β-Caryophyllene attenuates lipopolysaccharide-induced acute lung injury via inhibition of the MAPK signalling pathway

Abstract

Objectives Acute lung injury (ALI) is a pulmonary manifestation of an acute systemic inflammatory response, which is associated with high morbidity and mortality. Accordingly, from the perspective of treating ALI, it is important to identify effective agents and elucidate the underlying modulatory mechanisms. β-Caryophyllene (BCP) is a naturally occurring bicyclic sesquiterpene that has anti-cancer and anti-inflammatory activities. However, the effects of BCP on ALI have yet to be ascertained. Methods ALI was induced intratracheally, injected with 5 mg/kg LPS and treated with BCP. The bone marrow-derived macrophages (BMDMs) were obtained and cultured then challenged with 100 ng/ml LPS for 4 h, with or without BCP pre-treatment for 30 min. Key findings BCP significantly ameliorates LPS-induced mouse ALI, which is related to an alleviation of neutrophil infiltration and reduction in cytokine production. In vitro, BCP was found to reduce the expression of interleukin-6, interleukin-1β and tumour necrosis factor-α, and suppresses the MAPK signalling pathway in BMDMs, which is associated with the inhibition of TAK1 phosphorylation and an enhancement of MKP-1 expression. Conclusions Our data indicate that BCP protects against inflammatory responses and is a potential therapeutic agent for the treatment of LPS-induced acute lung injury.

Protective antioxidative and anti-inflammatory actions of β-caryophyllene against sulfasalazine-induced nephrotoxicity in rat

“…16 Others have likewise shown ameliorative effects for BCP in the treatment of acute lung injury induced by lipopolysaccharide in mice following reductions in several inflammatory markers, including TGFβ. 37 BCP also alleviated cerebral injury induced by ischemiareperfusion in rat as well as deterred lipid accumulation in human hepatocyte subsequent to enhancing the AMPK/ AKT signaling network in the targeted cells. 38,39 The present data agree with several earlier reports and advocate that BCP could be used as renoprotective agent against SFZ-induced renal injury by concurrently suppressing NF-κB and TGF-β1, and promoting renal antioxidant capacity via Nrf2-dependent pathways.…”

“…16 Others have likewise shown ameliorative effects for BCP in the treatment of acute lung injury induced by lipopolysaccharide in mice following reductions in several inflammatory markers, including TGF-β. 37 BCP also alleviated cerebral injury induced by ischemia-reperfusion in rat as well as deterred lipid accumulation in human hepatocyte subsequent to enhancing the AMPK/AKT signaling network in the targeted cells. 38,39…”

“…38,39 The present data agree with several earlier reports and advocate that BCP could be used as renoprotective agent against SFZ-induced renal injury by concurrently suppressing NF-κB and TGF-β1, and promoting renal antioxidant capacity via Nrf2-dependent pathways. 15,16,37 Furthermore, preclinical studies have also demonstrated remedial effects of BCP for the treatment of IBD and arthritis in rats. 40,41 Therefore, we suggest that SFZ and BCP co-therapy may provide a superlative treatment strategy for rheumatoid arthritis and IBD by enhanced anti-inflammatory actions as well as by preventing SFZ-induced renal injury.…”

Antioxidative and Anti-Inflammatory Protective Effects of β-Caryophyllene against Amikacin-Induced Nephrotoxicity in Rat by Regulating the Nrf2/AMPK/AKT and NF-κB/TGF-β/KIM-1 Molecular Pathways

“…Similar effects were also shown after using BCP for attenuating sulfasalazine-induced renal damage that involved reductions in NF-κB and TGF-β alongside increased Nrf2, AMPK, and AKT concentrations [15]. BCP therapy also reduced lipopolysaccharide-induced acute lung injury in mice by decreasing a variety of inflammatory cytokines, including TGF-β [52]. Likewise, Ullah et al documented anti-inflammatory actions for BCP by suppressing TLR activity and upregulating the AMPK pathway in the nervous system [53].…”

β-Caryophyllene Ameliorates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis through the Downregulation of Mitogen-Activated Protein Kinase/EGR1/TSLP Signaling Axis

“…β-Caryophyllene (BCP, CAS:87-44-5, trans -4,11,11-trimethyl-8-methylenebicyclo[7,2,0]undec-4-ene; Figure 1 A) is a naturally occurring bicyclic sesquiterpene compound that acts as a natural agonist of the CB2 receptor [ 18 ]. Previous studies have demonstrated that BCP inhibits the production of proinflammatory cytokines in immune cells [ 18 ] and exerts anti-inflammatory effects in vivo [ 19 , 20 ]. Based on these findings, we hypothesized that BCP, with its anti-inflammatory properties, might have beneficial effects when used as a topical therapeutic agent for AD treatment.…”