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      The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

      review-article
      a , a , ** , b , a , c , d , e , f , *
      Biomedicine & Pharmacotherapy
      The Author(s). Published by Elsevier Masson SAS.
      ACE2, angiotensin converting enzyme, AMPK, AMP-activated protein kinase, APC, antigen-presenting cells, COVID-19, coronavirus disease 2019, ERK, extracellular signal-regulated kinase, HBV, hepatitis B virus, HCV, hepatitis C virus, HIV, human immunodeficiency virus, IFNγ, interferon γ, IL, interleukin, JAK, c‐Jun N‐terminal kinase, MAPK, mitogen-activated protein kinase, MERS-CoV, Middle East respiratory syndrome coronavirus, NF-κB, nuclear factor kappa B, NLR, neutrophil-lymphocyte-ratio, NO, nitric oxide, Nrf2, nuclear factor erythroid 2–related factor 2, ROS, reactive oxygen species, SARS, severe acute respiratory syndrome, SARS-CoV 2, severe acute respiratory syndrome coronavirus, STAT, signal transducer and activation of transcription, TGF-β, transforming growth factor beta, Th1, T helper 1, TLR-4, toll like receptor 4, WHO, World Health Organization, COVID-19, SARS-COV-2, Silibinin, Inflammation, Oxidative stress, Immune system, Review

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          Abstract

          The proceeding pandemic of coronavirus disease 2019 is the latest global challenge. Like most other infectious diseases, inflammation, oxidative stress, and immune system dysfunctions play a pivotal role in the pathogenesis of COVID-19. Furthermore, the quest of finding a potential pharmaceutical therapy for preventing and treating COVID-19 is still ongoing. Silymarin, a mixture of flavonolignans extracted from the milk thistle, has exhibited numerous therapeutic benefits. We reviewed the beneficial effects of silymarin on oxidative stress, inflammation, and the immune system, as primary factors involved in the pathogenesis of COVID-19. We searched PubMed/Medline, Web of Science, Scopus, and Science Direct databases up to April 2022 using the relevant keywords. In summary, the current review indicates that silymarin might exert therapeutic effects against COVID-19 by improving the antioxidant system, attenuating inflammatory response and respiratory distress, and enhancing immune system function. Silymarin can also bind to target proteins of SARS-CoV-2, including main protease, spike glycoprotein, and RNA-dependent RNA-polymerase, leading to the inhibition of viral replication. Although multiple lines of evidence suggest the possible promising impacts of silymarin in COVID-19, further clinical trials are encouraged.

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          Most cited references108

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          Clinical and immunologic features in severe and moderate Coronavirus Disease 2019

          Journal of Clinical Investigation
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            Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia

            Abstract Background In December 2019, novel coronavirus (SARS-CoV-2) pneumonia (COVID-19) was reported in Wuhan and has since rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19. Methods The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. Results Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells, and natural killer (NK) cells decreased in COVID-19 patients, and severe cases had a lower level than mild cases. The subsets showed a significant association with inflammatory status in COVID-19, especially CD8+ T cells and CD4+/CD8+ ratio. After treatment, 37 patients (67%) showed clinical response, with an increase in CD8+ T cells and B cells. No significant change in any subset was detected in nonresponsive cases. In multivariate analysis, posttreatment decrease in CD8+ T cells and B cells and increase in CD4+/CD8+ ratio were indicated as independent predictors of poor efficacy. Conclusions Peripheral lymphocyte subset alteration was associated with clinical characteristics and treatment efficacy of COVID-19. CD8+ T cells tended to be an independent predictor for COVID-19 severity and treatment efficacy.
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              The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The experience of clinical immunologists from China

              The pandemic outbreak of coronavirus disease 2019 (COVID-19) is rapidly spreading all over the world. Reports from China showed that about 20% of patients developed severe disease, resulting in a fatality of 4%. In the past two months, we clinical immunologists participated in multi-rounds of MDT (multidiscipline team) discussion on the anti-inflammation management of critical ill COVID-19 patients, with our colleagues dispatched from Chinese leading PUMC Hospital to Wuhan to admit and treat the most severe patients. Here, from the perspective of clinical immunologists, we will discuss the clinical and immunological characteristics of severe patients, and summarize the current evidence and share our experience in anti-inflammation treatment, including glucocorticoids, IL-6 antagonist, JAK inhibitors and choloroquine/hydrocholoroquine, of patients with severe COVID-19 that may have an impaired immune system.
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                Author and article information

                Journal
                Biomed Pharmacother
                Biomed Pharmacother
                Biomedicine & Pharmacotherapy
                The Author(s). Published by Elsevier Masson SAS.
                0753-3322
                1950-6007
                22 August 2022
                October 2022
                22 August 2022
                : 154
                : 113593
                Affiliations
                [a ]Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
                [b ]Department of microbiology Islamic Azad University of medical science, Tehran, Iran
                [c ]Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
                [d ]Student Research Committee, Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
                [e ]Department of Immunology, Faculty ofMedical Sciences ,Tarbiat Modares University
                [f ]Breast Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
                Author notes
                [* ]Corresponding author.
                [** ]Co-Corresponding author.
                Article
                S0753-3322(22)00982-9 113593
                10.1016/j.biopha.2022.113593
                9393179
                36027611
                a82b5f66-8135-46f7-b965-369f09b8a9b6
                © 2022 The Authors

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 9 July 2022
                : 17 August 2022
                : 19 August 2022
                Categories
                Review

                ace2, angiotensin converting enzyme,ampk, amp-activated protein kinase,apc, antigen-presenting cells,covid-19, coronavirus disease 2019,erk, extracellular signal-regulated kinase,hbv, hepatitis b virus,hcv, hepatitis c virus,hiv, human immunodeficiency virus,ifnγ, interferon γ,il, interleukin,jak, c‐jun n‐terminal kinase,mapk, mitogen-activated protein kinase,mers-cov, middle east respiratory syndrome coronavirus,nf-κb, nuclear factor kappa b,nlr, neutrophil-lymphocyte-ratio,no, nitric oxide,nrf2, nuclear factor erythroid 2–related factor 2,ros, reactive oxygen species,sars, severe acute respiratory syndrome,sars-cov 2, severe acute respiratory syndrome coronavirus,stat, signal transducer and activation of transcription,tgf-β, transforming growth factor beta,th1, t helper 1,tlr-4, toll like receptor 4,who, world health organization,covid-19,sars-cov-2,silibinin,inflammation,oxidative stress,immune system,review

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