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Pharmaceuticals
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Pharmacological Targets for the Treatment of Nonalcoholic Fatty Liver Disease
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Pharmacological Targets for the Treatment of Nonalcoholic Fatty Liver Disease

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (15 January 2023) | Viewed by 9679

Special Issue Editor

Prof. Dr. Ahmed E Abdel Moneim

E-Mail Website
Guest Editor
Department of Zoology and Entomology, Helwan University, Cairo, Egypt
Interests: physiology; animal models; toxicology

Special Issue Information

Dear Colleagues,

Non-alcoholic fatty liver disease (NAFLD) is described as the existence of fat vesicles (mostly triglycerides) in hepatocytes, encompassing the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD  comprises non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). NAFLD is linked to an increased risk of liver-related morbidity and death, as well as cardiovascular disease, diabetes, and non-liver-related cancer. NAFLD is linked to obesity, glucose homeostasis abnormalities, and metabolic syndrome (but it can also be present in persons who do not have symptoms of metabolic syndrome). This Special Issue aims to unravel the process of NAFLD, explore its novel signaling pathways and regulatory mechanisms, and gain insights into the NAFLD complications in the human body and health, which will help us to develop new drugs and methods to combat NAFLD-related diseases. We welcome original research and reviews on new drugs and strategies targeting NAFLD.

Prof. Dr. Ahmed E Abdel Moneim
Guest Editor

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. Pharmaceuticals 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 2900 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

  • NAFLD processes
  • drug targeting and design
  • pathogenic links between NAFLD and various aspects of human health and disease, including liver diseases, diabetes, cancer, and heart disease
  • improving the current strategy in designing new drugs targeting NAFLD
  • identification of bioactive compounds from natural sources
  • improving the current strategies for drug delivery to target NAFLD

Published Papers (4 papers)

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Research

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15 pages, 1250 KiB  
Article
The Impact of an SGLT2 Inhibitor versus Ursodeoxycholic Acid on Liver Steatosis in Diabetic Patients
by Sahar H. Elhini, Engy A. Wahsh, Ahmed A. Elberry, Nadia F. El Ameen, Ahmed Abdelfadil Saedii, Shereen Mahmoud Refaie, Asmaa A. Elsayed and Hoda M. Rabea
Pharmaceuticals 2022, 15(12), 1516; https://doi.org/10.3390/ph15121516 - 05 Dec 2022
Cited by 7 | Viewed by 2120
Abstract
Non-alcoholic fatty liver disease (NAFLD) is related to metabolic syndrome via insulin resistance, where preventing disease progression is crucial in the management process. The study included 240 NAFLD patients with type 2 diabetes who were randomly allocated into empagliflozin 25 mg (EMPA group), [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is related to metabolic syndrome via insulin resistance, where preventing disease progression is crucial in the management process. The study included 240 NAFLD patients with type 2 diabetes who were randomly allocated into empagliflozin 25 mg (EMPA group), ursodeoxycholic acid 250 mg (UDCA group), or the control group (placebo). The study outcomes included: changes in liver fat content (LFC; %) (utilizing the Dixon-based MRI-PDFF approach), liver enzymes, lipid and glycemic profiles, FIB-4 index, and non-alcoholic fatty liver score (NFS). All endpoints were assessed at baseline and after 6 months. EMPA outperformed UDCA and placebo in decreasing LFC (−8.73% vs. −5.71% vs. −1.99%; p < 0.0001). In post-treatment ultrasound images and MRI-PDFF calculations, more patients had normal fatty liver grade (no steatosis or LFC < 6.5%) with EMPA compared to UDCA. EMPA and UDCA showed significant regression in the FIB-4 index (−0.34 vs. −0.55; p = 0.011) and NFS scores (−1.00 vs. −1.11; p = 0.392), respectively. UDCA achieved higher reductions in insulin resistance than EMPA (p = 0.03); however, only EMPA significantly increased beta-cell function (54.20; p = 0.03). When exploring the differences between the two drugs, EMPA was better in decreasing LFC (%), while UDCA achieved higher reductions in liver fibrosis scores. Both showed a similar safety profile in managing liver steatosis. Full article
(This article belongs to the Special Issue Pharmacological Targets for the Treatment of Nonalcoholic Fatty Liver Disease)
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17 pages, 2555 KiB  
Article
Lycopene Modulates Oxidative Stress and Inflammation in Hypercholesterolemic Rats
by Tarfa Albrahim
Pharmaceuticals 2022, 15(11), 1420; https://doi.org/10.3390/ph15111420 - 17 Nov 2022
Cited by 7 | Viewed by 1883
Abstract
The complicated disorder of hypercholesterolemia has several underlying factors, including genetic and lifestyle factors. Low LDL cholesterol and elevated serum total cholesterol are its defining features. A carotenoid with antioxidant quality is lycopene. Examining lycopene activity in an animal model of hypercholesterolemia induced [...] Read more.
The complicated disorder of hypercholesterolemia has several underlying factors, including genetic and lifestyle factors. Low LDL cholesterol and elevated serum total cholesterol are its defining features. A carotenoid with antioxidant quality is lycopene. Examining lycopene activity in an animal model of hypercholesterolemia induced using food was the aim of this investigation. Triglycerides, LDL cholesterol, HDL cholesterol, and plasma total cholesterol were all measured. Biomarkers of renal and cardiac function were also examined. Apoptotic indicators, pro-inflammatory markers, and oxidative stress were also assessed. Additionally, the mRNA expression of paraoxonase 1 (PON-1), peroxisome proliferator-activated receptor gamma (PPAR-γ), and PPAR-γ coactivator 1 alpha (PGC-1α) in cardiac and renal tissues was examined. Rats showed elevated serum lipid levels, renal and cardiac dysfunction, significant oxidative stress, and pro-inflammatory and apoptotic markers at the end of the study. Treatment with lycopene significantly corrected and restored these changes. Additionally, lycopene markedly increased the mRNA expression of PGC-1α and PON-1, and decreased PPAR-γ expression. It was determined that lycopene has the capacity to modulate the PPAR-γ and PON-1 signaling pathway in order to preserve the cellular energy metabolism of the heart and kidney, which in turn reduces tissue inflammatory response and apoptosis. According to these findings, lycopene may be utilized as a medication to treat hypercholesterolemia. However, further studies should be conducted first to determine the appropriate dose and any adverse effects that may appear after lycopene usage in humans. Full article
(This article belongs to the Special Issue Pharmacological Targets for the Treatment of Nonalcoholic Fatty Liver Disease)
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15 pages, 2351 KiB  
Article
The Impact of Dietary Consumption of Palm Oil and Olive Oil on Lipid Profile and Hepatocyte Injury in Hypercholesterolemic Rats
by Tarfa Albrahim, Maram H. M. Alotaibi, Norah M. M. Altamimi, Atheer M. A. Albariqi, Lamees A. O. Alqarni, Sara N. A. Alassaf, Hisham S. Aloudah, Mohammed Alahmed, Ahmad T. Almnaizel, Maha R. Aldraihem and Mona Alonazi
Pharmaceuticals 2022, 15(9), 1103; https://doi.org/10.3390/ph15091103 - 04 Sep 2022
Cited by 3 | Viewed by 2381
Abstract
A metabolic disease called hypercholesterolemia is connected to both oxidative damage and inflammation. The goal of the current investigation was to determine if olive oil and palm oil could prevent hypercholesterolemia-induced oxidative stress in the liver of rats fed a high-cholesterol diet (HCD). [...] Read more.
A metabolic disease called hypercholesterolemia is connected to both oxidative damage and inflammation. The goal of the current investigation was to determine if olive oil and palm oil could prevent hypercholesterolemia-induced oxidative stress in the liver of rats fed a high-cholesterol diet (HCD). The experimental mice were given HCD for three months while also receiving 0.5 mL/kg of either palm or olive oil. Serum triglycerides, total cholesterol, LDL cholesterol, vLDL cholesterol, and the atherogenic index all significantly increased in HCD-fed rats, while HDL cholesterol significantly dropped. Additionally, HCD caused a notable rise in proinflammatory cytokines and serum transaminases in liver tissue. Additionally, HCD significantly increased the production of nitric oxide and lipid peroxidation in the liver while decreasing antioxidant enzymes. Treatment with palm and olive oils dramatically reduced the levels of pro-inflammatory cytokines and lipid peroxidation, improved antioxidant defenses, and considerably improved liver function indicators. Additionally, the examined oils dramatically decreased the expression of fatty acid synthase (FAS) in the liver of rats receiving HCD. In conclusion, HCD-fed rats exhibit significant antihyperlipidemic and cholesterol-lowering benefits from palm and olive oils. The improved antioxidant defenses, lower inflammation and lipid peroxidation, and altered hepatic FAS mRNA expression were the main mechanisms by which palm and olive oils produced their advantageous effects. Full article
(This article belongs to the Special Issue Pharmacological Targets for the Treatment of Nonalcoholic Fatty Liver Disease)
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Review

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16 pages, 1735 KiB  
Review
The STING in Non-Alcoholic Fatty Liver Diseases: Potential Therapeutic Targets in Inflammation-Carcinogenesis Pathway
by Juan Lv, Chunlei Xing, Yuhong Chen, Huihui Bian, Nanning Lv, Zhibin Wang, Mingming Liu and Li Su
Pharmaceuticals 2022, 15(10), 1241; https://doi.org/10.3390/ph15101241 - 09 Oct 2022
Cited by 3 | Viewed by 2763
Abstract
Non-alcoholic fatty liver disease (NAFLD), an important chronic disease, is one of the major causes of high mortality and creates a substantial financial burden worldwide. The various immune cells in the liver, including macrophages, NK cells, dendritic cells, and the neutrophils involved in [...] Read more.
Non-alcoholic fatty liver disease (NAFLD), an important chronic disease, is one of the major causes of high mortality and creates a substantial financial burden worldwide. The various immune cells in the liver, including macrophages, NK cells, dendritic cells, and the neutrophils involved in the innate immune response, trigger inflammation after recognizing the damage signaled from infection or injured cells and tissues. The stimulator of interferon genes (STING) is a critical molecule that binds to the cyclic dinucleotides (CDNs) generated by the cyclic GMP-AMP synthase (cGAS) to initiate the innate immune response against infection. Previous studies have demonstrated that the cGAS-STING pathway plays a critical role in inflammatory, auto-immune, and anti-viral immune responses. Recently, studies have focused on the role of STING in liver diseases, the results implying that alterations in its activity may be involved in the pathogenesis of liver disorders. Here, we summarize the function of STING in the development of NAFLD and present the current inhibitors and agonists targeting STING. Full article
(This article belongs to the Special Issue Pharmacological Targets for the Treatment of Nonalcoholic Fatty Liver Disease)
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