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      Therapeutic Potential of Catechin as an IKK-β Inhibitor for the Management of Arthritis: In vitro and In vivo Approach

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          ABSTRACT

          Background:

          Rheumatoid arthritis (RA) is associated with increased levels of cytokines, for instance, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and interleukin-1 (IL-1), which exhibit potent pro-inflammatory effects and are contributing factors to disease progression. A range of cytokines, cell adhesion molecules, and enzymes that are implicated in the debilitating effects of RA are transcribed by nuclear factor kappa.

          Objectives:

          The purpose of this research was to characterize the efficacy of “catechin” as an IkappaB kinase-beta (IKK-β) inhibitor in collagen-induced arthritis (CIA) model in mice, as IKK-β is crucial in the transmission of signal-inducible NF-κβ activation.

          Methods:

          Arthritis was brought on in Bagg and Albino, but it is written BALB/c (BALB/c) male mice through subcutaneous immunization with bovine type II collagen on days 0 and 21. Catechin is given orally every day after the onset of the disease. Clinical evaluation of the prevalence and severity of the condition was done throughout the trial, and biochemical testing was done at the end (day 42).

          Results:

          In vitro findings of the study demonstrated catechin as a potent inhibitor of IKK-β with Half maximal Inhibitory Concentration (IC 50) values of 2.90 μM and 4.358 μM in IKK-β and NF-κβ transactivation activity assay, respectively. Furthermore, catechin (dose range of 10–100 mg/kg, p.o.) was effective in reducing disease incidence and clinical signs in a dose-dependent manner, with an Effective Dose for 50% of the population (ED 50) value of 79.579 mg/kg. The findings of this study demonstrate dose-dependent efficacy in terms of both disease severity (clinical scoring) and inflammatory markers (biochemical evaluation of the serum and joints).

          Conclusions:

          IKK inhibitors are a prospective target for the creation of new therapeutics for arthritis and other inflammatory diseases because it has been suggested that this enzyme is crucial in the pathophysiology of RA. The finding of this study suggests that “catechin” represents a novel inhibitor of IKK-β with promising anti-inflammatory activity.

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          Most cited references49

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          Structure, regulation and function of NF-kappa B.

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            Activators and target genes of Rel/NF-kappaB transcription factors.

            H Pahl (1999)
            The vertebrate transcription factor NF-kappaB is induced by over 150 different stimuli. Active NF-kappaB, in turn, participates in the control of transcription of over 150 target genes. Because a large variety of bacteria and viruses activate NF-kappaB and because the transcription factor regulates the expression of inflammatory cytokines, chemokines, immunoreceptors, and cell adhesion molecules, NF-kappaB has often been termed a 'central mediator of the human immune response'. This article contains a complete listing of all NF-kappaB inducers and target genes described to date. The collected data argue that NF-kappaB functions more generally as a central regulator of stress responses. In addition, NF-kappaB activation blocks apoptosis in several cell types. Coupling stress responsiveness and anti-apoptotic pathways through the use of a common transcription factor may result in increased cell survival following stress insults.
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              How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex.

              M Karin (1999)
              Rel/NF-kappaB transcription factors are primarily regulated by association with inhibitor IkappaB proteins. Thus, in most cells NF-kappaB exists in the cytoplasm in an inactive complex bound to IkappaB. Most agents that activate NF-kappaB do so through a common pathway based on phosphorylation-induced, proteasome-mediated degradation of IkappaB. The key regulatory step in this pathway involves activation of a high molecular weight IkappaB kinase (IKK) complex, whose catalysis is generally carried out by a heterodimeric kinase consisting of IKKalpha and IKKbeta subunits. This review describes the identification of proteins in the IKK complex, and the regulation and physiological functions of IKK.
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                Author and article information

                Journal
                J Pharm Bioallied Sci
                J Pharm Bioallied Sci
                JPBS
                J Pharm Bioall Sci
                Journal of Pharmacy & Bioallied Sciences
                Wolters Kluwer - Medknow (India )
                0976-4879
                0975-7406
                Oct-Dec 2023
                11 December 2023
                : 15
                : 4
                : 172-179
                Affiliations
                [1 ]Centre for Pharmaceutical Chemistry and Analysis, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, India
                [2 ]Wockhardt Research Centre, Wockhardt Pharmaceutical Pvt Ltd., Aurangabad, Maharashtra, India
                Author notes
                Address for correspondence: Dr. Viney Lather, Professor, Amity Institute of Pharmacy, Amity University, Sector - 125, Noida - 201 313, Uttar Pradesh, India. E-mail: vlather@ 123456amity.edu
                Article
                JPBS-15-172
                10.4103/jpbs.jpbs_280_23
                10790745
                38235046
                60a9dcd8-09a5-40f5-829e-09aacdbc9582
                Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 23 March 2023
                : 28 May 2023
                : 02 June 2023
                Categories
                Original Article

                Pharmacology & Pharmaceutical medicine
                anti-inflammatory,arthritis,catechin,ikk-b,nf-kb
                Pharmacology & Pharmaceutical medicine
                anti-inflammatory, arthritis, catechin, ikk-b, nf-kb

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