Anti-Inflammatory Effect of L-carvone on Lipopolysaccharide-Induced Acute Lung Injury

Abstract

Acute lung injury is among the most serious conditions that affect the lung which is characterized by an exacerbation of inflammatory response that can result from a severe lung infection. The enantiomers of carvone (L and D) are found in various plants species each with special pharmacological effects; where, the levo (L)carvone is chiral monoterpenoid ketone present in the essential oils of dill, caraway, and spearmint and possess many pharmacological properties like antioxidant, anti-inflammatory, antimicrobial, antidiabetic, and anticonvulsant effects. In a previous study, L-carvone inhibited mucositis induced by irinotecan. This study is the first to evaluate the lung anti-inflammatory protective effects, and potential mechanism of action of L-carvone in acute lung injury induced by lipopolysaccharide by measuring the gene expression level of inflammatory mediators (tumor necrosis factor-alpha, cyclooxygenase-2 and nuclear factor-kappa of activated B cells) by conducting real-time quantitative polymerase chain reaction test. Fifty adult mice were allocated into 5 Groups as follows: - control group (mice received normal saline, Group I). Mice in the -induction group received (lipopolysaccharide 10mg/kg/day intraperitoneally, Group II) and were euthanized 2 hours later. Group III (Vehicle group, Mice received corn oil 0.1 ml + lipopolysaccharide 10 mg/kg). Mice in the -treatment groups received either [(50mg/kg/day), Group IV] or [(100mg/kg/day), Group V] of oral L-carvone for 5 consecutive days before lipopolysaccharide injection. Pretreatment with L-carvone (50mg/kg/day) (Group IV) markedly attenuated pro-inflammatory cytokines as observed by significant (P<0.05) reduction in mRNA expressions of tumor necrosis factor-alpha (7.56 ±1.195 vs 29.20±4.9) and cyclooxygenase 2 (5.72±0.329 vs.10.58 ±0.777) in mice’s lung tissue compared to those in the induction group, non-treated mice (lipopolysaccharide model group) (Group II). Increasing the dose of L-carvone to 100mg/kg/day (Group V) also resulted in a significant reduction in mRNA expressions of tumor necrosis factor-alpha (7.84±1.4 vs 29.20±4.9) and cyclooxygenase2 (4.589± 0.946 vs 10.58±1.641) compared to that expression in the induction group, non-treated mice (lipopolysaccharide model group) (Group II); however, the attenuating effect is dose-independent. Furthermore, the results revealed that nuclear factor-kappa of activated B cells mRNA gene expression was significantly lowered by L-carvone 50mg/kg /day (Group IV) (5.01±0.826 vs 11.88±1.227) and 100mg/kg /day (Group V) (6.81±1.362 vs 11.88±1.227) compared to induction group, non-treated mice (lipopolysaccharide model, Group II). Conclusion This study clearly revealed that L-carvone exerted anti-inflammatory and lung-protective effects on lipopolysaccharide-induced acute lung injury. The observed effects were dose-independent and resulted from hampering of the NF-κB signaling pathway.