Protective Effect of Polyphenols on Non-alcoholic Fatty Liver Disease

Xueyang Tang

, Chen Zhao

, Kunlun Li

, Baojun Li

, Le Su

1,* e

and Lin Zhao

1,* f

State Key Laboratory of Biobased Material and Green Papermaking, Shandong Provincial Key Laboratory of Microbial

Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China

Jinan Hangchen Biotechnology Co., Ltd., Jinan 250353, China

Shandong Food Ferment Industry Research & Design Institute, Qilu University of Technology,

Shandong Academy of Sciences, Jinan 250353, P.R. China

Shandong Zhuoran Biotechnology Co. LTD, China

Corresponding authors

Keywords: Natural Polyphenols, NAFLD, Antioxidant, Anti-Inflammatory.

Abstract: The incidence rate of non-alcoholic fatty disease (NAFLD) has increased in recent years due to poor dietary

habits and lifestyle. However, there is no effective ways for the treatment of NAFLD. Therefore, looking for

therapeutic agents for NAFLD has become a research hotspot. Polyphenols have attracted increasing attention

for the treatment of NAFLD due to its excellent antioxidant and anti-inflammatory properties. They have been

proved to exhibit the therapeutic potential for NAFLD. In this study, we aim to present an overview of the

effect of polyphenols in the treatment of NAFLD.

1 INTRODUCTION

Nonalcoholic fatty liver disease (NAFLD) is the main

cause of liver disease. It is closely related to a group

of metabolic syndrome such as obesity,

hyperlipidemia and insulin resistance (IR). It is a

clinicopathological syndrome characterized by

steatosis and fat accumulation of hepatic

parenchymal cells. NAFLD is caused by excessive fat

accumulation in the liver, especially triglycerides

(TG) (Gaggini 2013, Labrecque 2014). The main

cause of excessive liver fat is central obesity, which

is closely related to insulin resistance (Gaggini 2013)

NAFLD is the most common in liver diseases, with

up to 27% of patients with fatty liver in China, and

the age of onset is becoming younger and younger. In

the past two decades, its prevalence has increased

year by year and even doubled (Gaggini 2013,

Labrecque 2014, Della Corte 2014, Karim 2015). The

role of inflammatory cytokines, mitochondrial

dysfunction and the damage of reactive oxygen free

radicals can further worsen it (Labrecque 2014,

https://orcid.org/0000-0002-7020-7395

https://orcid.org/0000-0003-0042-2193

https://orcid.org/0000-0002-7994-878X

Byrne 2015). NAFLD, as a multisystem disease, may

affect other organs and regulatory pathways, while

increasing the risk of several other chronic diseases,

such as type 2 diabetes, heart disease and chronic

kidney disease (Gaggini 2013, Byrne 2015).

Polyphenols are a kind of natural metabolites

produced by plants, which have a variety of

protective effects on liver diseases and related

diseases. After ingestion of polyphenols, polyphenols

and their metabolites in human body can regulate

lipid metabolism, improve oxidative stress, slow

down the development of inflammatory response and

insulin resistance, reduce liver fat content and

enhance the expression of antioxidant enzymes

through circulation (Al-Dashti 2018, Li 2014,

Nguyen 2017). Therefore, our aim was to outline the

role of polyphenols in the treatment of NAFLD.

Moreover, compared with self-discipline methods

such as improving eating habits, adjusting lifestyle

and strengthening exercise, drinking more

polyphenols has become a more attractive, simple

and easy method to improve nonalcoholic liver

injury.

https://orcid.org/0000-0001-5929-9623

https://orcid.org/0000-0001-7723-5252

https://orcid.org/0000-0002-4329-2723

Tang, X., Zhao, C., Li, K., Li, B., Su, L. and Zhao, L.

Protective Effect of Polyphenols on Non-alcoholic Fatty Liver Disease.

DOI: 10.5220/0011196700003444

In Proceedings of the 2nd Conference on Artiﬁcial Intelligence and Healthcare (CAIH 2021), pages 123-127

ISBN: 978-989-758-594-4

123

2 PROTECTIVE EFFECT OF

NATURAL POLYPHENOLS ON

NAFLD

2.1 Flavonoids

Silymarin is one of the most effective and common

herbs in the treatment of NAFLD (Abenavoli 2010).

Silymarin, a common flavonoid extracted from

silymarin fruit, is the most important component with

the largest content of silymarin. Silybin has shown

biological effect on the protection of liver disease.

Because silymarin has the characteristics of potential

antioxidant, anti-inflammatory and anti fibrosis, it

has been widely used in clinic as the main component

of liver protection drugs (Abenavoli 2010, Federico

2017).

A mouse experiment has proved that silibinin can

improve nonalcoholic liver injury caused by high-fat

diet. The NAFLD model of C57BL / 6J mice was

successfully established through 8 weeks of high-fat

diet. Silibinin (50 or 100 mg / kg / day) was

administered by gavage in the last 4 weeks. Through

the biochemical indexes of blood and liver

homogenate and the metabolomic analysis of serum

and liver samples, silibinin reduced the accumulation

of liver lipids and improved lipid metabolism, It

protects mice from metabolic abnormalities and

nonalcoholic liver injury caused by high-fat diet(Sun

2019). The protective effect of silibinin on the liver

was also confirmed in a clinical trial, which tested

180 patients with NAFLD, analyzed the data of

patients, and proved that the administration of

silibinin vitamin E phospholipid complex (188 mg

silibinin / day) for 12 months can reduce the level of

serum aminotransferase and improve the degree of

hepatic steatosis (Loguercio 2012).

Tea is a traditional beverage in China. Now it is

also accepted and loved by many countries in the

world. The flavonoids in tea have been proved to have

a variety of biological activities. Catechin is one of

the most important components in flavonoid species

and has strong antioxidant activity (Masterjohn

2012). At the same time, the metabolites of catechin

in the body also show antioxidant, anti-inflammatory

and antioxidant stress effects (Feng 2006, Zhou

2014).

In the clinical trial of NAFLD patients, patients

were divided into control, high-density catechin and

low-density catechin groups. They took

corresponding capsules every day for 12 weeks to

maintain a healthy lifestyle. After 12 weeks, serum

index examination showed that high-density catechin

could reduce the level of serum liver enzyme alt,

urinary 8-Isoprostaglandin excretion and body fat.

Experiments have proved that the intake of at least 1g

catechin per day can reduce the liver fat content and

inflammation in patients with NAFLD by reducing

the level of oxidative stress (Sakata 2006).

2.2 Curcumins

Curcumin is a bioactive component extracted from

the rhizomes of Zingiberaceae and Araceae plants.

The content of turmeric is about 3% - 6%, which is a

diketone compound and is used as food flavor and

pigment (Ganjali 2017). Natural polyphenols in

curcumin have become natural compounds for the

treatment of NAFLD because of their lipid

modification, antioxidant, anti-inflammatory, insulin

sensitivity, anti stearation and anti fibrosis properties

(Zabihi 2016).

Some animal experiments also provide evidence

that curcumin has become an effective drug for the

treatment of NAFLD. Intragastric administration of

curcumin can reduce the transaminase activity in

serum, regulate lipid metabolism, and reduce the

proinflammatory and oxidant effects of mouse liver

macrophages (Inzaugarat 2017). Another mouse

experiment proved that curcumin intervention can

significantly reduce liver steatosis induced by high-

fat diet, reverse the abnormalities of serum

biochemical indexes, and control lipid synthesis by

controlling the expression of CD36, SREBP-1c and

Fas (Yan 2018). In addition, in a clinical randomized

controlled trial, 102 patients with NAFLD were

randomly divided into two groups and received 1000

mg curcumin (intervention group) or lactose placebo

(control group) twice a day for 8 weeks. The results

showed that curcumin intervention treatment could

significantly reduce serum total cholesterol, alt, AST,

liver enzyme activity and other biochemical indexes,

and reduce body mass index and waist circumference.

In addition, liver lipid content was reduced in 75% of

patients in the intervention group (Panahi 2016,

Panahi 2017).

2.3 Stilbenes

Resveratrol (RSV) is the most representative

substance of stilbene polyphenols. It is a natural plant

polyphenol with two phenolic rings found in red wine

and various foods such as grapes, blueberries, peanuts

and berries. It mainly has biological activities such as

anti-inflammatory, anti proliferative and antioxidant

(Brown 2010, Charytoniuk 2016).

CAIH 2021 - Conference on Artiﬁcial Intelligence and Healthcare

124

Resveratrol can improve the disorder of lipid

metabolism induced by high-fat diet and prevent the

pro-inflammatory response of liver, such as reducing

TNF in liver- α, IL-6 and NF- κ B mRNA expression

reduces liver adipogenesis markers, such as

triglyceride, body fat, total cholesterol, transaminase

and plasma insulin levels. These effects are related to

the up regulation of SIRT1(Andrade 2013). In

addition, the clinical trial also proved the positive

effect of resveratrol on NAFLD. In the clinical trial

participated by NAFLD patients, the patients took

500g resveratrol capsule every day for three

consecutive months, and the control group took

placebo capsule, and both groups maintained a

healthy diet. After three months, the examination

showed that resveratrol supplementation could

reduce alt, AST enzyme activity, inflammatory

cytokines and nuclear factors in serum κ B activity

and improve lipid accumulation in the liver

(Faghihzadeh 2014, Faghihzadeh 2015).

2.4 Phenolic Acids

Ellagic acid (EA) is one of the most representative

natural phenolic acids. It widely exists in various

plant tissues, such as nuts, soft fruits, etc.

pomegranates, berries and other fruits also contain a

large amount of ellagic acid (Kang 2016). Ellagic

acid has strong antioxidant functions, such as

scavenging oxygen and hydroxyl radicals and

inhibiting lipid peroxidation (Zhang 2014).

A study also showed that EA can alleviate the

production of new fat in the liver. Mice were injected

with mouse thymoma virus oncogene homologue (a

substance that can improve mouse sterol regulatory

element binding protein-1 and adipogenesis

regulatory factor). After EA intervention, the

transcription and translation of fatty acid synthase

(FASN) in mice were inhibited, reducing the

accumulation of lipids in mouse hepatocytes. And it

can alleviate the steatosis of human hepatoma cells

induced by oleic acid in vitro (Zhang 2019). 150mg /

kg EA treatment could significantly reduce the

activities of antioxidant enzymes cat, GSH Px, SOD

and T-AOC caused by 8-week D-gal diet. The

enzyme activities of cat and SOD returned to normal

level, and the enzyme activities of T-AOC exceeded

(Peng 2018).

3 CONCLUSIONS

The incidence rate of NAFLD is increasing year by

year due to unhealthy diet and work habits. There is

no definite drug for NAFLD, and there is a poor

compliance between bad eating habits and daily life

and regular exercise. However, many natural plant

polyphenols have shown the protective effect and

potential for NAFLD. Polyphenols and their

metabolites in human body can regulate lipid

metabolism, improve oxidative stress, slow down the

development of inflammatory response and insulin

resistance, reduce liver fat content, and enhance the

activity of antioxidant enzymes through circulation.

Most foods rich in polyphenols have low calories.

Eating more foods rich in polyphenols in daily diet,

common polyphenols and their sources are listed in

Table 1. Attention to a reasonable and balanced diet

of other micronutrients can effectively alleviate

NAFLD.

Table 1: Common polyphenols and main sources.

Polyphenol Group/Subgroup Source

Catechin Flavonoids

Green tea

(Masterjohn

2012)

Delphinidin Flavonoids

Blueberry,

Raspberry,

Strawberry

(Hosseinian

2007)

Pelargonidin Flavonoids

Blackberries,

Strawberries,

Plums

(Andersen

2013)

Cyanidin Flavonoids

Grapes,

Bilberry,

Berries,

Cherry,

Elderberry,

Hawthorn

(Tulio 2008)

Malvidin Flavonoids

Black rice,

Red grapes,

Blueberries

(Somerset

2008)

Curcumins Curcuminoids

Ginger, Ginger

plant (Ganjali

2017)

Resveratrol Stilbenes

Grapes,

Blueberries,

Peanuts,

Berries

(Brown 2010,

Charytoniuk

2016)

Protective Effect of Polyphenols on Non-alcoholic Fatty Liver Disease

125

Pterostilbene Stilbenes

Blueberries

(Paul 2010)

Piceatannol Stilbenes

Passion fruit,

Grapes (Lee

2019)

Ellagic acid Phenolic acids

Nuts,

Pomegranates,

Berries (

Kang

2016

)

Ferulic acid Phenolic acids

Grains,

Coffee,

Peanuts, Nuts

(Kumar 2014)

Cholorogenic

acid

Phenolic acids

Coffee, Beans,

Potato, Apple,

Prunes

(Nabavi 2019)

ACKNOWLEDGEMENTS

This work was supported by the Key Technology

Research and Development Program of Shandong

Province [grant numbers 2019QYTPY024,

2019YYSP019]; Key Technology Research and

Development Program of China [grant number 2020-

CXY45]; Spring Industry Leader Talent Support Plan

[grant numbers 2017035, 2019042]; Shandong

Taishan Leading Talent Project [grant numbers

LJNY202015, tscy20180507]; and Science,

Education, and Industry Integration Innovation pilot

project at Qilu University of Technology (Shandong

Academy of Sciences) [grant numbers 2020KJC-

YJ01, 2020KJC-GH10].

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