On cool, how can nutmeg beat mint?

In addition to the taste of sour, sweet, bitter, spicy and salty, there is also a very strange feeling that is cold The cool taste can not only produce a cool feeling on the mouth, but also on the skin Whether it's human mouth or skin, are full of cold sensors that can transmit cool feeling, they are receptors of cool feeling Menthol is the most common cooling agent It can activate the TRPM8 ion channel, so people will feel cool when they wash their mouth with the mouthwash containing menthol Recently, the Tomohiro Shirai team of the Japanese flower king extracted a new lignan compound from nutmeg, which is more "cold" The molecular mechanism of the cooling sensation of nutmeg (source: Chemical & Engineering News) is on the cell membrane on the surface of human cells, there are TRP ion channels (transient receptor potential ion channels), which are usually closed, but can be opened by a certain intensity of stimulation, allowing cations to enter the cells These strong stimuli include strong mechanical force, large changes in pH value, large changes in temperature, chemicals that can combine with TRP channels, etc There are about 28 kinds of TRP ion channels, which can be divided into seven categories: TRPC (canonical), trpv (vanilloid), trpa (ankyrin), TRPM (melastatin), trpp (polycystin), trpml (mucolipin) and TRPN (nompc) Each category has several kinds For example, if flies have two kinds of trpv ion channels, there are six kinds in mice and humans, TRPV1, TRPV2, tr Pv3, TRPV4, TRPV5 and TRPV6 Animal experiments show that TRPV1 is the most important for nociceptive stimulation At temperatures below 17 degrees Celsius, the TRPA1 ion channel is activated to report low temperatures to the body When the temperature is lower, the TRPM8 ion channel is activated to report possible frost damage to the body Menthol can be combined with TRPA1 and TRPM8 ion channels to activate them, making us feel cold, although the actual temperature has not decreased Commercial 8 kinds of cooling agents (source: Chem station) the most common cooling agent menthol the most common cooling agent is menthol, also known as menthol It has a cool, sweet and light Mint characteristic fragrance It is the main component of peppermint essential oil, colorless needle crystal or granular Menthol has long been known as the king of cooling compounds and has been widely added to medicines, daily necessities and food However, menthol has some disadvantages: for example, when the concentration is low, its action time is short; if the concentration is too high, it will cause instant strong stimulation; moreover, menthol is volatile and not resistant to high temperature, so its use in some foods requiring high temperature treatment is limited In order to overcome the above shortcomings, since the 1960s, many chemists began to modify the structure of menthol and menthol or seek their alternative compounds to adapt to the requirements of different occasions After decades of research, hundreds of new flavor cooling agents have been synthesized, most of them are amide compounds Nutmeg neolignan (source: Chemical & Engineering News) is the most effective activator in the cooling channel so far In order to find a more durable and less irritating cooling agent from natural sources, chemists of king of Japan tested the activity of TRPM8 ion channel activated by natural products of thousands of plant drugs and spices After years of research, researchers finally isolated a new type of TRPM8 ion channel activator Neolignans from nutmeg The research results were published on ACS medical chemistry letters under the title of identification of a new TRPM8 agent from nutmeg: a promising cooling compound The researchers found that the new compounds produce about 30 times the chilling sensation of menthol, almost as effective as synthetic coolant icilin, and that their binding site with TRPM8 is different from menthol, which means that if they are mixed in menthol products, the combination of the two will have a superposition effect, rather than competing sites In the cold sensation duration test, researchers rinsed the mouth with a solution of the new compound for 30 seconds and evaluated its cooling effect within half an hour It took five minutes for the new compounds to reach the initial chilling level of menthol, but the chilling effect lasted for 30 minutes, 1.5 times that of menthol John C Leffingwell, President of Leffingwell & Associates, commented that as the content of new lignans in nutmeg is very small, and there is not enough economic full synthesis or semi synthesis method, the way to market is still very long Paper link: http://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.7b00104? Source = Cen http://embomolmed.embopress.org/content/early/2017/04/10/emmm.201607300.long