Study On The TCM Medication Rules, Network Pharmacology And Clinical Efficacy Of Dry Eye Caused By Meibomian Gland Dysfunctio

Objective:This study aims to summarize the principles and techniques of traditional Chinese medicine(TCM)for treating meibomian gland dysfunction(MGD)-related dry eye disease(DED)by data mining.Additionally,the aim is to investigate the signal pathway and mechanism of core drug pairs used in TCM’s internal and external treatments for MGD dry eye through network pharmacology and molecular docking technology,respectively.This will enable the creation of new prescriptions that can serve as a reference for clinical and follow-up research.Finally,a clinical trial was conducted to observe the actual efficacy of Jia Wei Xiao Yao Wan in treating MGD dry eyes with liver stagnation and spleen deficiency syndrome and verify the conclusions drawn from the previous theoretical investigations.Methods:Part one:In the data mining section,we searched for clinical efficacy observation literature on traditional Chinese medicine(TCM)treatment of MGD dry eye on the China Knowledge Network(CNKI),Wanfang Data Knowledge Service Platform(WANFANGDATA),and Chinese Journal Service Platform(VIP).Prescriptions that met standard documents were extracted and inputted into Microsoft Excel 2021 to establish a prescription database.After standardization,we counted the frequency and characteristics of drigs.IBM SPSS series statistical software was used for association rule analysis and clustering analysis,and Cytoscape 3.7.2 was used for visual processing.Part two:In the network pharmacology section,we used online bioinformatics analysis tools(TCSMP and BATMAN-TCM)to collect the active components of core drugs and their corresponding targets.We then combined this with disease target databases(DrugBank,OMIM,GeneCards,TTD)to query disease potential targets and obtain drug-disease intersection target genes.We analyzed the intersection target and the active components of traditional Chinese medicine using Cytoscape 3.7.2 software and drew the complex network of "drug-active component-target." We also constructed a protein interaction network using String software.We performed GO functional enrichment analysis and KEGG signal pathway enrichment analysis on common target genes using the DAVID data analysis platform.Finally,we docked the drug active components and key targets with AutoDockVina(1.1.2)to verify their interaction activity.Part three:In the clinical trial section,we collected 31 outpatients diagnosed with MGD dry eye with liver stagnation and spleen deficiency syndrome from the Department of Ophthalmology at Dongfang Hospital of Beijing University of Traditional Chinese Medicine from June 1,2022 to March 31,2023.The control group was treated with sodium hyaluronate eye drops and diclofenac sodium eye drops for external use,while the observation group received Jiawei Xiaoyao Wan orally in addition to the control group treatment for 30 days.We measured related observation and curative effect indexes before and after treatment to evaluate the efficacy of Jiawei Xiaoyao Wan and eye drops in the treatment of MGD dry eye with liver stagnation and spleen deficiency syndrome and compared the difference between the two groups.Results:Data mining part(1)38 prescriptions of traditional Chinese medicine(TCM)for internal use in treating MGD dry eye were analyzed.A total of 104 TCM ingredients were found in the prescriptions,with a cumulative frequency of 378.The top 10 most frequently used TCM ingredients were chrysanthemum,Poria,Ophiopogon,Chinese wolfberry,moutan,Radix scrophulariae,Radix Rehmanniae,licorice,Angelica sinensis,and yam.The main therapeutic effects of these ingredients were to tonify deficiency and clear heat.The medicinal properties were mainly cold,warm,and flat,and the flavors were mainly sweet,bitter,and pungent.These ingredients were attributed to the three meridians of lung,liver,and kidney.Seven groups of drug combinations with the closest correlation were identified by association rules.High-frequency drugs were roughly divided into eight categories by cluster analysis.(2)56 prescriptions of TCM for external use in treating MGD dry eye were analyzed.A total of 93 TCM ingredients were found in the prescriptions,with a cumulative frequency of 466.The top 10 most frequently used TCM ingredients were chrysanthemum,honeysuckle,mint,Ophiopogon,dandelion,Radix Rehmanniae,Forsythia,Radix scrophulariae,Scutellaria baicalensis,and Chinese wolfberry.The main therapeutic effects of these ingredients were heat-clearing,supplemented by drugs for relieving appearance and tonifying deficiency.The most common medicinal property was cold,followed by warm.The flavors of these ingredients were mainly bitter,sweet,and pungent.They were mainly attributed to the three meridians of liver,lung,and stomach.Five groups of drug combinations with the closest correlation were identified by association rules.Highfrequency drugs were roughly divided into eight categories by cluster analysis.Network pharmacology part(1)Fifty active compounds from chrysanthemum and wolfberry were identified from the TCMSP database,corresponding to 200 potential targets.There were 52 overlapping targets between the drug’s active components and MGD dry eye disease.The target protein interaction network diagram indicated that chrysanthemum and Lycium barbarum’s active components mainly exerted their biological effects by acting on AKT1,IL6,TNF,TP53,VEGFA,IL1B,EGF,PTGS2,and other targets.The results of the enrichment analysis of GO function and KEGG pathway showed that there were 344 potential GO functions and 99 signal pathways involved in the treatment of MGD dry eye.(2)A total of 63 active components were identified through the TCMSP and BATMAN-TCM databases,corresponding to 905 potential targets,resulting in 122 target genes for interaction between meibomian gland dysfunction dry eye and drug active components.The target protein interaction network map showed that the active components of traditional Chinese medicine mainly acted on AKT1,TP53,TNF,EGFR,IL6,VEGFA,IL1B,INS,EGF,CXCL8,and other targets to exert biological effects.The results of the enrichment analysis of GO function and KEGG pathway showed that there were 530 potential GO functions and 107 signal pathways involved in the treatment of MGD dry eye with external use of traditional Chinese medicine.Clinical trial partBoth groups showed improvement in the scores of the ocular surface disease index scale(OSDI)and the quantitative scores of TCM syndrome of dry eyes with meibomian gland dysfunction of liver depression and spleen deficiency(P<0.05).However,the treatment group showed greater improvement in TCM disease and syndrome scores compared to the control group(P<0.05).According to the curative effect index of TCM disease score,the treatment group was significantly effective in 6 cases,effective in 9 cases,ineffective in 0 cases,the total effective rate was 100%;the control group was markedly effective in 0 case,effective in 10 cases,ineffective in 6 cases,the total effective rate was 62.5%.Conclusions:Data mining part(1)The internal prescription for treating MGD dry eye reflects the therapeutic principles of tonifying the liver and kidney,nourishing yin and clearing heat,dispersing wind-heat,clearing heat and dampness,and activating blood circulation and dredging collaterals.Among these principles,the emphasis is on tonifying the liver and kidney,tonifying essence,and improving vision.Most of the drugs used are sweet-cold tonics for deficiency and heat-clearing,while warm-flat tonics for deficiency are also common.The drugs mainly affect the lung,liver,and kidney meridians.Comprehensive analysis reveals that the core drug combination is Qiju Dihuang decoction,and the high-frequency core drug pair is chrysanthemum-wolfberry.(2)The external prescription for treating MGD dry eye also reflects the therapeutic principles of nourishing yin and clearing heat,clearing heat and dampness,dispersing wind-heat,and promoting qi,promoting blood circulation,and dredging collaterals.The main drugs used are bitter-cold herbs for clearing heat,dryness,and dampness,as well as sweet-cold herbs for nourishing yin and clearing heat,and pungent herbs for dispelling wind,promoting qi,and activating blood.The main meridians affected are the liver,lung,and stomach meridians.Comprehensive analysis reveals that the core drug combinations are chrysanthemum,Radix Rehmanniae,Ophiopogon,Forsythia,Radix scrophulariae,and Flos Lonicerae.Network pharmacology part(1)The most closely related signaling pathways to the treatment of dry eye with meibomian gland dysfunction through oral prescription of traditional Chinese medicine are the MAPK signal pathway,PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,TNF signal pathway,and Calcium signaling pathway.These pathways suggest that the potential mechanism of oral prescription drugs in treating this disease may involve inhibition of apoptosis,anti-inflammation,anti-late glycosylation,and promotion of corneal epithelial repair.(2)The most closely related signaling pathways to the treatment of dry eye with meibomian gland dysfunction in the core drug group of traditional Chinese medicine are the MAPK signal pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,Calcium signaling pathway,and Cytokine-cytokine receptor interaction.It suggests that the potential mechanism of external prescription of traditional Chinese medicine may involve antiinflammation and repairing the corneal epithelial barrier to treat dry eye with meibomian gland dysfunction.Clinical trial partBoth groups were effective in relieving dry eye symptoms and systemic symptoms.The improvement degree of TCM syndrome score in the treatment group was better than that in the control group treated with western medicine eye drops alone.Jiawei Xiaoyao Wan and eye drops has a good effect on treating MGD dry eye with liver stagnation and spleen deficiency syndrome.