Molecular mechanisms of Tibetan medicine Sug-Mel-sum-thang in treating insomnia disorder:network pharmacology,molecular docking,and surface plasmon resonance

Background:The Tibetan medicine Sug-Mel-sum-thang(SMST)is often used to treat insomnia disorder(ID);however,the underlying mechanism remains unclear.In this study,network pharmacology prediction was conducted to analyze the molecular mechanisms of SMST in treating ID.Methods:The active ingredients of the three herbs used in SMST were obtained from the Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences.Chemistry Database[DB/OL].The chemical formulae of the active ingredients were downloaded from PubChem in canonical SMILES format.These were then imported into the SwissTargetPrediction platform to identify drug targets.ID targets were obtained from databases such as DrugBank,GeneCards,and DisGeNET.Potential targets of SMST for the treatment of ID were identified using the online Venny mapping platform.The potential target protein-protein interaction was constructed using the STRING platform,and the obtained protein-protein interaction information was imported into Cytoscape 3.7.1 for image optimization and core gene extraction and ClueGO in Cytoscape 3.7.1 was used for the enrichment analysis of potential targets.Cytoscape 3.7.1 was also used to construct the regulatory network of the Tibetan medicine compound target pathway and conduct a topological analysis.Results:The mechanism of action of SMST in the treatment of ID involved 72 compounds,including nerolidol,apigenin,luteolin,and piperine.The key targets identified were COMT,CNR1,AKT1,SLC6A4,TNF,CTNNB1,and CHRNA4.The enrichment analysis obtained 69 KEGG pathways,mainly related to Alzheimer’s disease,cAMP signaling pathway,serotonergic synapse,and other pathways.The core active ingredient molecule docked with the target to a higher degree.The results showed that the active ingredient exhibited good binding activity with the related targets.Some parts with good docking fractions were selected for surface plasmon resonance analysis.Conclusion:Various active components in SMST play a role in the treatment of ID by acting on key targets,such as COMT and CNR1,to regulate multiple signaling pathways.

Compatibility Rules of Prescriptions of Tibetan Medicine Polygonatum cirrhifolium Based on Data Mining

[Objectives]To study the prescription compatibility rules of the Tibetan medicine Polygonatum cirrhifolium(Polygonati Rhizoma,Huangjing)based on data mining,so as to provide data support for clinical application and new drug development.[Methods]Prescriptions containing Tibetan medicine Huangjing were collected from Tibetan Medicine Prescriptions Encyclopedia and Tibetan Medicine Classic Literature Collection.The Traditional Chinese Medicine Inheritance Computing System(TCMICS 3.0)and R version 4.1.3 were used to mine and analyze the compatibility rules of prescriptions containing Tibetan medicinal material Huangjing,the rules of medication for high-frequency diseases,and the association rules of various medicinal materials.[Results]A total of 124 prescriptions were collected from the classic literature of Tibetan medicine,and the frequency statistical analysis showed that drugs compatible with Huangjing(≥15)included Tianmendong(Root of Cochinchinese Asparagus)(80),Mirabilis himalaica(Edgew.)Heimerl(Himalayan purple jasmine)(72),Jili(Tribuli Fructus)(70),Tibetan Aoruqin(Vicatia coniifolia)(58),Baidoukou(Round Cardamom Fruit)(47),Hezi(Chebulae Fructus)(45),Shouzhangshen(Rhizome of Conic Gymnadenia)(28),Yuganzi(Phyllanthi Fructus)(26),Pomegranate(25),Maohezi(Terminaliae Belliricae Fructus)(24),Zicaorong(Lacca)(23),Rougui(Cinnamomi Cortex)(15).The main diseases were yellow water disease(20),gynecological diseases(19),kidney cold disease(17),and other Tibetan medicine diseases.Association rule analysis showed that the drug combinations with the highest frequency were Huangjing—Tianmendong,Huangjing—Himalayan purple jasmine,and Huangjing—Jili.[Conclusions]The frequency of combined use of Tibetan medicine Huangjing with dry yellow water,tonifying kidney and diuresis,nourishing health,and treating gynecological diseases is relatively high.

A Review of Study of Yellow Water Disease in Tibetan Medicine Theory

Based on the Tibetan medical theory,the relevant information and diagnosis and treatment ideas of yellow water disease are discussed,and Mongolian medicine also takes its own basic medical theory as the starting point to discuss and explain,while traditional Chinese medicine has made less theoretical description of this disease,but there are also some understandings and treatment guidelines.This paper mainly discusses the cognitive aspects of this disease,starting from the essence,analyzes the relationship between this disease and traditional Chinese medicine diseases as well as modern medicine,and makes a theoretical description for a better understanding of the yellow water disease.

HPLC-based Activity Profiling of Anti-Hepatocellular Carcinoma Constituents from the Tibetan Medicine, Caragana tibetica

During the screening of a traditional Chinese folk herb library against Hep G2 and Hep3 B cell lines, the Et OAc extract from the Tibetan medicine, Caragana tibetica（CT-Et OAc） exhibited potential anti-hepatocellular carcinoma（anti-HCC） activity. HPLC-based activity profiling was performed for targeted identification of anti-HCC activity from CT-Et OAc by MS-directed purification method. CT-Et OAc was separated by time-based fractionation for further anti-HCC bioassay by a semipreparative HPLC column（150 mm × 10 mm i.d., 5 μm） with a single injection of 5 mg. Bioassay-guided and ESIMS-directed large scale purification was performed with a single injection of 400 mg of CT-Et OAc by peak-based fractionation. A 1.4-mm heavy wall micro NMR tube with z-gradient was used to measure one and two dimensional NMR spectra for the minor or trace amounts of components of the extract. Two active compounds could be elucidated as naringenin chalcone（CT-1） and 3-hydroxy-8, 9-dimethoxypterocarpan（CT-2） relevant to anti-HCC effects for the Et OAc extract of C. tibetica rapidly and unambiguously by this protocol.

Reliability and validity of the Tibetan medicine constitution scale: a cross-sectional study of the general population in Beijing, China

Background:The constitutional theory is an important aspect of Tibetan medicine,however a quantitative measurement tool for constitution identification still does not exist.The objective of this study is to evaluate the reliability and validity of a Tibetan medicine constitution scale(TMCS)that consists of three sub-scales and 31 items.Methods:From June to July 2019,622 people from the general population in Beijing,China,aged 18 to 60 were investigated.We employed Cronbach’s alpha(α),split-half reliability,and test-retest reliability to determine the reliability of the scale.The content validity and contract validity of the TMCS were evaluated using factor analysis and correlation analysis based on Tibetan medicine theory.The items were screened according to the reliability test results.Results:After the items were screened,22 items remained in the scale.The Cronbach’s alpha value for the internal consistency reliability of the TMCS was 0.754(95%confidence interval(CI):0.700–0.761).The correlation coefficient for the two-week test-retest of the total score was 0.726(95%CI:0.571–0.834).The split-half coefficient was 0.689(95%CI:0.640–0.734).The scale can be explained by eight potential factors,including morphological structure,physiological function,personality,adaptability,etc.The body mass index was negatively correlated with the score of the sub-rlung scale(r=−0.376),slightly positively correlated with the sub-mkhris pa scale(r=0.099),and positively correlated with the sub-bad kan scale(r=0.362).Conclusion:The TMCS is a reliable and valid instrument that can be used to assess the body constitution of the general population in Beijing,China.Future studies are needed to explore the differences in biological characteristics among the constitutional types and the association between constitution and disease.

Identify potential treatments of COVID-19 from Tibetan medicine Hippophae Fructus using a network pharmacological approach

OBJECTIVE Since the coronavirus disease 2019(COVID-19)outbreak in December 2019,the search for a potential treatment for COVID-19 has been a constant focus.Therefore,we identified potential treatments for COVID-19 from Hippophae Fructus,a Tibetan medicine that may act on COVID-19,using a network pharmacology approach.METHODS We collected the chemical constituents and corresponding targets of Hippophae Fructus from traditional Chinese medicine system pharmacology(TCMSP).COVID-19 related genes were predicted in pubmed-Gene,OMIM and GeneCards databases.Then,protein-protein interactions(PPIs)of key genes were analyzed by STRING database.Compound-target-diseases network was constructed using Cytoscape software.The potential pathways were determined by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses.Additionally,molecular docking was used to verify the binding effect between the active component and the target.RESULTS A total of 33 components and 192 corresponding targets in Hippophae Fructus were found.50 genes were obtained from the intersection of component targets and disease targets.These genes include IL-6,TNF,MAPK8 and PTGS2,which regulate several pathways associated with COVID-19,involving Hepatitis B,Influenza A,TNF signaling pathway and Tuberculosis.More importantly,high-node compounds such as quercetin and beta-sitosterol can well bind to key targets.CONCLUSION Some components in Hippophae Fructus can act on COVID-19 related genes and regulate multiple pathways.Perhaps Hippophae Fructus has the effect in treating COVID-19.

Research Progress of Copper-bearing Minerals in Tibetan Medicine

Copper mineral medicines are widely used in clinical practice.There are 11 kinds of copper-bearing minerals used in the treatment of diseases in Tibetan medicine:bjarosite,silane malachite,brass,malachite,turquoise,bronze,ring copper,turquoise,red copper,chlorite,copper.In this paper,the main components,processing methods,clinical uses and modern pharmacological research progress of copper-bearing minerals in Tibetan medicines were summarized by referring to the Tibetan medicine books,modern ethnic medicine monographs,current quality standards and recent literature,providing reference for the sustainable development and effective utilization of Tibetan medicine resources.

Exploring the Development Prospects of Tibetan Medicine

Tibetan medicine is a“bright pearl in the treasure house”of traditional ethnic medicine in China.It has the benefits of a complete and time-honored theoretical development system of ethnic medicine,unique diagnosis and treatment methods with ethnic characteristics,as well as patent prescriptions that are summarized and developed for various diseases.However,obstacles such as high cost,complicated processing techniques and medication methods,as well as those in cultural exchanges are impeding the development process of Tibetan medicine.In an era where modern medical technologies and traditional Chinese medicine are advancing hand in hand,this paper proposes strategies to promote Tibetan medicine’s industrialization,policy support,social attention,and internationalization,in order to advance the use of Tibetan medicine in serving a greater number of people with its unique benefits,and thus realizing the dream of“Healthy China.”

Textual Research on Name, Variety and Property of the Multi-origin Tibetan Herb "Azhong"

By consulting ancient Tibetan medical literature such as books of materia medica,medical works,and prescription books,as well as modern and contemporary literature and materials,and in combination with the interview and investigation of clinical use and expert consultation,we collated and verified the name,variety classification,plant origin,application and other recorded information of Tibetan herb"Azhong",and summarized and analyzed the phenomenon of mixed use or substitution of medicinal plants.According to textual research,it first appeared in the Four Medical Tantras.The Tibetan herb"Azhong"is simply recorded in the ancient books and Materia Medica,which are collectively called"Azhong".Since the 15 th century,there have been varieties such as Za Azhong,Kan Azhong,Xing Azhong,Pumou Azhong,Zha Azhong,Bang Azhong,and the top grade is called Azhong Nabu and Nacang Azhong,and the bottom grade is Azhong Gabu.According to modern literature,the origin of"Azhong"involves 12 species of plants belonging to 8 genera,5 families.At present,Arenaria kansuensis Maxim,Ajania purpurea Shih.and Thalictrum squamiferum Lecoy are the mainstream medicinal materials of"Azhong".There is a certain basis for clinical application and theoretical records in the literature in terms of the mutual alternative use of Tibetan medicinal materials such as"Azhong"and traditional medicinal materials in different regions.Therefore,it is necessary to use modern chemical technology and pharmacological experiments to conduct a comparative study on the material basis and biological activity of different varieties of medicinal materials,and carry out a survey on resources and use status,so as to standardize the use of their varieties and origins and improve the safety of clinical medication.

Contribution of Tibetan Medicine To Embryology

Tibetan medicine has a history of some 2,000 years. It is a shining pearl in the cultural treasure house of the great motherland. In the prolonged process of combating disease, the Tibetans came to understand the parts of animals and plants, and the mineral ores which have medical effect for certain kinds of pain and suffering. With the deepening of understanding of nature, and with the development of production, they started to study the human body.

Compatibility Rules of Prescriptions of Tibetan Medicinal Material Mirabilis himalaica(Edgew.)Heimerl Based on Data Mining

[Objectives]To study the prescription compatibility rules of the Tibetan medicinal material Mirabilis himalaica(Edgew.)Heimerl(Himalayan purple jasmine)based on data mining,and to provide reference for clinical application and new drug development.[Methods]The literature data were collected and the prescriptions containing Himalayan purple jasmine were sorted and classified by Microsoft Excel 2019 software.The Traditional Chinese Medicine Inheritance Computing System(TCMICS 3.0)was used to statistically analyze the high-frequency drugs and core drug combinations,the frequency of disease treatment,and the rules of"tastes transforming flavors"of drugs.The FP-tree algorithm was used to analyze the association rules among various Tibetan medicinal materials in the prescriptions,and different supports were set to analyze the compatibility rules of the prescriptions.[Results]There were a total of 129 prescriptions containing Himalayan purple jasmine,297 medicinal materials used in combination with it,and 34 Tibetan medicinal materials with a frequency of≥15.The medicinal flavors were mostly sweet,bitter,and pungent.Among the three flavors,bitterness and sweetness were the majority.At the same time,the medicinal properties were blunt,soft,cool,and warm.A total of 130 kinds of diseases were involved,among which 8 kinds of diseases such as gynecology,kidney cold and yellow water disease had a high frequency.Through association rule analysis,33 commonly used core drug combinations were obtained.The support,confidence,and frequency of the five drug combinations[Jili(Tribuli Fructus),Huangjing(Polygonati Rhizoma),Tianmendong(Root of Cochinchinese Asparagus),and Tibetan Aoruqin(Vicatia coniifolia)]→Himalayan purple jasmine were the basic prescription of Tibetan medicine Wudagen Powder.The drug combinations with higher confidence included Bibo(Piperis Longi Fructus)→Himalayan purple jasmine,Pomegranate(Punica granatum→Himalayan purple jasmine,Baidoukou(Round Cardamom Fruit)→Himalayan purple jasmine,Hezi(Chebulae Fructus)→Himalayan purple jasmine.Jili(Tribuli Fructus)→Himalayan purple jasmine,Huangjing(Polygonati Rhizoma)→Himalayan purple jasmine and Tianmendong(Root of Cochinchinese Asparagus)→Himalayan purple jasmine had highest frequency.[Conclusions]Through the TCMICS,this paper analyzed the compatibility rules of commonly used drugs containing Himalayan purple jasmine and the characteristics of the main diseases.It can be seen that Himalayan purple jasmine is sweet in taste and warm in nature.It assists sovereign drugs in the form of ministerial drugs,which enhances the effect of regulating"long"and nourishing,and plays the role of regulating"long",dispelling cold,and reconciling various drugs,which embodies the compatibility rules of sovereign and ministerial drugs of Tibetan medicines.The main diseases of Himalayan purple jasmine are related to"long"regulation,and it is mostly used in the treatment of gynecological diseases after being combined with other drugs to form a prescription.Most drugs in the prescriptions are sweet,which is the therapeutic principle of regulating"long"and nourishing,and verifies the scientific and rational principle of clinical use of Tibetan medicine.In the prescription,the medicinal properties include both warm and cool,and the medicinal taste is sweet and bitter,which is in line with the compatibility theory of"tastes transforming flavors"in traditional Tibetan medicine prescriptions.

History of Tibetan Medicine

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