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Anti-inflammatory activity of arctigenin against PCV2 infection in a mouse model.

ABSTRACT: Arctigenin (ACT) is a novel anti-inflammatory lignan extracted from Arctium lappa L, a herb commonly used in traditional Chinese herbal medicine. In this study, we investigated the molecular mechanism whereby ACT inhibits PCV2 infection-induced proinflammatory cytokine production in vitro and in vivo. We observed that in PCV2 infection+ACT treated PK-15 cells, proinflammatory cytokine production was significantly reduced, compared to the PCV2-infected cells. The transfection and luciferase reporter assay confirmed that ACT suppressed NF-κB signalling pathway activation following PCV2 infection in PK-15 cells. Furthermore, western blotting demonstrated that ACT suppressed the NF-κB signal pathway in PCV2 infection-stimulated PK-15 cells by inhibiting the translocation of p65 from the cytoplasm to the nucleus and IκBα phosphorylation. BALB/c mice were used as a model to evaluate the anti-inflammatory effect of ACT in vivo. We found that the BALB/c mice inoculated with PCV2 infection + ACT treated showed a significant reduction of proinflammatory cytokine production in serum, lung and spleen tissue, compared to the PCV2-infected mice. Western blotting confirmed that ACT suppressed the NF-κB signal pathway in PCV2-infected mice by inhibiting the translocation of p65 from the cytoplasm to the nucleus and IκBα phosphorylation in lung tissue. Our studies first demonstrate that ACT inhibits PCV2 infection-induced proinflammatory cytokine production by suppressing the phosphorylation and nuclear translocation of NF-κB in vitro and in vivo. These results will help further develop ACT as a Traditional Chinese herbal medicine remedy in the treatment of porcine circovirus-associated diseases.

SUBMITTER: Wu L

PROVIDER: S-EPMC8959337 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Anti-inflammatory activity of arctigenin against PCV2 infection in a mouse model.

Wu Lijun L Chen Jie J Zhou Danna D Chen Runshan R Chen Xiabing X Shao Zhiyong Z Yang Wenhai W He Bin B

Veterinary medicine and science 20211216 2

Arctigenin (ACT) is a novel anti-inflammatory lignan extracted from Arctium lappa L, a herb commonly used in traditional Chinese herbal medicine. In this study, we investigated the molecular mechanism whereby ACT inhibits PCV2 infection-induced proinflammatory cytokine production in vitro and in vivo. We observed that in PCV2 infection+ACT treated PK-15 cells, proinflammatory cytokine production was significantly reduced, compared to the PCV2-infected cells. The transfection and luciferase repor ...[more]

PMID: 34914190

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Project description:4R is a tobacco cembranoid that binds to and modulates cholinergic receptors and exhibits neuroprotective and anti-inflammatory activity. Given the established function of the cholinergic system in pain and inflammation, we propose that 4R is also analgesic. Here, we tested the hypothesis that systemic 4R treatment decreases pain-related behaviors and peripheral inflammation via modulation of the alpha 7 nicotinic acetylcholine receptors (α7 nAChRs) in a mouse model of inflammatory pain. We elicited inflammation by injecting Complete Freund's Adjuvant (CFA) into the hind paw of male and female mice. We then assessed inflammation-induced hypersensitivity to cold, heat, and tactile stimulation using the Acetone, Hargreaves, and von Frey tests, respectively, before and at different time points (2.5 h - 8d) after a single systemic 4R (or vehicle) administration. We evaluated the contribution of α7 nAChRs 4R-mediated analgesia by pre-treating mice with a selective antagonist of α7 nAChRs followed by 4R (or vehicle) administration prior to behavioral tests. We assessed CFA-induced paw edema and inflammation by measuring paw thickness and quantifying immune cell infiltration in the injected hind paw using hematoxylin and eosin staining. Lastly, we performed immunohistochemical and flow cytometric analyses of paw skin in α7 nAChR-cre::Ai9 mice to measure the expression of α7 nAChRs on immune subsets. Our experiments show that systemic administration of 4R decreases inflammation-induced peripheral hypersensitivity in male and female mice and inflammation-induced paw edema in male but not female mice. Notably, 4R-mediated analgesia and anti-inflammatory effects lasted up to 8d after a single systemic administration on day 1. Pretreatment with an α7 nAChR-selective antagonist prevented 4R-mediated analgesia and anti-inflammatory effects, demonstrating that 4R effects are via modulation of α7 nAChRs. We further show that a subset of immune cells in the hind paw expresses α7 nAChRs. However, the number of α7 nAChR-expressing immune cells is unaltered by CFA or 4R treatment, suggesting that 4R effects are independent of α7 nAChR-expressing immune cells. Together, our findings identify a novel function of the 4R tobacco cembranoid as an analgesic agent in both male and female mice that reduces peripheral inflammation in a sex-dependent manner, further supporting the pharmacological targeting of the cholinergic system for pain treatment.

Dataset Information

Anti-inflammatory activity of arctigenin against PCV2 infection in a mouse model.

Publications

Anti-inflammatory activity of arctigenin against PCV2 infection in a mouse model.

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