Baicalin Promotes the Apoptosis of Respiratory Inflammatory Cells in Asthmatic Mice through Bitter Taste Receptors / 中国生物化学与分子生物学报

Asthma is a heterogeneous disease that affects three hundred million people worldwide. About half of them are not well controlled, new therapeutic approach and more effective medicines are therefore urgently needed. Recent studies have shown that bitter taste receptors (Tas2rs) are expressed in respiratory system, and Tas2rs might be used as new targets for asthma treatment since some bitter compounds show therapeutic potential for asthma therapies. Based on this situation, we studied the effect of bitter compound baicalin (BA) on the apoptosis of inflammatory cells in the respiratory tract of asthmatic mice and its relationship with bitter signal transduction. Male BALB/c mice were selected as the tested animals randomly divided into control group (CK), asthma mouse model group stimulated by intraperitoneal injection and aerosol inhalation of ovalbumin(OVA) and intragastric administration of BA intervention OVA-induced asthma group (OVA + BA). The results showed that inflammatory cells infiltration, alveolar septum thickening and diminished alveolarspaces were observed in the OVA group after HE staining. The above symptoms were significantly alleviated in OVA+BA group. The total number of inflammatory cells and classified cell count in the bronchoalveolar lavage fluid of mice in OVA group were increased, and the number of inflammatory cells in BA intervention group were decreased significantly (P < 0. 05). Analysis of real-time quantitative PCR showed that the expression levels of mucin Muc5ac were significantly increased in the lung in OVA group (P <0. 05), while the expression levels of Muc5ac in OVA+BA group were significantly lower than that in OVA group (P <0. 05). The expression of Tas2r108, Tas2r126, Tas2r135, Tas2r143 and their downstream signal transduction molecules α-gust and Trpm5 were down-regulated in OVA group (P < 0. 05). In OVA group, the transcription of pro-apoptotic factors P53, Bax and Casp3 was inhibited, and decreased activity of caspase3 was detected, whereas the transcription of anti-apoptotic factor Bcl2 was up-regulated (P < 0. 05). In OVA+BA group, the transcription of tested Tas2rs genes and downstream signal transduction molecules (P < 0. 05), as well as pro-apoptotic genes P53, Bax and Casp3 were all up-regulated associated with the decreased Bcl2 expression and increased caspase3 activity (P < 0. 05). Our results suggest that BA might function as a bitter taste receptor agonist to mediate the regulation of respiratory tract inflammatory cells apoptosis by activating the bitter signal transduction system, and thus to reduce the lung inflammation and injury in asthmatic mice.

Mechanism of Combination of Pungent Dispersing Bitter Evacuant in Treatment of Asthma Based on Theory of Five Flavor Compatibility / 中国实验方剂学杂志

Bronchial asthma， a chronic inflammatory airway disease， belongs to the category of wheezing disease in the system of traditional Chinese medicine （TCM）. The wheezing symptom of this disease is mainly caused by the imbalance of lung Qi. According to the theory of five flavor compatibility， the Chinese medicinal materials with five different flavors （pungent， bitter， sour， sweet， and salty） can be combined to produce new functions. The pungent medicinal materials have dispersing effect and the bitter medicinal materials have discharging effect， which are important components in the theory of five flavor compatibility. Pungent herbs and bitter herbs can relieve the adverse lung Qi， occupying an important position in the current medication for the treatment of asthma. However， there is still a lack of in-depth analysis of the TCM theory and mechanism of the compatibility of pungent herbs and bitter herbs in the treatment of asthma. The molecular mechanisms of action of pungent herbs and bitter herbs are closely related to transient receptor potential （TRP） channels and bitter taste receptors （TAS2Rs）， respectively. Ca2+ signaling has been recognized in the process of asthma and is involved in the development of multiple symptoms of asthma. The TRP channels and TAS2Rs located on the cell membrane have been proved to directly regulate the intracellular Ca2+ signal and play a role in the treatment of asthma. Therefore， the dispersing effect of pungent herbs and the discharging effect of bitter herbs may be realized through the Ca2+ signaling pathway mediated by TRPs/TAS2Rs. We summarized the theoretical understanding and modern studies of pungent herbs dispersing lung Qi and bitter herbs discharging lung Qi， aiming to explain the internal relationship and mechanism of the compatibility of pungent herbs and bitter herbs in the treatment of asthma from the perspective of TCM theory and modern medicine. The compatibility of pungent herbs and bitter herbs based on the theory of five flavor compatibility for the treatment of asthma has a solid theoretical basis of TCM， and its mechanism can be verified by modern research. Therefore， it may be a main research direction in the treatment of asthma by Chinese medicinal herbs in the future.

Inhibition of Respiratory Bitter Taste Signal Transduction is Related to Asthma in Mice / 中国生物化学与分子生物学报

Because the large number of people is suffering from asthma, and about half of them are not well controlled, new therapeutic approach and more effective medicines are therefore urgently needed. Recent studies have shown that bitter taste receptors (T2Rs) are expressed in various tissues, and T2Rs might be used as the new targets for asthma treatment since some bitter compounds show therapeutic potential for asthma therapies. In this study, the relationship between the development and exacerbation of asthma and bitter signal transduction was analyzed by establishing the asthma model in the C57BL/6 mice. The present results showed that the total number of white blood cells and the number of eosinophil, neutrophil, lymphocyte and macrophages in the bronchoalveolar lavage fluid (BALF) were significantly increased (P < 0. 05), accompanied with the up-regulation of Muc5ac gene expression (P< 0. 01) and asthma-like pathologically changes in mice lungs in OVA or OVA+SO

Correlation study on Tibetan medicine Pterocephalus hookeri of bitter taste receptors based on molecular docking technology / 中国中药杂志

In order to study the interaction between Pterocephalus hookeri and bitter taste receptors,three-dimensional structural models of bitter taste receptors TAS2 R16,TAS2 R14 and TAS2 R13 were established by homology modeling in this paper. Maestro software was used for docking the chemical constituents of P. hookeri with bitter taste receptors. The results showed that 25 chemical components of P. hookeri can regulate three bitter taste receptors. And these components were mainly iridoid glycosides and phenolic acids.This research focused on the comprehensive application of homology modeling and molecular docking technology to explore the interaction between bitter chemical constituents of P. hookeri and bitter taste receptors. This study provided assistance in revealing pharmacodynamic basis of bitter Tibetan medicine at molecular level. It also provided new ideas and methods for the study of Tibetan medicine.

Study on Modern Scientific Connotation of Bitter Taste Property of Chinese Materia Medica Based on Bitter Taste Receptors / 世界科学技术-中医药现代化

Bitter taste receptors (BTRs) belong to the G protein-coupled receptors, which included 25 subtypes. BTRs, which were distributed in the oral cavity, mediated the bitter taste of mammalian. Furthermore, BTRs were also existed in the extra-oral digestive system such as the stomach and intestine to influence the digestion, absorption and energy regulation. It also can relax airway smooth muscles in the respiratory system and decrease blood pressure in the cardiovascular system. While being strikingly conformed to the latest advancements of BTRs, the efficacy of bitter taste property of Chinese materia medica (CMM) such as“excretion”,“dryness” and“strengthening” have been used in ancient theories of property and flavor in traditional Chinese medicine (TCM) for thousands of years in the treatment of multisystem diseases such as digestive, endocrine, respiratory and cardiovascular system. Therefore, applying modern techniques and new methods in the interpretation of the scientific connotation of bitter taste property of CMM based on BTRs should be a feasible way and a new research pattern. It played an important role in the enriching of the property theory in CMM, as well as enhancing the modernization and objectivization of CMM.