Anti-inflammatory Property of Imperatorin on Alveolar Macrophages and Inflammatory Lung Injury

Abstract

Imperatorin is one of the furanocoumarin derivatives and exists in many medicinal herbs with anticancer, antiviral, antibacterial, and antihypertensive activities. In this study, we examined the anti-inflammatory effects of imperatorin on inflammation-associated lung diseases. Imperatorin reduced iNOS and COX-2 expression and also IL-6 and TNFα production enhanced by zymosan. Imperatorin also inhibited the signaling pathways of JAK/STAT and NF-κB. Moreover, in vivo study also revealed that zymosan-induced immune cell infiltration, pulmonary fibrosis, and edema were relieved by imperatorin in mice. We found that imperatorin exerts anti-inflammatory effects that are associated with amelioration of lung inflammation, edema, and rapid fibrosis. Studies on alveolar macrophages also reveal that imperatorin reduced the production of pro-inflammatory mediators and cytokines and inhibited pro-inflammatory JAK1/STAT3 and NF-κB signaling pathways. These results indicate that imperatorin may be a potential anti-inflammatory agent for inflammatory-associated lung diseases.

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

“… Compounds Structure In vitro/in vivo Model (effective dose) Cells (effective concentration) Related pharmacological indicators Related molecular mechanisms Refs. Osthole 134 LPS/H1N1/II/R/T/H (20 mg/kg) NR 8383 (50 μg/mL) MPMs (100 μM) MPO↓ TNF-α↓ IL-6↓ MDA↓ WST-1↑ H 2 O 2 ↓ Down-regulation of f ACE2 Inhibition of NF-κB, AKT and ERK signaling pathways Up-regulation of Nrf-2/Trx-1 signaling pathway [ [375] , [376] , [377] , [378] , [379] , [380] ] Imperatorin 135 Zymosan (4 mg/kg) MH-S (15 μg/mL) MPO↓ TNF-α↓ IL-1β↓ IL-6↓ COX-2↓ iNOS↓ NO↓ PGE-2↓ Inhibition of JAK1/STAT3, MAPK and NF-κB signaling pathways [ 381 , 382 ] Columbianadin 136 LPS (20 mg/kg) A549/MH-S (50 μM) IL-6↓ iNOS↓ NO↓ None [ 383 ] Isofraxidin 137 LPS/H1N1 virus (10 mg/kg) MDCK (0.4 μM) MPO↓ TNF-α↓ IL-1β↓ IL-6↓ COX-2↓ PGE2↓ IL-10↑ MIP-2↓ Down-regulation of AKT and MAPK signaling pathways [ 384 , 385 ] Esculetin 138 LPS (20 mg/kg) A549 (10 μM) MPO↓ TNF-α↓ IL-1β↓ IL-6↓ IL-23↓ Inhibition of RhoA/Rho kinase, AKT/ERK/NF-κB and RORγt/IL-17 signaling pathways [ 386 , 387 ] Esculin 139 LPS (20 mg/kg) MPO↓ TNF-α↓ IL-1β↓ IL-6↓ MDA↓ SOD↑ Inhibition of TLR/NF-κB signaling pathway …”

“…Imperatorin 135 , also an important compound of Peucedanum praeruptorum Dunn, significantly attenuated ALI induced by zymosan or LPS in mice via inhibiting histological changes, lung edema, MPO activity and production of pro-inflammatory mediators TNF-α, IL-1β, IL-6, COX-2, iNOS, NO and PGE-2. Imperatorin exerted these effects through inhibiting the JAK1/STAT3, NF-κB and MAPK signaling pathways [ 381 , 382 ].…”

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

“…In LPS-stimulated DCs, IMP increased IL-10 and suppressed the release of proinflammatory cytokines [72]. Li et al have reported that IMP effectively diminished COX-2, IL-6, TNF-α, and iNOS expression via downregulation of NF-κB and JAK/STAT signaling in alveolar macrophages [74]. In addition, IMP relieved zymosaninduced immune cell infiltration in mice, thereby attenuating lung inflammation, edema, and fibrosis [74].…”

“…Li et al have reported that IMP effectively diminished COX-2, IL-6, TNF-α, and iNOS expression via downregulation of NF-κB and JAK/STAT signaling in alveolar macrophages [74]. In addition, IMP relieved zymosaninduced immune cell infiltration in mice, thereby attenuating lung inflammation, edema, and fibrosis [74]. Although these studies have documented the potent anti-inflammatory activity of IMP, none of them have pointed to the involvement of Nrf2 signaling.…”

The Protective Effects of Imperatorin on Acetaminophen Overdose-Induced Acute Liver Injury

“…Imperatorin (IMP) is a naturally bioactive furanocoumarin from the dry roots of Angelica dahurica (Figure 1(a)), which can be used as an edible flavoring agent in dietary products. It has been proven that IMP possesses various pharmacological effects such as anticancer, anti-inflammatory, and antidiabetic activities [16,17]. Our previous study found that IMP can attenuate DSS-induced colitis through activating PXR/NF-κB and inhibition of NF-κB signaling in mice [18].…”