Paeonol from Hippocampus kuda Bleeler suppressed the neuro-inflammatory responses in vitro via NF-κB and MAPK signaling pathways

Abstract Background Patchouli alcohol (PA) is a tricyclic sesquiterpene extracted from Pogostemonis Herba, which is a traditional Chinese medicine used for therapy of inflammatory diseases. Recent studies have shown that PA has various pharmacological activities, including anti-bacterial and anti-viral effects. Methods In this study, the anti-influenza virus (IAV) activities and mechanisms were investigated both in vitro and in vivo. The inhibitory effects of PA against IAV in vitro were evaluated by plaque assay and immunofluorescence assay. The neuraminidase inhibition assay, hemagglutination inhibition (HI) assay, and western blot assay were used to explore the anti-viral mechanisms. The anti-IAV activities in vivo were determined by mice pneumonia model and HE staining. Results The results showed that PA significantly inhibited different IAV strains multiplication in vitro, and may block IAV infection through inactivating virus particles directly and interfering with some early stages after virus adsorption. Cellular PI3K/Akt and ERK/MAPK signaling pathways may be involved in the anti-IAV actions of PA. Intranasal administration of PA markedly improved mice survival and attenuated pneumonia symptoms in IAV infected mice, comparable to the effects of Oseltamivir. Conclusions Therefore, Patchouli alcohol has the potential to be developed into a novel anti-IAV agent in the future.

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A Novel Combination of Vitamin C, Curcumin and Glycyrrhizic Acid Potentially Regulates Immune and Inflammatory Response Associated with Coronavirus Infections: A Perspective from System Biology Analysis

Nutrients ◽

10.3390/nu12041193 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1193 ◽

Cited By ~ 22

Author(s):

Liang Chen ◽

Chun Hu ◽

Molly Hood ◽

Xue Zhang ◽

Lu Zhang ◽

...

Keyword(s):

Immune Response ◽

Vitamin C ◽

Inflammatory Response ◽

Signaling Pathways ◽

System Biology ◽

Glycyrrhizic Acid ◽

Inflammatory Responses ◽

Mapk Signaling ◽

Gene Target

Novel coronaviruses (CoV) have emerged periodically around the world in recent years. The recurrent spreading of CoVs imposes an ongoing threat to global health and the economy. Since no specific therapy for these CoVs is available, any beneficial approach (including nutritional and dietary approach) is worth investigation. Based on recent advances in nutrients and phytonutrients research, a novel combination of vitamin C, curcumin and glycyrrhizic acid (VCG Plus) was developed that has potential against CoV infection. System biology tools were applied to explore the potential of VCG Plus in modulating targets and pathways relevant to immune and inflammation responses. Gene target acquisition, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment were conducted consecutively along with network analysis. The results show that VCG Plus can act on 88 hub targets which are closely connected and associated with immune and inflammatory responses. Specifically, VCG Plus has the potential to regulate innate immune response by acting on NOD-like and Toll-like signaling pathways to promote interferons production, activate and balance T-cells, and regulate the inflammatory response by inhibiting PI3K/AKT, NF-κB and MAPK signaling pathways. All these biological processes and pathways have been well documented in CoV infections studies. Therefore, our findings suggest that VCG Plus may be helpful in regulating immune response to combat CoV infections and inhibit excessive inflammatory responses to prevent the onset of cytokine storm. However, further in vitro and in vivo experiments are warranted to validate the current findings with system biology tools. Our current approach provides a new strategy in predicting formulation rationale when developing new dietary supplements.

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Bacillus amyloliquefaciens SC06 inhibits ETEC-induced pro-inflammatory responses by suppression of MAPK signaling pathways in IPEC-1 cells and diarrhea in weaned piglets

Livestock Science ◽

10.1016/j.livsci.2013.09.017 ◽

2013 ◽

Vol 158 (1-3) ◽

pp. 206-214 ◽

Cited By ~ 8

Author(s):

Jian Ji ◽

Shenglan Hu ◽

Mingzhu Zheng ◽

Wei Du ◽

Qinqin Shang ◽

...

Keyword(s):

Signaling Pathways ◽

Bacillus Amyloliquefaciens ◽

Inflammatory Responses ◽

Mapk Signaling ◽

Weaned Piglets ◽

Mapk Signaling Pathways

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TLR2 ligand engagement upregulates airway smooth muscle TNFα-induced cytokine production

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00317.2011 ◽

2012 ◽

Vol 302 (9) ◽

pp. L838-L845 ◽

Cited By ~ 24

Author(s):

Melanie Manetsch ◽

Petra Seidel ◽

Udo Heintz ◽

Wenchi Che ◽

J. Margaret Hughes ◽

...

Keyword(s):

Smooth Muscle ◽

Signaling Pathways ◽

Airway Smooth Muscle ◽

Inflammatory Responses ◽

Respiratory Infections ◽

Mapk Signaling ◽

Chronic Obstructive ◽

Tlr2 Expression ◽

Chronic Airway

Airway inflammation and respiratory infections are important factors contributing to disease exacerbation in chronic airway diseases such as asthma and chronic obstructive pulmonary disease. Airway smooth muscle (ASM) cells express Toll-like receptors (TLRs) and may be involved in the amplification of airway inflammatory responses during infectious exacerbations. We determined whether infectious stimuli (mimicked using Pam3CSK4, a synthetic bacterial lipopeptide that binds to TLR2/TLR1) further enhance ASM cell inflammatory responses to TNFα in vitro and the signaling pathways involved. Human ASM cells were pretreated for 1 h with Pam3CSK4 (1 μg/ml) in the absence or presence of TNFα (10 ng/ml), and IL-6 and IL-8 release was measured after 24 h. As expected, stimulation with Pam3CSK4 or TNFα alone induced significant IL-6 and IL-8 release. Furthermore, Pam3CSK4 significantly increased TNFα-induced IL-6 and IL-8 mRNA expression and protein release and neutrophil chemotactic activity. The potentiating effect of Pam3CSK4 on TNFα-induced inflammatory responses was not due to enhanced TLR2 expression nor did it involve augmentation of NF-κB or MAPK signaling pathways. Rather, Pam3CSK4 induced cAMP response element (CRE) binding protein phosphorylation and induced CRE-mediated transcriptional regulation, suggesting that Pam3CSK4 and TNFα are acting in concert to enhance ASM cytokine secretion via parallel transcriptional pathways. Our findings suggest that ASM cells may be involved in the amplification of airway inflammatory responses during infectious exacerbations in chronic airway disease.

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Andrographolide Derivative AL-1 Ameliorates Dextran Sodium Sulfate-Induced Murine Colitis by Inhibiting NF-κB and MAPK Signaling Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6138723 ◽

2019 ◽

Vol 2019 ◽

pp. 1-18 ◽

Cited By ~ 4

Author(s):

Mei Jing ◽

Yuqiang Wang ◽

Lipeng Xu

Keyword(s):

Signaling Pathways ◽

Inflammatory Cytokines ◽

Sodium Sulfate ◽

Mapk Signaling ◽

Dextran Sodium Sulfate ◽

Myeloperoxidase Activity ◽

Altered Expression ◽

Murine Colitis ◽

Mapk Signaling Pathways

Trinitrobenzenesulfonic acid (TNBS) and dextran sodium sulfate (DSS) are commonly used to induce experimental murine ulcerative colitis (UC). Our recent study has demonstrated that a novel andrographolide derivative, AL-1, ameliorated TNBS-induced colitis in mice. However, the effect of AL-1 on DSS-induced murine colitis and the underlying mechanisms are yet unknown. In the present study, we aimed to investigate the therapeutic potential of AL-1 against DSS-induced UC in mice and to define its mechanisms of action. Oral administration of AL-1 attenuated body weight loss, reduced colon length shortening, lowered the disease activity index score, and alleviated colon histological damage. AL-1 significantly inhibited myeloperoxidase activity and suppressed immune inflammatory responses in colonic tissues. Moreover, AL-1 reversed DSS-altered expression of inflammatory cytokines in DSS-induced colitis mice. Importantly, the efficacy of 45 mg/kg of AL-1 was higher than that of 100 mg/kg of the positive control drugs 5-aminosalicylic acid and mesalazine. AL-1 decreased lipopolysaccharide-induced generation of reactive oxygen species and nitric oxide in cultured macrophages in vitro; it also reversed the altered expression of inflammatory cytokines. In both in vivo and in vitro studies, Western blot analysis revealed that AL-1 reduced the expression of phosphorylated NF-κB p65 and IκBα, downregulated the expression of iNOS and COX-2, and attenuated the expression of phosphorylated p38 mitogen-activated protein kinase (MAPK), ERK, and JNK. In conclusion, AL-1 alleviated DSS-induced murine colitis by inhibiting activation of the NF-κB and MAPK signaling pathways. Our data suggest that AL-1 could be a potential new treatment for UC.

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