l-Menthol alleviates cigarette smoke extract induced lung injury in rats by inhibiting oxidative stress and inflammation via nuclear factor kappa B, p38 MAPK and Nrf2 signalling pathways

Abstract

L-Menthol is the main ingredient of peppermint which affects various pharmacological effects such as anti-inflammation and anti-oxidative activity. In this study, we aimed to evaluate the potential effects of L-menthol on cigarette smoke extract (CSE) induced lung injury in rats. Morphology assessment results revealed that administration with L-menthol (5, 10 or 20 mg kg⁻¹ d⁻¹) significantly alleviated CSE-induced lung injury. Besides, L-menthol significantly reduced the inflammatory response by suppressing the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) via downregulating nuclear factor kappa B (NF-κB) and p38 MAPK pathways. Meanwhile, L-menthol decreased the levels of oxidative stress markers including malondialdehyde (MDA) and myeloperoxidase (MPO) whereas it increased the amount of glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) through activation of the Nrf2 pathway. Furthermore, the expression of MMP-9 and TIMP-1 in lungs was reduced after treatment with L-menthol, and this indicated that L-menthol might have a potential effect on airway remodeling. Moreover, immunohistochemistry analyses indicated that L-menthol could suppress the infiltration of CD4⁺ and CD8⁺ T cells in lung tissues and this was probably due to the immune regulation activity of L-menthol. Taken together, our findings support that L-menthol might be a potential candidate for the treatment of CSE-induced lung injury in rats.