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.

Anti-inflammatory effects of volatile oils of Desmodium styracifolium via regulation of TRP channels / 中草药

Objective To screen out the key chemical constituents and target protein of essential oil of Desmodium styracifolium for its anti-inflammatory effect. Methods Steam distillation method was used to extract the volatile oils from D. styraci folium, and its chemical constituents were identified by GC-MS, and the relative content of chemical constituents was determined by peak area normalization. The small molecule ligand library was established based on Traditional Chinese Medicine Systems Pharmacology (TCMSP). Reverse target prediction was conducted online using Swiss Target Prediction, the anti-inflammatory pathways were screened by KOBAX 3.0, conducting energy match between the key small molecular and the target protein in the TRP channels by molecular docking (SYBYL2.1). Construction of chemical constituents-targets network model was based on Cytoscape 3.5.1. Results A total of 48 chromatographic peaks were detected from D. styracifolium volatile oils, and 33 kinds of compound structure were determined by searching in mass spectral database and document retrieval, which account for 90.1% of total volatile oils. There were 17 key chemical constituents, and 88 target proteins were selected. TRP channels included 11 potential targets. Through molecular docking, we found that the phytol, hentriacontane, farnesyl acetone, and squalene were the key anti-inflammatory chemical constituents of D. styraci folium volatile oils. TPRV1 (transient receptor potential cation channel, subfamily V, member 1), PRKCB (protein kinase C, beta), and PRKCD (protein kinase C, delta) (degree > 10) are the key anti-inflammatory target protein. Conclusion We preliminarily select the key anti-inflammatory target and active constituents of D. styraci folium volatile oils from this study, and this research provides the theoretical basis for the development and application of its products.

Food Intake and Thermogenesis in Adipose Tissue

Brown adipose tissue (BAT) is regarded as a key target for developing interventions to prevent and treat obesity and age-related diseases. In addition, uncoupling pro tein 1 (UCP1)

01-1 Molecular mechanisms of thermosensation through TRP channels / 日本温泉気候物理医学会雑誌

  TRP (transient receptor potential) channels were first described in Drosophila in 1989, and in mammals, TRP channels comprise six related protein families (TRPC, TRPV, TRPM, TRPA, TRPML, TRPP). One subunit of the TRP channel is composed of six transmembrane domains and a putative pore region with both amino and carboxyl termini on the cytosolic side. It is thought that the subunits form functional channels as homo- or hetero-tetramers. TRP channels are best recognized for their contributions to sensory transduction, responding to temperature, nociceptive stimuli, touch, osmolarity, pheromones and other stimuli from both within and outside the cell. Among the huge TRP super family of ion channels, some have been proven to be involved in thermosensation detecting ambient temperatures from cold to hot. There are now ten thermosensitive TRP channels (TRPV1, TRPV2, TRPV3, TRPV4, TRPM2, TRPM3, TRPM4, TRPM5, TRPM8 and TRPA1) with distinct temperature thresholds for their activation. Because temperature ranges above 43 degree C or below 15 degree C are considered to cause pain sensation in our body, thermosensitive TRP channels whose temperature thresholds are in the range can be viewed as nocicpetive receptors as well. Thermosensitive TRP channels work as ‘multimodal receptors’ which respond to various chemical and physical stimuli. TRPV1, the first identified thermosensitive TRP channel, was found as a receptor for capsaicin, and later was found to have thermosensitivity. I would like to talk about the physiological significance of the thermosensitive TRP channels (TRPV1, TRPA1, TRPV4 and TRPM2). Some of the thermosensitive TRP channels are expressed in the tissues not exposed to the dynamic changes in the ambient temperature and activated by warm temperature around our body temperature, suggesting that they have some specific physiological functuions. In addition, how structure and functions of thermosensitive TRP channels were changed dynamically in the process of evolution will also be discussed.

01-1Molecular mechanisms of thermosensation through TRP channels / 日本温泉気候物理医学会雑誌

  TRP (transient receptor potential) channels were first described in Drosophila in 1989, and in mammals, TRP channels comprise six related protein families (TRPC, TRPV, TRPM, TRPA, TRPML, TRPP). One subunit of the TRP channel is composed of six transmembrane domains and a putative pore region with both amino and carboxyl termini on the cytosolic side. It is thought that the subunits form functional channels as homo- or hetero-tetramers. TRP channels are best recognized for their contributions to sensory transduction, responding to temperature, nociceptive stimuli, touch, osmolarity, pheromones and other stimuli from both within and outside the cell. Among the huge TRP super family of ion channels, some have been proven to be involved in thermosensation detecting ambient temperatures from cold to hot. There are now ten thermosensitive TRP channels (TRPV1, TRPV2, TRPV3, TRPV4, TRPM2, TRPM3, TRPM4, TRPM5, TRPM8 and TRPA1) with distinct temperature thresholds for their activation. Because temperature ranges above 43 degree C or below 15 degree C are considered to cause pain sensation in our body, thermosensitive TRP channels whose temperature thresholds are in the range can be viewed as nocicpetive receptors as well. Thermosensitive TRP channels work as ‘multimodal receptors’ which respond to various chemical and physical stimuli. TRPV1, the first identified thermosensitive TRP channel, was found as a receptor for capsaicin, and later was found to have thermosensitivity. I would like to talk about the physiological significance of the thermosensitive TRP channels (TRPV1, TRPA1, TRPV4 and TRPM2). Some of the thermosensitive TRP channels are expressed in the tissues not exposed to the dynamic changes in the ambient temperature and activated by warm temperature around our body temperature, suggesting that they have some specific physiological functuions. In addition, how structure and functions of thermosensitive TRP channels were changed dynamically in the process of evolution will also be discussed.

TRP channels, omega-3 fatty acids, and oxidative stress in neurodegeneration: from the cell membrane to intracellular cross-links

The transient receptor potential channels family (TRP channels) is a relatively new group of cation channels that modulate a large range of physiological mechanisms. In the nervous system, the functions of TRP channels have been associated with thermosensation, pain transduction, neurotransmitter release, and redox signaling, among others. However, they have also been extensively correlated with the pathogenesis of several innate and acquired diseases. On the other hand, the omega-3 polyunsaturated fatty acids (n-3 fatty acids) have also been associated with several processes that seem to counterbalance or to contribute to the function of several TRPs. In this short review, we discuss some of the remarkable new findings in this field. We also review the possible roles played by n-3 fatty acids in cell signaling that can both control or be controlled by TRP channels in neurodegenerative processes, as well as both the direct and indirect actions of n-3 fatty acids on TRP channels.

Immunohistochemical Study on the Distribution of Canonical Transient Receptor Potential Channels in Rat Cerebellum / 체질인류학회지

Channels formed by the transient receptor potential (TRP) family of proteins have a variety of physiological functions. In the present study, we examined the localization of canonical transient receptor potential channels (TRPCs) in rat cerebellum. Twelve adult (4~6 month old) Sprague-Dawley rats were examined in this study. We performed immunohistochemistry using specific antibodies against TRPCs to investigate the detailed and comparative distribution of six TRPCs in rat cerebellum. There was a high density of TRPC1, TRPC3, TRPC4, TRPC5 and TRPC7, with a much lower density of TRPC6 in the rat cerebellar cortex. The somatodendritic Purkinje cell areas were intensely stained with antiTRPC3, TRPC4, TRPC5 or TRPC7 antibodies, whereas the staining intensity of TRPC6 was relatively low in the Purkinje cell bodies. In the cerebellar nuclei, the cell bodies of cerebellar output neurons showed moderate TRPC1, TRPC3, TRPC5 and TRPC7 immunoreactivities, while TRPC6 immunoreactivity was observed in the surrounding neuropil. This study showing the differential localizations of TRPC channels in the cerebellum may provide useful data for the future investigations on the structural and functional properties of TRPCs.