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ρ-Coumaric acid prevents high fat and high sucrose-mediated hepatic inflammation and fibrosis.

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Abstract
Chronic intake of high fat and high sucrose (HFHS) cause hepatic inflammation and fibrosis. Activation of hepatic stellate cells (HSC), which is the dominant effector during liver fibrosis, is trigged by NLR family pyrin domain containing 3 (NLRP3) inflammasome. p-coumaric acid (4-hydroxycinnamic, PCA) found in edible plants and fruits has been known as a natural bioactive component to have powerful anti-oxidant and anti-inflammatory properties. However, it is not well understood. The impact of PCA on the induced hepatic fibrosis and it’s underlying mechanism. To test this hypothesis, C57BL/6 male mice were randomized into three groups, low fat (LF) diets (11% calories from fat), high-fat diets (60% calories from fat) with high sucrose (20% sucrose, HFHS) drink, or HFHS plus PCA treatment (HFHS+PCA, 50 mg/kg b.w) by intraperitoneal injections. After feeding for 13 weeks, HFHS-fed mice increased body weight and lipid profiles with abnormal glucose metabolism compared to that of the LF diet group. Although HFHS+PCA did not make significant changes in most obesogenic parameters compared to the HFHS group, hypercholesterolemia and insulin resistance marker HOMA-IR were improved by PCA treatment. Interestingly, HFHS-induced hepatotoxicity and hepatic fibrosis which evidenced by endoplasmic reticulum (ER) stress, inflammation gene expression and collagen accumulation were significantly attenuated by PCA. We confirmed the anti-fibrogenic properties of PCA by using LX-2 hepatic stellate cells. NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, which are main contributor of HSC activation, was significantly reduced by PCA in bone-marrow derived macrophages. These findings support the fact that PCA could reduce the HFHS diet-mediated hepatic fibrosis, and it is partly associated with inhibition of inflammasome.
Author(s)
Truong, Thi My Tien
Issued Date
2022
Awarded Date
2022. 2
Type
Dissertation
URI
https://dcoll.jejunu.ac.kr/common/orgView/000000010529
Alternative Author(s)
트롱 티 마이 티엔
Affiliation
제주대학교 대학원
Department
대학원 차세대융복합과학기술협동과정
Advisor
Kang, In Hae
Table Of Contents
List of Figure ii
List of tables iii
Abstract 1
1. Introduction 5
2. Materials and Methods 20
2.1. Experimental chemicals and reagents preparation 20
2.2. Animals and diets 20
2.3. Glucose tolerance test (GTT) and insulin tolerance test (ITT) 21
2.4. Serum biochemistry parameters measurement 21
2.5. Tissue preparation and histological examination 22
2.6. Accumulation of lipids in the liver 23
2.7. Malondiadehyde (MDA) assay 23
2.8. Cell culture and treatment 24
2.9. Analysis of mRNA by Real-time Polymerase Chain Reaction 24
2.10. Protein Isolation and Western Blotting 25
2.11. Statistical Analysis 26
3. Result 27
3.1. PCA supplementation ameliorated HFHS-mediated glucose and insulin tolerance 27
3.3. PCA suppressed HFHS diet-mediated hepatic inflammation, and hepatic stress 31
3.4. PCA supplementation improved HFHS-mediated fibrosis in the liver and LX-2 hepatic stellate cells 34
3.5. PCA inhibited NLPR3 inflammasome activation in macrophages 37
4. Discussion 39
References 43
Supplement Table 52
Degree
Master
Publisher
제주대학교 대학원
Appears in Collections:
Interdisciplinary Programs > Interdisciplinary Graduate Program in Advanced Convergence Technology and Science
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