The rise in obesity and inflammatory diseases is adding to the increase in lifestyle disorders like diabetes and hypertension. There is a need for natural remedies to address these issues. Scientists have created new forms of menthol using amino acids and examined their effects. The menthyl esters displayed significant anti-inflammatory and anti-obesity properties in early studies and could serve as potential therapeutic agents with more research.Lifestyle disorders like diabetes and hypertension are difficult to treat with natural remedies. However, researchers at Tokyo University of Science have created new amino acid derivatives of menthol and examined their properties. The menthyl esters demonstrated strong anti-inflammatory and anti-obesity effects in preclinical studies, suggesting potential for further development as therapeutic compounds. This shows that modifying natural products can lead to important medical breakthroughs and commercial success. Menthol, a natural cyclic monoterpene alcohol, has been especially promising in this regard.Menthol is commonly found in a variety of plants, especially in the mint family like peppermint and spearmint. It is a popular ingredient in many candies, chewing gums, and oral care products. Notably, menthol also has significant medicinal properties because of its ability to relieve pain, reduce inflammation, and potentially fight cancer.
In a recent research study, Professor Gen-ichiro Arimura and his team from the Department of Biological Science and Technology at Tokyo University of Science in Japan, developed and studied menthyl esters of valine (MV) and isoleucine (MI), which are compounds derived from menthol by replacing its hydroxyl group.The researchers published their findings in the Immunology journal on May 08, 2024. Prof. Arimura shared that the motivation behind the work was the discovery of new molecules from natural materials, which inspired the research team to develop amino acid derivatives of menthol. They started by creating menthyl esters of six amino acids with less-reactive side chains and then studied the properties of these esters using in vitro cell line studies.The researchers performed tests on mice to see how these compounds affected them when they had induced diseases. They found that MV and MI had strong anti-inflammatory effects by looking at the levels of tumor necrosis factor-α (Tnf) in stimulated macrophage cells. Surprisingly, both MV and MI performed better than menthol in the anti-inflammatory test. They also found that 18 genes related to inflammation and immune responses were effectively suppressed, as shown by RNA sequencing analysis.
Excited by their results, the researchers delved deeper into how the menthyl esters worked. They found that the compounds targeted the liver X receptor (LXR), which is a key regulator of inflammatory responses. This discovery sheds light on the mechanisms behind the anti-inflammatory effects of MV and MI.The intracellular nuclear receptor LXR (LXR) plays a crucial role in anti-inflammatory effects, separate from the cold-sensitive transient receptor TRPM8, which is primarily responsible for detecting menthol. Further research into the LXR-dependent activation of MV and MI revealed that the Scd1 gene, which is central to lipid metabolism, is upregulated by LXR. Additionally, in mice with induced intestinal colitis, the anti-inflammatory effects were confirmed through suppressed transcript levels of Tnf and Il6 genes by MV or MI in an LXR-dependent manner.
Building on the discovery of the LXR-SCD1 intracellular machinery, Professor Arimura and his team sought to understand the mechanisms at play.The researchers suggested that menthyl esters may have properties that can help with obesity. They discovered that these esters stopped fat accumulation, especially during the mitotic clonal expansion stage in 3T3-L1 adipocyte cells. In animal studies, they also found that menthyl esters improved diet-induced obesity in mice and suppressed fat accumulation.
Menthyl esters have advantages over other compounds being studied or used for inflammation and obesity. Their specific mechanisms of action contribute to both anti-inflammatory and anti-obesity effects, making them stand out from other compounds and potentially very effective.The study highlights the significance of targeting inflammatory conditions and metabolic disorders for potential therapeutic benefits. Specifically, it suggests that certain compounds could be beneficial for individuals with chronic inflammatory conditions, metabolic syndrome, or obesity-related complications. Professor Arimura also expresses optimism that these compounds may be effective in addressing lifestyle-related diseases such as diabetes, hypertension, and allergic symptoms.The value of complex molecules derived from natural substances is being explored. Research on these new and improved menthyl esters may lead to the development of therapeutic compounds to address the growing health concerns related to obesity and inflammatory conditions.
