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      Silymarin: Unveiling its pharmacological spectrum and therapeutic potential in liver diseases—A comprehensive narrative review

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          Abstract

          Liver diseases, encompassing conditions such as cirrhosis, present a substantial global health challenge with diverse etiologies, including viral infections, alcohol consumption, and non‐alcoholic fatty liver disease (NAFLD). The exploration of natural compounds as therapeutic agents has gained traction, notably the herbal remedy milk thistle ( Silybum marianum), with its active extract, silymarin, demonstrating remarkable antioxidant and hepatoprotective properties in extensive preclinical investigations. It can protect healthy liver cells or those that have not yet sustained permanent damage by reducing oxidative stress and mitigating cytotoxicity. Silymarin, a natural compound with antioxidant properties, anti‐inflammatory effects, and antifibrotic activity, has shown potential in treating liver damage caused by alcohol, NAFLD, drug‐induced toxicity, and viral hepatitis. Legalon® is a top‐rated medication with excellent oral bioavailability, effective absorption, and therapeutic effectiveness. Its active component, silymarin, has antioxidant and hepatoprotective properties, Eurosil 85® also, a commercial product, has lipophilic properties enhanced by special formulation processes. Silymarin, during clinical trials, shows potential improvements in liver function, reduced mortality rates, and alleviation of symptoms across various liver disorders, with safety assessments showing low adverse effects. Overall, silymarin emerges as a promising natural compound with multifaceted hepatoprotective properties and therapeutic potential in liver diseases.

          Abstract

          A thorough examination of the substantiating evidence supporting its use as an adjunctive therapy for individuals grappling with liver‐related conditions.

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          Most cited references105

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          Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.

          Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression, and outcomes of NAFLD and nonalcoholic steatohepatitis (NASH). PubMed/MEDLINE were searched from 1989 to 2015 for terms involving epidemiology and progression of NAFLD. Exclusions included selected groups (studies that exclusively enrolled morbidly obese or diabetics or pediatric) and no data on alcohol consumption or other liver diseases. Incidence of hepatocellular carcinoma (HCC), cirrhosis, overall mortality, and liver-related mortality were determined. NASH required histological diagnosis. All studies were reviewed by three independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication, and study population. We used random-effects models to provide point estimates (95% confidence interval [CI]) of prevalence, incidence, mortality and incidence rate ratios, and metaregression with subgroup analysis to account for heterogeneity. Of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (95% CI: 22.10-28.65) with highest prevalence in the Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity (51.34%; 95% CI: 41.38-61.20), type 2 diabetes (22.51%; 95% CI: 17.92-27.89), hyperlipidemia (69.16%; 95% CI: 49.91-83.46%), hypertension (39.34%; 95% CI: 33.15-45.88), and metabolic syndrome (42.54%; 95% CI: 30.06-56.05). Fibrosis progression proportion, and mean annual rate of progression in NASH were 40.76% (95% CI: 34.69-47.13) and 0.09 (95% CI: 0.06-0.12). HCC incidence among NAFLD patients was 0.44 per 1,000 person-years (range, 0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77 per 1,000 (range, 0.33-1.77) and 11.77 per 1,000 person-years (range, 7.10-19.53) and 15.44 per 1,000 (range, 11.72-20.34) and 25.56 per 1,000 person-years (range, 6.29-103.80). Incidence risk ratios for liver-specific and overall mortality for NAFLD were 1.94 (range, 1.28-2.92) and 1.05 (range, 0.70-1.56).
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            The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases.

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              Burden of liver diseases in the world

              Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis is currently the 11th most common cause of death globally and liver cancer is the 16th leading cause of death; combined, they account for 3.5% of all deaths worldwide. Cirrhosis is within the top 20 causes of disability-adjusted life years and years of life lost, accounting for 1.6% and 2.1% of the worldwide burden. About 2 billion people consume alcohol worldwide and upwards of 75 million are diagnosed with alcohol-use disorders and are at risk of alcohol-associated liver disease. Approximately 2 billion adults are obese or overweight and over 400 million have diabetes; both of which are risk factors for non-alcoholic fatty liver disease and hepatocellular carcinoma. The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis. Liver transplantation is the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates. Though these numbers are sobering, they highlight an important opportunity to improve public health given that most causes of liver diseases are preventable.
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                Author and article information

                Contributors
                falasmari@kfu.edu.sa
                mabdulrahim@t.edu.pk , abdul.rahim@gcuf.edu.pk
                zongoeliasse@yahoo.fr
                Journal
                Food Sci Nutr
                Food Sci Nutr
                10.1002/(ISSN)2048-7177
                FSN3
                Food Science & Nutrition
                John Wiley and Sons Inc. (Hoboken )
                2048-7177
                16 February 2024
                May 2024
                : 12
                : 5 ( doiID: 10.1002/fsn3.v12.5 )
                : 3097-3111
                Affiliations
                [ 1 ] University Institute of Diet & Nutritional Sciences, Faculty of Allied Health Sciences The University of Lahore Lahore Pakistan
                [ 2 ] Department of Food and Nutrition Sciences, College of Agricultural and Food Sciences King Faisal University Al‐Ahsa Saudi Arabia
                [ 3 ] Department of Food Science, Faculty of Life Sciences Government College University Faisalabad Pakistan
                [ 4 ] Department of Food Science & Nutrition, Faculty of Medicine and Allied Health Sciences Times Institute Multan Pakistan
                [ 5 ] Laboratoire de Recherche et d'Enseignement en Santé et Biotechnologies Animales Université Nazi BONI Bobo Dioulasso Burkina Faso
                Author notes
                [*] [* ] Correspondence

                Muhammad Abdul Rahim, Department of Food Science, Faculty of Life Sciences, Government College University, Faisalabad 38000, Pakistan.

                Email: mabdulrahim@ 123456t.edu.pk and abdul.rahim@ 123456gcuf.edu.pk

                Fahad Al‐Asmari, Department of Food and Nutrition Sciences, College of Agricultural and Food Sciences, King Faisal University, Al‐Ahsa 31982, Saudi Arabia.

                Email: falasmari@ 123456kfu.edu.sa

                Eliasse Zongo, Laboratoire de Recherche et d'Enseignement en Santé et Biotechnologies Animales, Université Nazi BONI, Bobo Dioulasso 01 BP 1091, Burkina Faso.

                Email: zongoeliasse@ 123456yahoo.fr

                Author information
                https://orcid.org/0000-0003-4253-2796
                https://orcid.org/0000-0001-9885-8301
                Article
                FSN34010 FSN3-2023-11-2456.R1
                10.1002/fsn3.4010
                11077231
                38726410
                3885ad54-582a-44e8-963f-7c17e0a661b1
                © 2024 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 January 2024
                : 11 November 2023
                : 24 January 2024
                Page count
                Figures: 5, Tables: 1, Pages: 15, Words: 11936
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                May 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.2 mode:remove_FC converted:08.05.2024

                fatty liver disease,milk thistle,non‐alcoholic fatty liver disease,silibinin,silymarin

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