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
  • 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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