In silico investigation of the association of the TRPM8 ion channel with the pungent flavor of Chinese herbs

Objective:Explicating the property and action of traditional Chinese medicine(TCM)in the perspectives of modern science deepens the insight into the property of TCM,and provides the basis for new drug discovery and clinical therapy.In this study,we investigated the relationship between transient receptor potential melastatin 8(TRPM8)and pungent flavor using three-dimensional pharmacophores based on virtual screening methods.Methods:Firstly,an inhouse database was established to identify the related pharmacological action according to the traditional Chinese herbs expressing an action of promoting blood circulation.Then,several therapeutic targets,3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMG-CoAR),cholesteryl ester transfer protein(CETP),Niemann-Pick C1-Like 1(NPC1L1)and platelet-activating factor receptor(PAFR),were selected to screen traditional Chinese herbs,and the common virtual screening hits with various hit scores providing data to reveal the correlation among TRPM8 and therapeutic targets.Results:According to the screening results,TRPM8 agonists were able to identify the effective components of pungent herbs and TRPM8,which shares the common virtual screening hits with the therapeutic targets,was considered to be related to the action of pungent taste.Conclusion:The novel ideas and methods in this study are beneficial to unveil the scientific relationship between a TCM property and its action.

From ancient wisdom to modern science:Gut microbiota sheds light on property theory of traditional Chinese medicine

The property theory of traditional Chinese medicine(TCM) has been practiced for thousands of years,playing a pivotal role in the clinical application of TCM. While advancements in energy metabolism,chemical composition analysis, machine learning, ion current modeling, and supercritical fluid technology have provided valuable insight into how aspects of TCM property theory may be measured, these studies only capture specific aspects of TCM property theory in isolation, overlooking the holistic perspective inherent in TCM. To systematically investigate the modern interpretation of the TCM property theory from multidimensional perspectives, we consulted the Chinese Pharmacopoeia(2020 edition) to compile a list of Chinese materia medica(CMM). Then, using the Latin names of each CMM and gut microbiota as keywords, we searched the PubMed database for relevant research on gut microbiota and CMM. The regulatory patterns of different herbs on gut microbiota were then summarized from the perspectives of the four natures, the five flavors and the meridian tropism. In terms of the four natures, we found that warm-natured medicines promoted the colonization of specific beneficial bacteria,while cold-natured medicines boosted populations of some beneficial bacteria while suppressing pathogenic bacteria. Analysis of the five flavors revealed that sweet-flavored and bitter-flavored CMMs positively influenced beneficial bacteria while inhibiting harmful bacteria. CMMs with different meridian tropism exhibited complex modulative patterns on gut microbiota, with Jueyin(Liver) and Taiyin(Lung) meridian CMMs generally exerting a stronger effect. The gut microbiota may be a biological indicator for characterizing the TCM property theory, which not only enhances our understanding of classic TCM theory but also contributes to its scientific advancement and application in healthcare.

Information integration research on cumulative effect of 'Siqi,Wuwei,and Guijing' in Traditional Chinese Medicine

OBJECTIVE:To study the morphological basis of the role of Siqi(cold as winter,cool as autumn,warm as spring,hot as summer),Wuwei(five flavors:sweet,pungent,salty,sour,and bitter),and Guijing(meridian tropism) through the use of information integration.METHODS:A14C-2-deoxy-glucose autoradiography method was adopted to determine the overall impact of treatment with 39 herbs on functions of various tissues and organs.Data was measured at 4hs after a single dose and following the last treatment of repeated doses for a week.Least-squares estimation was used and fitted for each herb regression effect of organs and tissues after singleand repeated treatment.The slope of the regression line represented the cumulative trend of the effect of the herbs(β),and the standard deviation of the slope(Sβ) was compared with those of the untreated animals(t 'test).All significantly cumulative effect trends were applied with an artificial neural network,which integrated the relationship among Siqi,Wuwei,and Guijing with tissues and organs.RESULTS:There is a certain relationship among the Siqi,Wuwei,Guijing and the anatomy of organs and tissues,but the different scores indicate that influence of Siqi,Wuwei,Guijing to anatomy of organs and tissues was a nonlinear state.CONCLUSION:Results demonstrated that the effects of Siqi,Wuwei,and Guijing have a morphological basis,and each concept was associated with multiple anatomical structures.