Title Page

Contents

Abstract in English 8

Ⅰ. Introduction 10

Ⅱ. Method 13

Human data 13

Binge preparation 13

MASLD animal Model 14

Liver histological analysis 14

Quant-Seq Microarray 15

Stool analysis for 16S rRNA amplicon sequencing 16

Western blot analysis 17

Realtime-quantitative Polymerase Chain Reaction 18

Ⅲ. Results 20

1. Gut microbiota in patients with metabolic associated-steatotic liver disease. 20

2. Administration of combination of myricetin and compound K alleviates hepatic injury in MASLD. 22

3. Administration of a combination of Myrcetin and Compound K improves Hepatic metabolism. 26

4. Administraion opf a combination of Myricetin and Comp ound K moudulates Wnt signaling pathway. 30

5. Changes in taxonomic structure of gut microbiota during combination administration. 32

6. Administration of myricetin and compound K alleviates hepatic injury in MASLD. 36

7. Administration of Myrcetin and Compound K improves hepatic metabolism and Wnt signalingpathway control ability. 39

8. Myricetin and compound K administration results in cha nges in the taxonomic structure of gut microbiota. 43

9. RNA-seq reveals the potential roles of Myricetin and Compound K in the liver of MASLD mice. 47

Ⅳ. Discussion 51

Ⅴ. Reference 59

Abstract in Korean 65

Table 1. List of primer performed qPCR. 19

Table 2. Baseline characteristic of the participants. 21

Figure1. Network pharmacology analysis and human data. 21

Figure2. Effects of hepatic pathology and liver function after administration of Myricetin, Compound K mixture in MASLD model. 23

Figure3. NALFD activity score and Blood Biochemical Analysis. 25

Figure4. The administration of a mixture of Myricetin, compound K regulates liver lipids and inflammation. 28

Figure5. The administration of a mixture of myricetin, Compound K can regulate genes in Wnt signaling in the liver. 31

Figure6. Gut Microbiota change in myricetin and Compound K mixtures supplementation. 34

Figure7. Effects of hepatic pathology and liver function after administration of Myricetin and Compound K in MASLD model. 37

Figure8. The administration of myricetin, Compound K can regulates liver lipids and inflammation and Wnt target gene. 41

Figure9. Gut microbiotas change in supplementation of myricetin and Compound K 45

Figure10. RNA microarray Analysis of New Genetic Changes in the Liver. 49