Safety Study Of Mongolian Medicine Tiexie Wuwei Decoction Based On Retrospective Analysis Of Literature And Clinical Applicatio

Objective:Tiexie Wuwei Decoction(Temuren Talaha-5 Decoction)is a classic preparation commonly used in Mongolian medicine,whose safety has been questioned due to the presence of heavy metals.Therefore,this study summarized and discussed the safety of this decoction through ancient and modern literature research,network toxicology research and retrospective analysis of clinical application,so as to provide theoretical and data support for clinical safety application and basis for safety evaluation research.Methods:(1)The manual literature retrieval method was adopted to search and sort out the relevant provisions of Tiexie Wuwei Decoction in the ancient literature database of Mongolian medicine(http://39.104.204.66:8083/)and modern literature of Mongolian medicine.Philology research method and textual research method were used to analyze the historical origin,drug composition,main symptoms,principles of formulating prescription,drug dose,usage and dosage,toxicity records,etc.(2)Through TCMSP database,PubMed database,CTD database and related literature reports to screen the toxic components of Tiexie Wuwei Decoction.Toxic component protein targets were screened by Swiss Target Prediction.Drugbank and ChemMapper databases,and the key toxic component targets were obtained by the interaction analysis of toxic component target proteins using STRING database.DAVID database was used for GO bioenrichment analysis and KEGG pathway enrichment analysis of toxic component targets to predict the toxic mechanism.(3)According to the previous literature study and the results of network toxicology study,the clinical application retrospective analysis method was adopted to further observe the clinical application and safety of Tiexie Wuwei Decoction.Collecting the electronic medical records of patience from January 2017 to December 2021 who treated with Tiexie Wuwei Decoction at the outpatient department of Inner Mongolia international medical hospital,Xing’an League Mongolian Medical Hospital,Kulunqi League Mongolian Medical Hospital and the inpatient department of Inner Mongolia University for Nationalities,Affiliated Hospital of Inner Mongolia Minzu University.Xing’an League Mongolian Medical Hospital.Basic information,diagnosis information,medication information and related indicators of liver and kidney function before and after medication were extracted,and the relevant data were input into Microsoft Excel 2019 according to unified standards,and the database of Clinical Retrospective Analysis of Tiexie Wuwei Decoction was established.Descriptive analysis and association rule analy sis of relevant data were conducted by Microsoft Excel 2019 and IBM SPSS Modeler 18.0.Results:(1)The results of literature research:Tiexie Wuwei Decoction is included in 17 Mongolian medical literature.According to the results of literature examination,the earliest w ritten record of Tiexie Wuwei Decoction found in Puji miscellaneous prescription(1872 editi on)or Gao shige handwritten prescription book whose author is Gao Shige.In addition to Tie xie Wuwei Decoction,there are 9 other different names.The composition of the drugs in the f ormula and the base source of the drugs are stable,and the dosage ratios in modern literature a re basically the same as those recorded in ancient literature.With the accumulation of clinical practice,the main therapeutic effects of Tiexie Wuwei Decoction are enriched continuously.T he main effects are clearing heat,cooling blood and brightening eyes,mainly treating liver-he at and blood-heat type of eye diseases,which is a formula with harmonized sexual taste,diges tive taste and efficacy.The general preparation of this formula is to crush the five herbs into fi ne powder or coarse powder,and the dosage form is mostly in soup,decoction with water,3-5 g per oral dose,or it can be used externally to fumigate the eyes.It was recorded in Inner Mo ngolia Standard of Mongolian Medicine,Chinese Medical Encyclopedia·Mongolian Medicin e and Chinese Materia Medica · Mongolian Medicine Volume that fructus toosendan was mild ly toxic,while other drugs were non-toxic.No toxicity record and adverse reactions were repo rted about the whole formula.The results of literature review show that short-term or long-ter m oral administration of iron-containing preparations can cause gastrointestinal irritation sym ptoms,and even lead to iron overload leading to organ and tissue damage.Excessive use of fr uctus gardenia and Neem seed has hepatorenal toxicity.(2)The research methods of network t oxicology:40 potential toxic compounds and 687 related toxic compound target proteins were predicted for Tiexie Wuwei Decoction.The toxic components in Tiexie Wuwei Decoction ma inly act on SRC,HSP90AA1,MAPK1,MAPK3,HRAS,PIK3R1,PIK3CA,STAT3,AKT1,L YN and other key targets,and participate in protein phosphorylation,cell apoptosis,and intrac ellular signal transduction regulation.Mainly through PI3K-Akt signaling pathway,chemokin e signaling pathway,Ras signaling pathway,T cell receptor signaling pathway,neurotrophic si gnaling pathway can cause hepatotoxicity,renal toxicity,cardiotoxicity,neuroimmune system damage,etc.(3)Clinical application of retrospective analysis results:A total of 950 cases wer e collected.According to the exclusion criteria,16 cases were excluded,and finally 934 cases were included,including 741 outpatients and 193 inpatients.The users were mainly young an d middle-aged patients aged 18-60 years.The clinical departments are mainly ophthalmology,often used for conjunctivitis,uveitis,belongs to Mongolian medicine cold red eye,red eye dis ease,as well as cerebral infarction,diabetes,chronic hepatitis,hyperthyroidism and other dise ases that can lead to eye lesions.The main treatment symptoms are vision loss,red eye,eye p ain.The dose of single dose is mainly 3 g,the number of days of medication is mostly within one week,and the medication is mainly taken by water decoction and can be used externally t o fumigate the eyes with steam.Zhenbao pills and Honghua Shisan powder are the main com bination of Mongolian medicines.Levofloxacin eye drops or praprofen eye drops are the most commonly used in combination with Western medicine.No abnormal changes of liver functio n and renal function were observed in clinical cases.Conclusion:No toxicity was found in the ancient and modern literature of Tiexie Wuwei Decoction.Although the network toxicology analysis predicted the possibility of liver and kidney injury caused by the application of this formula,the retrospective analysis of clinical cases has not found adverse reactions of liver and kidney function injury in the conventional dosage users.Therefore,it is necessary to scientifically evaluate the safety of Tiexie Wuwei Decoction through further basic experiments and clinical observation.