lungs. In addition, following a lethal influenza viral challenge, diphyllin nanoparticle treatment conferred a survival advantage of 33%.ConclusionsThese results demonstrate the potential of the nanoparticulate V-ATPase inhibitors for host-targeted treatment against influenza.

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Kaempferol ameliorates H9N2 swine influenza virus-induced acute lung injury by inactivation of TLR4/MyD88-mediated NF-κB and MAPK signaling pathways

Cited by 117 publications

References 57 publications

Chemo‐preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review

Chemo‐preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review

Total flavonoids from sea buckthorn ameliorates lipopolysaccharide/cigarette smoke‐induced airway inflammation

Antiviral efficacy of nanoparticulate vacuolar ATPase inhibitors against influenza virus infection

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