Clinical Research In The Treatment Of Lower Extremity Lymphedema By Modified Tetrandra And Poria Decoction

Objective:To explore the clinical efficacy and safety of Modified Tetrandra and Poria Decoction in the treatment of lower extremity lymphedema（LEL）with Spleen Dampness by observing the changes of symptoms and signs of patients with LEL（Spleen Dampness）;to explore the mechanism of Tetrandra and Poria Decoction in the treatment of lymphedema by using the network pharmacology and molecular docking technology.Methods:60 patients with LEL（Spleen Dampness）who met the inclusion and exclusion criteria in the Department of Vascular Surgery in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine were randomly divided into observation group（n=30）and control group（n=30）according to the method of random number table.The observation group was treated with Modified Tetrandra and Poria Decoction,and the control group was treated with Diosmin tablet.The treatment period was 14±1 days.The limb circumferences of both lower limbs were measured,LEL index and the differences of limb circumferences of both lower limbs were calculated;doppler ultrasound was used to measure the thickness of the whole layer of skin,subcutaneous tissue and deep fascia of both lower limbs then calculate their thickening,and to observe the morphology and echo of subcutaneous tissue;and Traditional Chinese Medicine（TCM）syndrome score,safety index and adverse reactions were also evaluated before and after treatment.Traditional Chinese Medicine System Pharmacology Database and Analysis Platform was used to retrieve the active ingredients and related targets of Tetrandra and Poria Decoction,which was one of the classical prescriptions of TCM,and target standardization was carried out through Universal protein Database;the lymphedema targets were retrieved from Gene Cards database,and the targets of Tetrandra and Poria Decoction and lymphedema were introduced into the Venn map website to obtain the common targets;String online database was used to construct Protein-Protein Interaction（PPI）network;Cytoscape software was used to construct the active ingredient of Tetrandra and Poria Decoction-active ingredient-target network;Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment analysis of potential targets were carried out by using Metascape online database;finally,molecular docking between key active components and core targets was carried out through Swiss Dock online platform.Results:（1）After treatment,the limb circumference difference,LEL index,whole skin thickness,subcutaneous tissue thickness,deep fascia thickness,and TCM syndrome score of the observation group were effectively improved（P<0.05）.（2）After treatment,the TCM syndrome score of the observation group was significantly better than that of the control group（P<0.01）.（3）The total effective rate of the two groups was 100%,and the markedly effective rate（76.67%）was significantly better than that of the control group（26.67%）and the difference was statistically significant（P<0.01）.（4）During the treatment period,there were no obvious abnormalities in safety indexes and no adverse reactions in the two groups.（5）129 active components and 144 targets were selected from Tetrandra and Poria Decoction,including quercetin,kaempferol,β-sitosterol and so on;38 common targets between lymphedema and Tetrandra and Poria Decoction were obtained by Venn map;31 acting nodes were selected by PPI network,and the core targets included MAPK1,JUN,TP53 and so on;12 KEGG enrichment pathways were obtained,the main pathways included Pathways in cancer（hsa05200）,AGE-RAGE signaling pathway in diabetic complications（ko04933）,MAPK signaling pathway（hsa04010）and so on.（6）The binding energies between key active components such as quercetin and core targets such as MAPK1 are less than-5.0 kcal·mol^-1.Conclusion:Modified Tetrandra and Poria Decoction in the treatment of LEL（Spleen Dampness）can obviously relieve the symptoms of lower extremity swelling,tension and pain,reduce the thickness of whole skin,subcutaneous tissue and deep fascia,and is clinically safe and effective.Its effect is the result of the interaction among multi-components,multi-targets and multi-pathways of Tetrandra and Poria Decoction.There is a good binding activity between the key components and core targets,and the main action mechanism may be related to the action of quercetin on MAPK1 targets to regulate the expression of MAPK signaling pathway,which provides a new train of thought and theoretical basis for the treatment of LEL in the future.