Abstract
Significant advances have been made in the past decade in mapping the distributions and the physiological functions of extra-oral bitter taste receptors (TAS2Rs) in non-gustatory tissues. In particular, it has been found that TAS2Rs are expressed in various muscle tissues and activation of TAS2Rs can lead to muscle cell relaxation, which suggests that TAS2Rs may be important new targets in muscle relaxation therapy for various muscle-related diseases. So far, however, there is a lack of potent extra-oral TAS2R agonists that can be used as novel drug agents in muscle relaxation therapies. Interestingly, traditional Chinese medicine (TCM) often characterizes a drug’s property in terms of five distinct flavors (bitter, sweet, sour, salty, and pungent) according to its taste and function, and commonly regards “bitterness” as an intrinsic property of “good medicine.” In addition, many bitter flavored TCM are known in practice to cause muscle relaxation after long term use, and in lab experiments the compounds identified from some bitter flavored TCM do activate TAS2Rs and thus relax muscle cells. Therefore, it is highly possible to discover very useful extra-oral TAS2R agonists for muscle relaxation therapies among the abundant bitter compounds used in bitter flavored TCM. With this perspective, we reviewed in literature the distribution of TAS2Rs in different muscle systems with a focus on the map of bitter flavored TCM which can regulate muscle contractility and related functional chemical components. We also reviewed the recently established databases of TCM chemical components and the bioinformatics software which can be used for high-throughput screening and data mining of the chemical components associated with bitter flavored TCM. All together, we aim to present a knowledge-based approach and technological platform for identification or discovery of extra-oral TAS2R agonists that can be used as novel drug agents for muscle relaxation therapies through screening and evaluation of chemical compounds used in bitter flavored TCM.
Highlights
Humans can distinguish five basic taste modalities including bitter, sweet, sour, salty, and umami, classified by modern science, which forms the principal gustatory perception often experienced during food consumption (Drewnowski and Gomez-Carneros, 2000; Meyerhof, 2005)
Here, we reviewed the recent advances in the understanding about the structure, distribution and function of TAS2Rs in diverse muscle tissues, with highlights of the perceptive profile of TAS2Rs for bitter components from bitter flavored traditional Chinese medicine (TCM)
We reviewed the bitter flavored TCM that are already used in treatment of muscle related symptoms in cardiovascular, respiratory, gastrointestinal, bladder, and uterus systems
Summary
Humans can distinguish five basic taste modalities including bitter, sweet, sour, salty, and umami, classified by modern science, which forms the principal gustatory perception often experienced during food consumption (Drewnowski and Gomez-Carneros, 2000; Meyerhof, 2005). Traditional Chinese medicine (TCM), developed over 1000 of years based on experience of fighting diseases, has established a “Flavor Theory” that categorizes the medicinal materials into similar “five flavors” including bitter, sweet, sour, salty, and pungent, according to the material’s taste and function (Hesketh and Zhu, 1997; Lukman et al, 2007; Ma et al, 2013; Zhang et al, 2016; Dragos and Gilca, 2018). It is strongly believed and apparently supported by empirical evidences in TCM that “Good medicine tastes bitter” (Lu et al, 2017). There has been a vast source of chemical compounds identified from bitter flavored TCM but their functional targets remain to be identified, which undoubtedly provides a gold mine for searching potential good drugs for treating various diseases (Editorial, 2007; Cheung, 2011)
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