Modulation of alveolar macrophage innate response in proinflammatory-, pro-oxidant-, and infection- models by mint extract and chemical constituents: Role of MAPKs

Abstract

There is a continuing need for discovering novel primary or adjunct therapeutic agents to treat inflammatory conditions and infections. Natural products have inspired the discovery of several modern therapeutics; however, there is a paucity of mechanistic information on their mode of action. This study investigated the therapeutic potential and mode of action of corn mint’s (Mentha arvensis) leaf extract (ME) in alveolar macrophages (AMs) challenged with model pro-inflammatory (LPS), pro- oxidant (LPS or H2O2), and infection (Mycobacterium) agents and contribution of its dominant constituents rosmarinic acid, l-menthol, and l-menthone. LPS-induced inflammatory response in the murine AM cell line MH-S was significantly reduced in terms of pro-inflammatory cytokines (TNF-α, IL-1α) and nitric oxide (NO) when pre- or post-treated with ME. The ME pretreatment of macrophages led to a significant increase (P≤0.05) in phagocytic activity toward Mycobacterium smegmatis and a greater pathogen clearance in 24h in both ME pre-treated (P≤0.05) and post-treated cells. Significant attenuation (P≤0.01) of reactive oxygen species (ROS) production in LPS- or H2O2-treated macrophages by pretreatment with whole mint extract (ME) was accounted for in part by the mint constituents rosmarinic acid and l-menthone. Attenuation of pro-inflammatory response by ME pretreatment coincided with the significant reduction in total and phosphorylated JNK1/2, decrease in total p38, and increase in phospho-ERK1/2 thereby implying a role of differential modulation of MAPKs. Taken together, the results demonstrate that corn mint leaf components cause potent anti-inflammatory, anti-oxidant, and anti–infection effects in AMs via suppression of the production of cytokines/soluble mediators and ROS and increased pathogen clearance, respectively. To our knowledge, this is the first report on the mode of action of corn mint targeting the alveolar macrophages and on the potential role of MAPKs in immunomodulation by this product.