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Biomolecules
Special Issues
Nonalcoholic Fatty Liver Disease: From Molecular Mechanisms to Therapeutic Approaches
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Nonalcoholic Fatty Liver Disease: From Molecular Mechanisms to Therapeutic Approaches

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 3540

Special Issue Editors

Dr. Yumin Dai

E-Mail Website
Guest Editor
Department of Chemistry and Virginia Tech Center for Drug Discovery, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
Interests: peptides; secondary metabolites; nutraceuticals; interactions between small molecules; enzymes; obesity; cytotoxicity; anti-HIV; analytical methods; LC-MS; NMR
Special Issues, Collections and Topics in MDPI journals
Dr. Martina Beretta

E-Mail Website
Guest Editor
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia
Interests: non-alcoholic fatty liver disease; diabetes; mitochondrial uncouplers; mouse models of metabolic disease; obesity; energy metabolism

Special Issue Information

Dear Colleagues,

Nonalcoholic fatty liver disease, or NAFLD, refers to a liver problem that affects human beings who drink little to no alcohol, and it is becoming more common, especially in Middle Eastern and Western countries, with increasing rates of obesity. In recent years, great efforts have been made to investigate the pathogenesis of NAFLD; accordingly, a large quantity of biomolecules (small synthetic molecules, natural products, active peptides, oligonucleotide, etc.) with decent activities have been discovered as promising therapeutics through a variety of mechanisms, such as mitochondrial uncouplers, fibroblast growth factor activators, etc. Therefore, this Special Issue aims to publish submissions covering either the identification of biomolecules with promising therapeutic effects or mechanistic studies of biomolecules targeting NAFLD.

Dr. Yumin Dai
Dr. Martina Beretta
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nonalcoholic fatty liver disease (NAFLD)
  • non-alcoholic steatohepatitis (NASH)
  • reactive oxygen species
  • mitochondria
  • lipotoxicity

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Published Papers (3 papers)

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Research

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16 pages, 2164 KiB  
Article
The Hepatoprotective Properties of Gentiopicroside, Sweroside, and Swertiamarin Against Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
by Anthony O. Boateng, Vinood B. Patel and S. W. Annie Bligh
Biomolecules 2025, 15(5), 726; https://doi.org/10.3390/biom15050726 - 16 May 2025
Viewed by 226
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disease characterised by the accumulation of fat in the liver. It is estimated that 30–38% of the world’s adult population have MASLD, making it the most prevalent global chronic liver disease. Due to a [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disease characterised by the accumulation of fat in the liver. It is estimated that 30–38% of the world’s adult population have MASLD, making it the most prevalent global chronic liver disease. Due to a lack of a therapy for MASLD, treatment has been mainly focussed on managing the conditions associated with the disease such as obesity, diabetes mellitus, and hyperlipidaemia. This study aimed to investigate the role played by Gentiana phytochemicals including the following: gentiopicroside, sweroside, and swertiamarin, in promoting hepatocyte protection against the cytotoxic effects of fatty acids. Gentiana species such as lutea, macrophylla, rigescens, and scabra are known to protect and enhance hepatocyte viability via their antioxidant, anti-inflammatory, and bitter components including the following: amarogentin gentianine, iso-orientin, swertiamarin, gentiopicroside, and sweroside. In this study, HepG2 cells pre-treated with phytochemicals gentiopicroside, sweroside, swertiamarin, and silymarin followed by an exposure to arachidonic acid (10, 30, 50 and 80 µM) were assessed for cell viability via MTT, mitochondrial function via seahorse assay, ROS levels via DCF assay, and annexin V-FITC for apoptosis. THLE-2 cells were also assayed for validation. The phytochemicals tested improved ATP production notably gentiopicroside, which improved ATP production by over 60% compared to untreated hepatocytes. Significant hepatocyte protection against lipotoxicity leading to apoptosis was also observed in gentiopicroside in the presence of 30 µM arachidonic acid with apoptosis reduced by over 50%. ROS production was reduced up to 60% by the pre-treatment of HepG2 cells with 20 µM, gentiopicroside, sweroside, swertiamarin, and silymarin, with the highest reduction observed in swertiamarin. It was concluded that phytochemicals gentiopicroside, sweroside, and swertiamarin play key roles in the hepatocyte protection against the cytotoxic effects of fatty acids. This protection is conferred by enhancing mitochondrial function in terms of increasing the maximal respiratory capacity in response to a high influx of fatty acids, promoting ATP production as well as scavenging ROS produced as a result of high fatty acid influx and increased mitochondrial respiration. Highlights: Gentiopicroside may minimise lipotoxicity leading to apoptosis and necrosis in hepatocytes in the presence of arachidonic acid. A pre-treatment of hepatocytes with phytochemicals, namely gentiopicroside, sweroside, and silymarin provides a degree of protection which may be attributed to the enhancement of mitochondrial function. Sweroside, silymarin, and swertiamarin may protect HepG2 and THLE-2 cells by scavenging ROS produced by arachidonic acid and the mitochondrial electron transport chain. Full article
(This article belongs to the Special Issue Nonalcoholic Fatty Liver Disease: From Molecular Mechanisms to Therapeutic Approaches)
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Review

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25 pages, 722 KiB  
Review
Racial and Ethnic Disparities in NAFLD: Harnessing Epigenetic and Gut Microbiota Pathways for Targeted Therapeutic Approaches
by Mohamed Zaiou and Olivier Joubert
Biomolecules 2025, 15(5), 669; https://doi.org/10.3390/biom15050669 - 5 May 2025
Viewed by 265
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern, impacting approximately 32.4% of the worldwide population. As a disease linked to metabolic dysfunction, NAFLD continues to rise alongside global increases in obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. There [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern, impacting approximately 32.4% of the worldwide population. As a disease linked to metabolic dysfunction, NAFLD continues to rise alongside global increases in obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. There is considerable evidence indicating that NAFLD disproportionately affects racial, ethnic, and minority groups, although the exact reasons for these disparities remain elusive. Contributing factors to this disease may include socioeconomic status, cultural influences, stress, genetic factors, and lifestyle choices. Emerging evidence suggests that these causal factors could influence epigenetic mechanisms, particularly DNA methylation and histone modifications, as well as the composition and diversity of gut microbiota. Nevertheless, there is a scarcity of research that comprehensively examines the interplay between epigenetic changes and gut microbiome variations in relation to NAFLD disparities across different racial and ethnic populations globally. This paper intends to (i) explore the connections between NAFLD, ethnic disparities, gut microbiota composition, and epigenetic alterations, while reviewing pertinent studies that illustrate how these factors contribute to health inequities among various ethnic groups impacted by this disease; (ii) explore potential therapeutic targets and biomarkers to advance the management of NAFLD; and (iii) provide insights to enhance our understanding of the mechanisms associated with this disease, thereby promoting further research in this field. Advancements in this area are anticipated to enhance our understanding of disease susceptibilities in at-risk groups and to provide new therapeutic options for NAFLD and its associated complications. Full article
(This article belongs to the Special Issue Nonalcoholic Fatty Liver Disease: From Molecular Mechanisms to Therapeutic Approaches)
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40 pages, 1249 KiB  
Review
Drug Advances in NAFLD: Individual and Combination Treatment Strategies of Natural Products and Small-Synthetic-Molecule Drugs
by Xing Wan, Jingyuan Ma, He Bai, Xuyang Hu, Yanna Ma, Mingjian Zhao, Jifeng Liu and Zhijun Duan
Biomolecules 2025, 15(1), 140; https://doi.org/10.3390/biom15010140 - 17 Jan 2025
Cited by 2 | Viewed by 2496
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease and is closely associated with metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. However, effective treatment strategies for NAFLD are still lacking. In recent years, [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease and is closely associated with metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. However, effective treatment strategies for NAFLD are still lacking. In recent years, progress has been made in understanding the pathogenesis of NAFLD, identifying multiple therapeutic targets and providing new directions for drug development. This review summarizes the recent advances in the treatment of NAFLD, focusing on the mechanisms of action of natural products, small-synthetic-molecule drugs, and combination therapy strategies. This review aims to provide new insights and strategies in treating NAFLD. Full article
(This article belongs to the Special Issue Nonalcoholic Fatty Liver Disease: From Molecular Mechanisms to Therapeutic Approaches)
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