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      • Record: found
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      Natural products in atherosclerosis therapy by targeting PPARs: a review focusing on lipid metabolism and inflammation

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          Abstract

          Inflammation and dyslipidemia are critical inducing factors of atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and control the expression of multiple genes that are involved in lipid metabolism and inflammatory responses. However, synthesized PPAR agonists exhibit contrary therapeutic effects and various side effects in atherosclerosis therapy. Natural products are structural diversity and have a good safety. Recent studies find that natural herbs and compounds exhibit attractive therapeutic effects on atherosclerosis by alleviating hyperlipidemia and inflammation through modulation of PPARs. Importantly, the preparation of natural products generally causes significantly lower environmental pollution compared to that of synthesized chemical compounds. Therefore, it is interesting to discover novel PPAR modulator and develop alternative strategies for atherosclerosis therapy based on natural herbs and compounds. This article reviews recent findings, mainly from the year of 2020 to present, about the roles of natural herbs and compounds in regulation of PPARs and their therapeutic effects on atherosclerosis. This article provides alternative strategies and theoretical basis for atherosclerosis therapy using natural herbs and compounds by targeting PPARs, and offers valuable information for researchers that are interested in developing novel PPAR modulators.

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          Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction

          Jean-Claude Tardif, Simon Kouz, David D. Waters … (2020)
          Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis.
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            PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD

            Barbara Gross, Michal Pawlak, Philippe Lefebvre … (2017)
            Obesity is a worldwide epidemic that predisposes individuals to cardiometabolic complications, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), which are all related to inappropriate ectopic lipid deposition. Identification of the pathogenic molecular mechanisms and effective therapeutic approaches are highly needed. The peroxisome proliferator-activated receptors (PPARs) modulate several biological processes that are perturbed in obesity, including inflammation, lipid and glucose metabolism and overall energy homeostasis. Here, we review how PPARs regulate the functions of adipose tissues, such as adipogenesis, lipid storage and adaptive thermogenesis, under healthy and pathological conditions. We also discuss the clinical use and mechanism of PPAR agonists in the treatment of obesity comorbidities such as dyslipidaemia, T2DM and NAFLD. First generation PPAR agonists, primarily those acting on PPARγ, are associated with adverse effects that outweigh their clinical benefits, which led to the discontinuation of their development. An improved understanding of the physiological roles of PPARs might, therefore, enable the development of safe, new PPAR agonists with improved therapeutic potential.
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              PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties.

              M Bouhlel, Bruno Derudas, Elena Rigamonti … (2007)
              Th1 cytokines promote monocyte differentiation into proatherogenic M1 macrophages, while Th2 cytokines lead to an "alternative" anti-inflammatory M2 macrophage phenotype. Here we show that in human atherosclerotic lesions, the expression of M2 markers and PPARgamma, a nuclear receptor controlling macrophage inflammation, correlate positively. Moreover, PPARgamma activation primes primary human monocytes into M2 differentiation, resulting in a more pronounced anti-inflammatory activity in M1 macrophages. However, PPARgamma activation does not influence M2 marker expression in resting or M1 macrophages, nor does PPARgamma agonist treatment influence the expression of M2 markers in atherosclerotic lesions, indicating that only native monocytes can be primed by PPARgamma activation to an enhanced M2 phenotype. Furthermore, PPARgamma activation significantly increases expression of the M2 marker MR in circulating peripheral blood mononuclear cells. These data demonstrate that PPARgamma activation skews human monocytes toward an anti-inflammatory M2 phenotype.
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                Author and article information

                Contributors
                Yan Zhang: URI : https://loop.frontiersin.org/people/1832533/overviewRole: Role:
                Xue-Ying Zhang: Role: Role: Role: Role:
                Shan-Rui Shi: Role: Role: Role:
                Chao-Nan Ma: Role: Role: Role: Role:
                Yun-Peng Lin: Role: Role:
                Wen-Gang Song: Role: Role: Role: Role:
                Shou-Dong Guo: URI : https://loop.frontiersin.org/people/666161/overviewRole: Role: Role:
                Journal
                Journal ID (nlm-ta): Front Cardiovasc Med
                Journal ID (iso-abbrev): Front Cardiovasc Med
                Journal ID (publisher-id): Front. Cardiovasc. Med.
                Title: Frontiers in Cardiovascular Medicine
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2297-055X
                Publication date (Electronic): 18 April 2024
                Publication date Collection: 2024
                Volume: 11
                Electronic Location Identifier: 1372055
                Affiliations
                [ 1 ]Department of Endocrinology and Metabolism, Guiqian International General Hospital , Guiyang, China
                [ 2 ]Institute of Lipid Metabolism and Atherosclerosis, School of Pharmacy, Shandong Second Medical University , Weifang, China
                [ 3 ]Department of General Surgery, Qixia Traditional Chinese Medicine Hospital in Shandong Province , Yantai, China
                [ 4 ]Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital , Jinan, China
                Author notes

                Edited by: Jun Yu, Temple University, United States

                Reviewed by: Chao Zhong, Jiangxi University of Chinese Medicine, China

                Munaf Hashim Zalzala, University of Baghdad, Iraq

                [* ] Correspondence: Wen-Gang Song s.com@ 123456163.com Shou-Dong Guo SD-GUO@ 123456hotmail.com
                [ † ]

                These authors have contributed equally to this work

                Article
                DOI: 10.3389/fcvm.2024.1372055
                PMC ID: 11064802
                PubMed ID: 38699583
                SO-VID: 36a538e4-641d-480d-8170-3d321e08c2bc
                Copyright © © 2024 Zhang, Zhang, Shi, Ma, Lin, Song and Guo.
                License:

                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
                Date received : 17 January 2024
                Date accepted : 09 April 2024
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 224, Pages: 0, Words: 0
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 82070469, 81770463
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article.
                This work is supported by the National Natural Science Foundation of China (82070469, 81770463, 82271803).
                Categories
                Subject: Cardiovascular Medicine
                Subject: Review
                Custom metadata
                section-at-acceptance Cardiovascular Pharmacology and Drug Discovery

                Keywords: pparα,pparβ,pparγ,lipid metabolism,inflammation,cardiovascular disease
                Data availability:
                Keywords: pparα, pparβ, pparγ, lipid metabolism, inflammation, cardiovascular disease

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