2. Academic Validation
  3. Osthole Attenuates Macrophage Activation in Experimental Asthma by Inhibitingthe NF-ĸB/MIF Signaling Pathway

Osthole Attenuates Macrophage Activation in Experimental Asthma by Inhibitingthe NF-ĸB/MIF Signaling Pathway

  • Front Pharmacol. 2021 Mar 22;12:572463. doi: 10.3389/fphar.2021.572463.
Ruyi Li 1,  Peng Song 2 3,  Guofang Tang 4,  Jianghong Wei 4,  Lizong Rao 4,  Libing Ma 4,  Ming Jiang 4,  Jianwei Huang 4,  Qing Xu 4,  Jingjie Wu 4,  Qian Lv 4,  Dong Yao 5,  Bo Xiao 5,  Haiming Huang 5,  Liping Lei 5,  Juntao Feng 1,  Biwen Mo 4
Affiliations

Affiliations

  • 1 Key Laboratory of National Clinical Research Center for Respiratory Disease, Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, China.
  • 2 Key Laboratory of Prevention and Treatment for Chronic Diseases by Traditional Chinese Medicine, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou, China.
  • 3 Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 4 Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, Guilin, China.
  • 5 Laboratory of Pulmonary Diseases, Guilin Medical University, Guilin, China.
PMID: 33828480 DOI: 10.3389/fphar.2021.572463
Abstract

Inhibition of activated macrophages is an alternative therapeutic strategy for asthma. We investigated whether a coumarin compound, osthole, isolated from Cnidium monnieri (L.) Cuss, alleviated macrophage activation in vivo and in vitro. Osthole could reduce expression of a marker of activated macrophages, cluster of differentiation (CD)206, in an ovalbumin-challenge model of asthma in mice. Osthole could also inhibit infiltration of inflammatory cells, collagen deposition and production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-ɑ, macrophage migration inhibitory factor (MIF)] in asthmatic mice. In vitro, expression of phosphorylated-IĸBɑ, MIF and M2 cytokines (Ym-1, Fizz-1, arginase-1) in IL-4-induced macrophages decreased upon exposure to the NF-ĸB inhibitor MG-132. In our short hairpin (sh)RNA-MIF-knockdown model, reduced expression of M2 cytokines was detected in the IL-4 + shRNA-MIF group. Osthole could attenuate the proliferation and migration of an IL-4-induced rat alveolar macrophages line (NR8383). Osthole could reduce IL-4-induced translocation of nuclear factor-kappa B (NF-ĸB) in NR8383 cells. Collectively, our results suggest that osthole ameliorates macrophage activation in asthma by suppressing the NF-ĸB/MIF signaling pathway, and might be a potential agent for treating asthma.

Keywords

MIF 46; NF-ĸB; asthma; macrophages; osthole.

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