ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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
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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.
Subject(s)
Humans , Caprifoliaceae , Chemistry , Correlation of Data , Medicine, Tibetan Traditional , Molecular Docking Simulation , Receptors, G-Protein-Coupled , Metabolism , TasteABSTRACT
The theory on the property of Chinese materia medica (CMM) is one of the core contents of CMM theory, among which five flavors theory is the core content of CMM theory. The objective characterization of the five flavors of CMM is the key to the theoretical study of CMM, which is an important way to explain the scientific connotation of CMM. Based on the basic definition of five tastes medicinal properties and the interaction of drug molecules-taste, olfactory receptors, authors put forward the research methods using molecular docking technology and the research approach. In this study, the expression of five tastes drug property was systematically discussed from the aspects of biological mechanisms of taste, olfactory perception, molecular docking, homology modeling, and receptor selection, which provides a reference method for the study of drug property theory from the perspective of taste and smell attribute of five tastes.
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Objective@#To investigate the role of sweet taste receptors(STRs)in the activation of reactive oxygen species (ROS)-NLRP3 inflammasome signaling in diabetic kidney disease(DKD).@*Methods@#DKD mouse were established by high-fat diet and streptozotocin. After mouse glomerular mesangial cells(GMCs)were exposed to high glucose, STRs(T1R2/T1R3)and associated signaling components and NLRP3 inflammasome signaling components expressions were detected. After GMCs were treated with STRs inhibitor lactisole, the production of ROS was detected and the role of STRs in the activation of NLRP3 signaling was investigated.@*Results@#Under high glucose condition, the expressions of T1R2, T1R3, Gα-gustducin, phospholipase C-β2, and TRPM5 were significantly decreased in vivo and in vitro(all P<0.05)and ROS-NLRP3 signaling was activated(all P<0.05). Lactisole significantly mitigated the production of ROS and the activation of NLRP3 inflammasome signaling stimulated by high glucose in GMCs(all P<0.05).@*Conclusion@#The STRs(T1R2/T1R3)-mediated signaling pathway may be involved in the regulation of ROS-NLRP3 inflammatory signaling, suggesting that STRs may act as new therapeutic targets of DKD. (Chin J Endocrinol Metab, 2018, 34: 587-593)
ABSTRACT
Abstract Taste perception plays a key role in determining individual food preferences and dietary habits and may influence nutritional status. This study aimed to investigate the association of TAS1R2 (Ile191Val - rs35874116) and TAS1R3 (-1266 C/T - rs35744813) variants with food intake and nutritional status in children followed from birth until 7.7 years old. The nutritional status and food intake data of 312 children were collected at three developmental stages (1, 3.9 and 7.7 years old). DNA was extracted from blood samples and the polymorphisms were analyzed by real-time polymerase chain reactions (qPCR) using hydrolysis probes as the detection method. Food intake and nutritional status were compared among individuals with different single nucleotide polymorphism (SNP) genotypes. At 3.9 years old, children homozygous (Val/Val) for the TAS1R2 Ile191Val polymorphism ingested less sugar and sugar-dense foods than children who were *Ile carriers. This finding demonstrated that a genetic variant of the T1R2 taste receptor is associated with the intake of different amounts of high sugar-content foods in childhood. This association may provide new perspectives for studying dietary patterns and nutritional status in childhood.
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The tongue has 4 kinds of papillae, which are filiform, fungiform (FU), foliate (FO) and circumvallate papilla (CV). Tongue papillae except filiform papilla include taste buds. The papillae differ in taste sensitivities, likely due to differential expression of taste receptors. In this study, we evaluated differences in the expression levels of taste receptors in FU, FO and CV. Male DBA2 mice, 42-60 days old, were used in the study. Messenger RNAs were extracted from the murine epithelial tissues including FU, FO and CV. Cloned DNAs were synthesized by reverse transcription. Quantitative PCRs (qPCRs) were performed to determine mRNA expression levels of taste receptors. Results of qPCR revealed that the relative expression levels and patterns were different among FU, FO and CV. All three type 1 taste receptors were expressed FU, FO and CV at varying relative expression levels. All 35 kinds of type 2 taste receptors showed higher expression in FO and CV than in FU. Tas2r108 and Tas2r137 showed the two highest expression levels in all tested papillae. The differential expression levels and patterns of taste receptors among the three papillae could contribute to the different physiological sensitivities by tongue areas. Additional studies such as in situ hybridization or taste receptor cell activity recording is necessary to elucidate the functional relationship between expression levels of taste receptors and taste sensitivity.
Subject(s)
Animals , Humans , Male , Mice , Clone Cells , DNA , In Situ Hybridization , Mice, Inbred DBA , Polymerase Chain Reaction , Reverse Transcription , RNA, Messenger , Taste Buds , TongueABSTRACT
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.
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The distribution of the isozymes of α-glucosidase in different parts of Drosophila melanogaster was examined. Two of the eight glucosidase bands are associated with tarsi. The gustatory mutations in the genes gustB and gustC greatly reduce tarsal glucosidase activity, but the enzyme deficiency is not correlated with inability to taste sugars.