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.

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.

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.

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.

<i>Ratanasampil</i>(Tibetan Medicine, RNSP) Reduces <i>β</i>-Amyloid Protein (Aβ) and Pro-Inflammatory Factor Levels and Improves Cognitive Functions in Mild-to-Moderate Alzheimer’s Disease (AD) Patients Living at High Altitude

Ratanasampil (RNSP) is a traditional Tibetan medicine used for the treatment of stroke and cerebrovascular diseases. Previous discoveries that RNSP can reduce β-amyloid protein levels and increase learning and memory in Alzheimer’s mouse models (Tg2576) led us to investigate whether RNSP can improve cognitive functions in Alzheimer’s patients. In this study, 146 AD patients living in Qinghai province received either one gram or 0.33 gram daily of RNSP for 16 weeks. Placebo patients received Piracetam. Serum Aβ40 and Aβ42 levels were measured at the beginning of the study and after 4 and 16 weeks of treatment. Compared to the same group before treatment, MMSE scores, ADAS-cog scores and ADL scores were significantly improved (p 0.05, p > 0.05). After 16-week treatment, serum TNF-α, IL-1β, IL-6 and Aβ42 levels were significantly decreased (p < 0. 01) in the high-dose RNSP group, whereas no significant differences were found in the low-dose and placebo groups. The Aβ42/Aβ40 ratio was significantly decreased after 4-week and 16-week treatment in the high-dose RNSP group (p < 0. 05, p < 0.01). Furthermore, serum Aβ42 concentrations had a strong positive correlation with TNF-α, IL-1β and IL-6 levels. There were no observable adverse effects in either treatment or control groups. We conclude that further clinical trials of RNSP in Alzheimer disease are warranted.

Anti-inflammatory effect of plant compositions of Tibetan medicine in vitro on early rheumatoid arthritis

Materials and Methods: lymphocytes of 10 pa-tients having early rheumatoid arthritis (RA) (the duration of the illness was 3 - 6 months) with a marked exudational process in joints were ex-amined. The content of lymphocytes expressing the CD3, CD4, CD8, CD16, CD56, CD20, CD72, CD38, CD23, CD25, CD71, HLA-DR, CD95, CD30, CD54, mIgM, mIgG antigens was determined. Results: the “Taban-Arshan” extract corrects the changes of the immune system characterized by the evident activation of the B-cell part of the immune system and normalizes immune parameters of the lymphocytes taken from the patients with autoimmune diseases (early rheumatoid arthritis). The immunocorrective effect of the “Taban-Arshan” extract is related to its ability to suppress the lymphocyte increased activation by normalizing expression of the main activation antigens (CD23, CD25, CD71, HLA-DR, CD54).

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.

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.

Correlation between Tibetan and traditional Chinese medicine body constitutions: A cross-sectional study of Tibetan college students in the Tibet Autonomous Region

Objective:To evaluate the correlation between the body constitution types of Tibetan medicine and traditional Chinese medicine (TCM).Methods:The cluster sampling method was employed to recruit participants from a university in the Tibet Autonomous Region.Tibetan medicine and TCM questionnaires were respectively used to assess the participants' constitution information.Descriptive statistics were applied to analyze the baseline and constitution characteristics of the participants.Two-factor correlation analysis and the paired chi-square test were applied to analyze the correlation between Tibetan and TCM constitution types.Results:Data from 466 Tibetan students were analyzed.The mean scores of the rlung,mkhris pa,and bad kan constitution types in Tibetan medicine were 43.2 (11.1),42.1 (10.1),and 45.0 (8.0),respectively;participants with the three-factor convergence body constitution type accounted for 13.7% of the whole population.Among the TCM constitution types,qi stagnation was the most common (21.5%),followed by the balance type (16.5%);the other constitutions detected were qi deficiency,yin deficiency,and yang deficiency.The rate of consistency for the identification of the three-factor convergence constitution in Tibetan medicine and the balance constitution in TCM was 89.1%,with a Kappa coefficient of 0.57 (P >.05).The rlung constitution in Tibetan medicine was associated with the yin deficiency,yang deficiency,and blood stasis constitutions in TCM.The mkhhris pa constitution in Tibetan medicine was associated with the damp heat and yin deficiency constitutions in TCM.The bad kan constitution in Tibetan medicine was associated with the phlegm dampness,qi deficiency,and yin deficiency constitutions in TCM.Conclusion:There is a correlation between the body constitution types of Tibetan medicine and TCM.The reliability and validity of the Questionnaire for TibetanMedicine Constitution requires improvement,and more studies with larger sample sizes and more varied populations are warranted to verify the correlation between Tibetan medicine and TCM constitutions.

Preparation and Pharmacodynamic Evaluation of Kang Zhu Gan Lu Oral Proliposome, a New Hypoglycemic Tibetan Medicine

[Objectives]To effectively solve the problem of poor oral bioavailability of total flavonoids in Kang Zhu Gan Lu(ZYZH),a new hypoglycemic Tibetan solid preparation,ZYZH oral proliposome was prepared by modern preparation method,and its hypoglycemic effect was evaluated.[Methods]ZYZH proliposome was prepared by carrier deposition method,and its particle morphology and Zeta potential were detected.Taking encapsulation efficacy as indictor,the optimal prescription and preparation process of ZYZH oral proliposome were screened by orthogonal experiment.In addition,the hypoglycemic activity of ZYZH oral liposome in alloxan-induced hyperglycemic mice was studied.[Results]The repose angle,average particle size,encapsulation efficiency,and Zeta potential of ZYZH proliposome are 34.2°,(442.5±3.5)nm,67.7%and(-47.2±3.4)mV,respectively.Compared with the model group,the fasting blood glucose level of the hyperglycemic mice significantly declined(P<0.01),and their body weight changed insignificantly after four weeks of oral administration of ZYZH proliposome(P>0.05).[Conclusions]The preparation process of ZYZH oral proliposome is characterized by simple operation,high encapsulation efficiency and good stability.The new hypoglycemic Tibetan drug ZYZH oral liposome has obvious hypoglycemic effect on alloxan-induced hyperglycemic mice.

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.

Comparative Study on Tissue Distribution of Tibetan Medicines Renqing Mangjue Compatible with Zuota

[Objectives]To explore the mechanism for the attenuate-synergistic effect of Zuota to Renqing Mangjue,a contrasted study on the tissue distribution of Tibetan medicines Renqing Mangjue compatible with Zuota was carried out. [Methods] The SD rats gastric ulcer model were made successfully,and then respectively were given Renqing Mangjue compatible with Zuota or not according to the dose of 0. 144 g/kg and normal saline by gavage administration,once a day. After 14 d of administration,various organs and tissue were isolated,including brain,heart,liver,spleen,lung,kidney,jejunum,skeletal muscle,fat,skin,submandibular gland,uterus and ovary( or testicle and epididymis).The LC-MS/MS methods were used for determining the contents of brucine and strychnine in various organs and tissue,and significant difference analysis,main target site analysis and clustering analysis were implemented. [Results]Between the Zuota group and non-Zuota group,there was extremely significant difference in the content of brucine in the liver,kidney,muscle,lung,ovary,and heart( P < 0. 01),significant difference in the jejunum( P < 0. 05),and no significant difference in the epididymis,testis,brain,skin and uterus( P > 0. 05); the content of brucine in the submandibular gland,spleen,liver and ovary increased significantly,but significantly reduced in the kidney,muscle,jejunum,lung and heart. And there was extremely significant difference in the content of strychnine in the liver,kidney,ovary,brain and heart( P < 0. 01),and no significant difference in the uterus( P > 0. 05); the strychnine content increased significantly in the liver,spleen and ovary,and significantly decreased in the kidney,muscle,testis,lung,brain and heart.[Conclusions] Compatibility of Zuota can affect the distribution of brucine and strychnine in some tissue and organs,so as to achieve attenuate-synergistic effect of Zuota to Renqing Mangjue.

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.”

Health Preservation Methods Of Tibetan Medicine

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Tibetan Medicine Research

Authored by Huang Fukai, the book constitutes one of the Tibetan Medicine Research Series Books.

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.