New insight and potential therapy for NAFLD: CYP2E1 and flavonoids

Wang, Kaiyue; Tan, Wangxiao; Liu, Xiao; Deng, Li; Huang, Lu; Wang, Xiaoying; Gao, Xiumei

doi:10.1016/j.biopha.2021.111326

Cited by 46 publications

(34 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Clinical trials have shown that vitamin E can ameliorate NAFLD by attenuating oxidative stress and inflammation (reviewed in [ 157 , 158 ]); however, the safety of prolonged vitamin E use is uncertain [ 159 , 160 , 161 ]. In addition to vitamin E, flavonoids have anti-inflammatory and antioxidant properties and reduce the expression of CYP2E1 (reviewed in [ 162 ]). For instance, quercetin and several saponins, alkaloids, terpenoids and polyphenols have been tested in vivo and in vitro and many have shown promise for NASH treatment (reviewed in [ 163 ]).…”

Section: Cyp2e1 In Nafldmentioning

confidence: 99%

CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload

Harjumäki

Pridgeon

Ingelman‐Sundberg

2021

IJMS

125

View full text Add to dashboard Cite

CYP2E1 is one of the fifty-seven cytochrome P450 genes in the human genome and is highly conserved. CYP2E1 is a unique P450 enzyme because its heme iron is constitutively in the high spin state, allowing direct reduction of, e.g., dioxygen, causing the formation of a variety of reactive oxygen species and reduction of xenobiotics to toxic products. The CYP2E1 enzyme has been the focus of scientific interest due to (i) its important endogenous function in liver homeostasis, (ii) its ability to activate procarcinogens and to convert certain drugs, e.g., paracetamol and anesthetics, to cytotoxic end products, (iii) its unique ability to effectively reduce dioxygen to radical species causing liver injury, (iv) its capability to reduce compounds, often generating radical intermediates of direct toxic or indirect immunotoxic properties and (v) its contribution to the development of alcoholic liver disease, steatosis and NASH. In this overview, we present the discovery of the enzyme and studies in humans, 3D liver systems and genetically modified mice to disclose its function and clinical relevance. Induction of the CYP2E1 enzyme either by alcohol or high-fat diet leads to increased severity of liver pathology and likelihood to develop ALD and NASH, with subsequent influence on the occurrence of hepatocellular cancer. Thus, fat-dependent induction of the enzyme might provide a link between steatosis and fibrosis in the liver. We conclude that CYP2E1 has many important physiological functions and is a key enzyme for hepatic carcinogenesis, drug toxicity and liver disease.

show abstract

Section: Cyp2e1 In Nafldmentioning

confidence: 99%

CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload

Harjumäki

Pridgeon

Ingelman‐Sundberg

2021

IJMS

125

View full text Add to dashboard Cite

show abstract

“…NAFLD, as the main manifestation and precursor of MetS in the liver, has complicated pathogenesis [ 249 ]. A series of previous studies have shown that CYP2E1 may be involved in excessive fat accumulation and aggravated oxidative stress-induced inflammation, leading to various liver cell damage and death [ 250 , 251 , 252 ]. Although only part of the polyphenols (including baicalin, quercetin) in NAFLD and MetS progression in regulating the expression of CYP2E1 and activity [ 80 , 88 , 91 ], a number of polyphenols (resveratrol and curcumin) interact with CYP2E1 in other diseases (e.g., alcohol-induced liver damage, chemically-induced HCC) [ 253 , 254 , 255 ].…”

Section: Other Issues Of Natural Polyphenolsmentioning

confidence: 99%

“…Although only part of the polyphenols (including baicalin, quercetin) in NAFLD and MetS progression in regulating the expression of CYP2E1 and activity [ 80 , 88 , 91 ], a number of polyphenols (resveratrol and curcumin) interact with CYP2E1 in other diseases (e.g., alcohol-induced liver damage, chemically-induced HCC) [ 253 , 254 , 255 ]. Accordingly, the role and molecular mechanism of flavonoids in CYP2E1 regulation still need to be further explored [ 252 ]. On the other hand, adiponectin is the most common adipokine known to be inversely associated with insulin resistance, lipid accumulation, inflammation, and NAFLD development [ 256 ].…”

Section: Other Issues Of Natural Polyphenolsmentioning

confidence: 99%

Natural Polyphenols in Metabolic Syndrome: Protective Mechanisms and Clinical Applications

Zhang

et al. 2021

IJMS

View full text Add to dashboard Cite

Metabolic syndrome (MetS) is a chronic disease, including abdominal obesity, dyslipidemia, hyperglycemia, and hypertension. It should be noted that the occurrence of MetS is closely related to oxidative stress-induced mitochondrial dysfunction, ectopic fat accumulation, and the impairment of the antioxidant system, which in turn further aggravates the intracellular oxidative imbalance and inflammatory response. As enriched anti-inflammatory and antioxidant components in plants, natural polyphenols exhibit beneficial effects, including improving liver fat accumulation and dyslipidemia, reducing blood pressure. Hence, they are expected to be useful in the prevention and management of MetS. At present, epidemiological studies indicate a negative correlation between polyphenol intake and MetS incidence. In this review, we summarized and discussed the most promising natural polyphenols (including flavonoid and non-flavonoid drugs) in the precaution and treatment of MetS, including their anti-inflammatory and antioxidant properties, as well as their regulatory functions involved in glycolipid homeostasis.

show abstract

“…NAFLD is a highly popular disorder with limited treatments [1]. Hence, finding an effective treatment is necessary [6]. Since most drugs may increase liver toxicity, it is important to select the appropriate drug therapy that able to cure NAFLD and other hepatic diseases [6].…”

Section: Introductionmentioning

confidence: 99%

“…Hence, finding an effective treatment is necessary [6]. Since most drugs may increase liver toxicity, it is important to select the appropriate drug therapy that able to cure NAFLD and other hepatic diseases [6]. An endogenous aminoguanidine compound -Agmatine (AGM) -is a decarboxylated product of L-arginine made from arginine-by-arginine decarboxylase [7].…”

Section: Introductionmentioning

confidence: 99%

Effect of Agmatine on Non-Alcoholic Fatty Liver Disease Induced by Type 2 Diabetes in Rats

Miski

Ahmad

Esmat

2021

JPRI

View full text Add to dashboard Cite

Aim: To determine the potential hepatoprotective effect of Agmatine (AGM) on NAFLD-induced by Type 2 diabetes mellitus (T2DM) in rats. Study design: Forty male Wistar rats weighing from (200 -250 g) were distributed at random into five groups (8 rats per group): group 1 as control; group 2 as untreated-T2DM; groups 3 & 4 as T2DM cotreated with AGM (40 & 80 mg/kg/d), while group 5 T2DM cotreated with Silymarin (100 mg/kg/d). Place and duration of study: Department of Pharmacology, Faculty of Medicine, king Abdul-Aziz University; between October 2020 and January 2021. Methodology: A rat model of T2DM with NAFLD complication was established by feeding rats with 10% fructose in drinking water and intraperitoneally injecting them with a single low dose of streptozotocin (STZ) (45mg/kg). The fasting blood glucose was detected, serum levels of hepatic biomarkers were all assessed. Moreover, histopathological examination was performed by hematoxylin and eosin (H&E) staining. Results: STZ induced T2DM in rats causes a significant (p<0.05, n=8) rise in serum levels of FBG, ALT, AST, TB, TC, TG, and LDL in comparison with the corresponding control group. Co-treatment with AGM (40 & 80 mg/kg) and silymarin significantly alleviated hyperglycemia and amended hepatic biomarkers that was reflected on improved histopathological changes. Conclusion: The current data suggest that oral AGM co-treatment could have a hepatoprotective effect against T2DM associated with NAFLD in rats. Further investigations are recommended to elucidate molecular mechanisms accountable for the useful effects of AGM on hepatocytes.

show abstract

New insight and potential therapy for NAFLD: CYP2E1 and flavonoids

Cited by 46 publications

References 99 publications

CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload

CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload

Natural Polyphenols in Metabolic Syndrome: Protective Mechanisms and Clinical Applications

Effect of Agmatine on Non-Alcoholic Fatty Liver Disease Induced by Type 2 Diabetes in Rats

Contact Info

Product

Resources

About