ABSTRACT
OBJECTIVE：To invest igate the medication regulation of Tibetan medicine prescription of Punica granatum seeds， and to analyze the pharmaceutical property of it in the treatment of “Sanweihuo”（Me drod gusm) dysfunction induced-related diseases. METHODS ：Using Clinical Notes of Tibetan Medicine ，Medicine Standard of the Ministry of Public Health ：Tibetan Medicine as standard ，Tibetan medicine prescriptions of P. granatum seeds recorded in Sibu Yidian ，Yuewang Yaozhen and other medical records were collected ，and TCMISS V 2.5 software was used to analyze main indication and medicine frequency statistically. The core medicine combinations of the prescriptions were analyzed with Apriori algorithm （support degree ≥50％， confidence degree ≥90％)，and medication regulations were analyzed. Tibetan medicine “Ro Nus Zhu rJes ”vector model was used to analyze the properties of Tibetan medicine prescription of P. granatum seeds in the treatment of high frequency diseases ，and K-means cluster analysis was carried out for seventeen effectiveness. RESULTS ：A total of 300 Tibetan medicine prescriptions of P. granatum seeds were collected ，involving 104 kinds of main indications ，among which frequency of 18 kinds of indications was more than or equal to 10 times，including“non-indigestion syndrome ”（Ma Zhu ba) （76 times)，“wood cloth disease ”（Smug po) （46 times)，“edema”（Chu nad) （34 times)，etc. Totally 322 kinds of Tibetan medicines were involved. Among them ，21 flavors were more than or equal to 50 in frequency ，including Piper longum （192 times)，Amomum kravanh （164 times) and Carthamus tinctorius（134 times)，etc. Fifty-six core combinations were obtained ，mainly including P. granatum seeds-P. longum （192 times)， P. granatum seeds-A. kravanh （164 times) and P. granatum seeds-C. tinctorius （134 times). The prescriptions （13 pieces) with six flavors as pungent ，sweet and sour ，and with prominent medicinal properties such as roughness ，heat and dry effects could be used to treat “non-indigestion syndrome ”，and then included into type Ⅰ. The prescriptions （13 pieces) with six flavors as bitter ，sweet and pungent ，and with prominent medicinal properties such as cooling ，dull and heavy effects could be used to treat “wood cloth disease”，and then included into type Ⅱ. The prescriptions （11 pieces) with six flavors as sweet ，sour and pungent ，and with prominent medicinal properties such as dull ，heavy and moistening effects could be used to treat “edema”，and then included into type Ⅲ. CONCLUSIONS ：Tibetan medicine P. granatum seeds is often used in combination with the isothermal medicines such as P. longum ，A. kravanh . P. granatum seeds are also commonly found in cool prescriptions ，revealing that Tibetan medicine pays attention to “Sanweihuo”while treating diseases ，which embodies the academic thought of Tibetan medicine that “there is cooling in temperature ，and there is temperature in cooling ”.
ABSTRACT
OBJECTIVE：To investigate t he p otential mechanism of Tibetan medicine Wuwei shexiang pills in the treatment of “Grum bu ”disease（i.e. rheumatoid arthritis ）. METHODS ：Referring to Sibu Yidian ，Drug Standard of the Ministry of Public Health（Tibetan Medicine ），Jingzhubencao，the constituent ，dose and flavor of Wuwei shexiang pills were collected ；vector structure model was built. From the aspects of six tastes ，three tastes after digestion and seventeen effects ，the properties of the formulation were analyzed ；the“formulation-drug property-disease ”network for the treatment of “Grum bu ”disease was constructed by using Gephi 0.9.2 complex network software. The effective components of Wuwei shexiang pills were screened by using the pharmacology analysis platform of TCM system and the database of organic small molecule biological activity. The target proteins corresponding to the active components were predicted by using BATMAN-TCM network pharmacology research platform ； the target proteins of “Grum bu ”disease were searched by ETCM database. On the basis of screening the common targets of the two，David 6.8 bioinformatics resource database was adopted to conduct gene ontology （GO） analysis and KEGG pathway enrichment analysis ；the network of Wuwei shexiang pills- “Grum bu ”- target-pathway was constructed by using Cytoscape 3.7.0 software，and the network topology analysis was carried out to screen the core targets. Using Glide score as evaluation index ， Maestro Version 11.1.011 software was used for molecular docking of above core targets with effective components of Wuwei shexiang pills. RESULTS & CONCLUSIONS ：Wuwei shexiang pills contains myrobalan ，Aconitum pendulum ，Aucklandia lappa ， Acorus calamus and artificial moschus ，and the highest dosage was myrobalan. The six tastes of this formulation were mainly bitter and sweet ；the three tastes after digestion were mainly bitter ；the seventeen effects were mainly blunt ，cool and heavy ，which were mainly used to treat twenty characteristics such as acute ，hot and light. In “formulation-property-disease”network，higher values of edge weight between seventeen effects and twenty characteristics were cooling effect-heat ， blunt effect-sharpness ， heavy effect-light，dilute effect-odor （edge weight values ≥430），etc. A total of 2 306 potential targets of effective components of Wuwei shexiang pills ，211 targets related to “Grum bu ”disease，32 common targets and 29 corresponding effective components were obtained. The results of GO analysis showed that 52 relative results were predicted ，the common targets mainly located in the extracellular area ，nucleus and other parts ，mainly including biological processes and molecular functions such as immune response，inflammatory response ，cytokine activity. The results of KEGG enrichment were significant in 31 pathways（P＜0.05）， involving TNF signaling pathway ，cancer pathway and other signaling pathways. There were 94 active components ，targets and pathway nodes in the network of Wuwei shexiang pills- “Grum bu ”-target-pathway，and 460 edges；TNF，FAS，IL6，IL10， FASLG，PTGS2 and IL 1B were the core targets of the network ， connected with effective components such as quinic acid ， thymol，dehydroepiandrosterone，norcaxone by Van Der Waals force ，hydrogen bond and hydrophobic interaction ，Pi-cation bond and other bonds ，so as to play a role in the treatment of “Grum bu ”disease.