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      Bioactive flavonoids metabolites in citrus species: their potential health benefits and medical potentials

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          Abstract

          Citrus flavonoids are naturally occurring phytochemicals widely present in the peels and pulps of citrus fruits. They exhibit a wide range of biological activities, including antioxidant, anti-inflammatory, hypoglycemic, lipid-lowering, antimicrobial, and gut-protective effects. These metabolites show great potential in improving metabolic syndromes such as diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases. Additionally, citrus flavonoids have demonstrated significant effects in inhibiting pancreatic lipase activity, regulating lipid metabolism, and enhancing intestinal barrier function. Advances in extraction and purification techniques have further promoted their applications in the fields of food, medicine, and functional materials. This review systematically summarizes the types, bioactivities, and mechanisms of action of citrus flavonoids, providing scientific evidence for their research and development.

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          Most cited references53

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          NAFLD: a multisystem disease.

          Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that is predicted to become also the most frequent indication for liver transplantation by 2030. Over the last decade, it has been shown that the clinical burden of NAFLD is not only confined to liver-related morbidity and mortality, but there is now growing evidence that NAFLD is a multisystem disease, affecting extra-hepatic organs and regulatory pathways. For example, NAFLD increases risk of type 2 diabetes mellitus (T2DM), cardiovascular (CVD) and cardiac diseases, and chronic kidney disease (CKD). Although the primary liver pathology in NAFLD affects hepatic structure and function to cause morbidity and mortality from cirrhosis, liver failure and hepatocellular carcinoma, the majority of deaths among NAFLD patients are attributable to CVD. This narrative review focuses on the rapidly expanding body of clinical evidence that supports the concept of NAFLD as a multisystem disease. The review discusses the factors involved in the progression of liver disease in NAFLD and the factors linking NAFLD with other extra-hepatic chronic diseases, such as T2DM, CVD, cardiac diseases and CKD. The review will not discuss NAFLD treatments as these are discussed elsewhere in this issue of the Journal. For this review, PubMed was searched for articles using the keywords "non-alcoholic fatty liver disease" or "fatty liver" combined with "diabetes", "cardiovascular (or cardiac) disease", "cardiovascular mortality" or "chronic kidney disease" between 1990 and 2014. Articles published in languages other than English were excluded.
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            The global burden of IBD: from 2015 to 2025.

            Over 1 million residents in the USA and 2.5 million in Europe are estimated to have IBD, with substantial costs for health care. These estimates do not factor in the 'real' price of IBD, which can impede career aspirations, instil social stigma and impair quality of life in patients. The majority of patients are diagnosed early in life and the incidence continues to rise; therefore, the effect of IBD on health-care systems will rise exponentially. Moreover, IBD has emerged in newly industrialized countries in Asia, South America and Middle East and has evolved into a global disease with rising prevalence in every continent. Understanding the worldwide epidemiological patterns of IBD will prepare us to manage the burden of IBD over time. The goal of this article is to establish the current epidemiology of IBD in the Western world, contrast it with the increase in IBD in newly industrialized countries and forecast the global effects of IBD in 2025.
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              Global Perspectives on Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis

              Over the past 2 decades, nonalcoholic fatty liver disease (NAFLD) has grown from a relatively unknown disease to the most common cause of chronic liver disease in the world. In fact, 25% of the world's population is currently thought to have NAFLD. Nonalcoholic steatohepatitis (NASH) is the subtype of NAFLD that can progress to cirrhosis, hepatocellular carcinoma (HCC), and death. NAFLD and NASH are not only found in adults-there is also a high prevalence of these diseases in children and adolescents. Because of the close association of NAFLD with type 2 diabetes (T2DM) and obesity, the latest models predict that the prevalence of NAFLD and NASH will increase, causing a tremendous clinical and economic burden and poor patient-reported outcomes. Nonetheless, there is no accurate noninvasive method to detect NASH, and treatment of this disease is limited to lifestyle modifications. To examine the state of NAFLD among different regions and understand the global trajectory of this disease, an international group of experts came together during the 2017 American Association for the Study of Liver Diseases Global NAFLD Forum. We provide a summary of this forum and an assessment of the current state of NAFLD and NASH worldwide.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2933017/overviewRole:
                Role:
                URI : https://loop.frontiersin.org/people/742045/overviewRole:
                Role: Role:
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                03 March 2025
                2025
                : 16
                : 1552171
                Affiliations
                [1] 1 The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) , Hangzhou, China
                [2] 2 Sichuan Provincial Women’s and Children’s Hospital , The Affiliated Women’s and Children’s Hospital of Chengdu Medical College , Chengdu, China
                [3] 3 School of Life Sciences , Zhejiang Chinese Medical University , Hangzhou, China
                Author notes

                Edited by: Alessandra Durazzo, Council for Agricultural Research and Economics, Italy

                Reviewed by: Inas Youssef Younis, Cairo University, Egypt

                *Correspondence: Zheng Chen, 15757872837@ 123456163.com
                [ † ]

                These authors have contributed equally to this work

                Article
                1552171
                10.3389/fphar.2025.1552171
                11911525
                40098613
                743ee9c8-3582-48d8-b30a-5ff1b453b20c
                Copyright © 2025 Xu, He, He and Chen.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 December 2024
                : 03 February 2025
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Zhejiang Provincial Natural Science Foundation of China (Grant No. LGF22H290001), the Fund of State Administration of Traditional Chinese Medicine of Zhejiang Province (Grant No. 2023ZR016 and 2023ZL419), the Fund of Zhejiang Chinese Medical University (Grant No. 2021JKJNTZ021B).
                Categories
                Pharmacology
                Mini Review
                Custom metadata
                Ethnopharmacology

                Pharmacology & Pharmaceutical medicine
                citrus,flavonoids,bioactivities,mechanisms of action,extraction techniques,health benefits

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