Anti-Inflammatory and Analgesic Properties of Pulegone, a Major Component in Calamintha Nepeta

Abstract Monoterpenes are small molecules, composed of two isoprene units, able to pass through the blood brain barrier, allowing to target both peripheral and central pain pathways. They are the main components of essential oils, responsible for their diverse well-known biological activities. Menthol, the main monoterpene found in Mentha piperita (L.) is known to modulate nociceptive threshold and is present in different curative preparations that reduces sensory hypersensitivities in pain conditions. While pulegone is a menthol-like monoterpene, only a limited number of studies focuses on its putative analgesic effects. Pulegone is the most abundant monoterpene presents in Calamintha nepeta (L.), a Laminaceae plant used in traditional medicine to alleviate rheumatic disorders, a chronic inflammatory disease. Here, we compared the impacts of menthol and pulegone on pain and inflammation. First, we described that both monoterpenes are anti-inflammatory compounds. Secondly, we found that while menthol is highly cytotoxic at anti-inflammatory concentrations, the cytotoxic effects of pulegone are limited, if not absent. Finally, in a model of peripheral inflammatory-induced pain a pulegone treatment exerts a significantly higher anti-hyperalgesic effect than menthol in response to mechanical stimuli, heat and cold thermal stimulations than a menthol treatment. In conclusion we demonstrated that pulegone is an anti-inflammatory compound and it is acting a potent pain-killer in acute inflammatory pain condition.