Prioritizing drug targets for non-alcoholic fatty liver disease based on comorbidity network analysis

The estimated prevalence of NonAlcoholic Fatty Liver Disease in the general population in western countries is about 30%, but it is higher among obese and diabetic people. It is likely that more sophisticated approaches are required to understand its pathogenesis and to develop drug targets. In the meantime, the range of associations between NAFLD and other illnesses broadens. Although association does not mean causation, the link between some diseases and NAFLD suggests a common mechanism.

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Network Pharmacology Exploration Reveals Anti-Apoptosis as a Common Therapeutic Mechanism for Non-Alcoholic Fatty Liver Disease Treated with Blueberry Leaf Polyphenols

Nutrients ◽

10.3390/nu13114060 ◽

2021 ◽

Vol 13 (11) ◽

pp. 4060

Author(s):

Cai-Ren Wang ◽

Hong-Wei Chen ◽

Yan Li ◽

Ming-Yue Zhou ◽

Vincent Kam-Wai Wong ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Drug Targets ◽

Cell Model ◽

Interaction Network ◽

Network Pharmacology ◽

Alcoholic Fatty Liver ◽

Apoptosis Pathway ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease characterized by excessive fat accumulation in the liver. The aim of this study is to elucidate the multi-target mechanism of polyphenols in blueberry leaves (PBL) on NAFLD by network pharmacology and to validate its results via biological experiments. Twenty constituents in PBL were preliminarily determined by liquid chromatography-tandem mass spectrometry. Subsequently, 141 predicted drug targets and 1226 targets associated with NAFLD were retrieved from public databases, respectively. The herb-compound-target network and the target protein–protein interaction network (PPI) were established through Cytoscape software, and four compounds and 53 corresponding targets were identified. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to explore the biological processes of the predicted genes. The results of cell experiments demonstrated that PBL could significantly improve the viability of the NAFLD cell model, and the protein expressions of caspase-3 and Bcl-2 were consistent with the expected mechanism of action of PBL. Those results systematically revealed that the multi-target mechanism of PBL against NAFLD was related to the apoptosis pathway, which could bring deeper reflections into the hepatoprotective effect of PBL.

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Strategies of Cell Signaling and Critical Focus on Etiology of Hepatocellular Carcinoma

Biointerface Research in Applied Chemistry ◽

10.33263/briac124.51875198 ◽

2021 ◽

Vol 12 (4) ◽

pp. 5187-5198

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Fatty Liver ◽

Signaling Pathways ◽

Fatty Liver Disease ◽

Drug Targets ◽

Incidence Rates ◽

Therapeutic Drug ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Hepatocellular carcinoma is an atypical biological cell process that is frequently identified at an advanced stage, with no promising therapeutic options available. Hepatocarcinogenesis is connected to a range of cellular signaling pathways, notably Wnt-β-catenin (canonical Wnt pathway), nuclear factor-B, and YAP-HIPPO (Yes-associated protein Salvador-Warts-Hippo pathway); each of these is considered a potential pharmacological candidate. Inflammation in the liver for a long time and damage play a big role in the incidence and development of HCC. HCC incidence rates go up by the many variables such as sex, age, ethnicity, and demographics are all factors to consider, and the leading causes of infection by the chronic or hepatitis B virus (HBV), hepatitis C virus (HCV), nutrient pollutants, ecological poisons, tobacco smoldering, and genetic disorders, which are all carcinogens. In this review, we expanded on our existing empathetic of the signaling pathways involved in the development and genesis of HCC. We also encapsulated the etiology of HCC, with a focus on HCC triggered by non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD). In this review, we forecasted potential therapeutic drug targets.

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Vitamin D levels are not associated with non-alcoholic fatty liver disease severity in a Brazilian population

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000667 ◽

2020 ◽

pp. 1-8

Author(s):

Jeniffer Danielle M. Dutra ◽

Quelson Coelho Lisboa ◽

Silvia Marinho Ferolla ◽

Carolina Martinelli M. L. Carvalho ◽

Camila Costa M. Mendes ◽

...

Keyword(s):

Vitamin D ◽

Liver Disease ◽

Fatty Liver ◽

Disease Severity ◽

Fatty Liver Disease ◽

Hypovitaminosis D ◽

Alcoholic Fatty Liver ◽

Vitamin D Levels ◽

The Mean ◽

Alcoholic Fatty Liver Disease

Abstract. Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.

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Non-Alcoholic Fatty Liver Disease in Overweight Children and its Relationship with Retinol Serum Levels

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.78.1.27 ◽

2008 ◽

Vol 78 (1) ◽

pp. 27-32 ◽

Cited By ~ 15

Author(s):

Suano de Souza ◽

Silverio Amancio ◽

Saccardo Sarni ◽

Sacchi Pitta ◽

Fernandes ◽

...

Keyword(s):

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Lipid Profile ◽

Fatty Liver Disease ◽

Thiobarbituric Acid ◽

Serum Levels ◽

Control Group ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Objectives: To evaluate the frequency of non-alcoholic fatty liver disease, the retinol serum levels, lipid profile, and insulin resistance in overweight/obese children. To relate these biochemical variables with the risk of this disease in the population studied. Methods: The study was cross-sectional and prospective, with 46 overweight/obese school children (28 female, 18 male; mean age 8.6 years). The control group consisted of 45 children, paired by age and gender. Hepatic steatosis, evaluated by ultrasound, was classified as normal, mild, moderate, or severe. Also evaluated were serum retinol levels; thiobarbituric acid reactive substances; lipid profile; and fasting glucose and serum insulin levels, used for the calculation of the Homeostasis Model Assessment. Results: Hepatic ultrasound alterations were found in 56.5% and 48,9% of the overweight/obese and control group children, respectively. Presence of obesity was associated with high levels of triglycerides (OR = 4.6; P = 0.002). In the studied children, the risk of steatosis was related to a trend to a higher percentage of retinol inadequacy (OR = 2.8; p = 0.051); there was no association with thiobarbituric acid reactive substances, lipid profile, or insulin resistance. Conclusions: The high frequency of non-alcoholic fatty liver disease in both groups, evaluated by hepatic ultrasound, in low-socioeconomic level children, independent of nutritional condition and without significant association with insulin resistance, emphasizes that especially in developing countries, other risk factors such as micronutrient deficiencies (e.g. vitamin A) are involved.

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