Inhibitory effects of mixed flavonoid supplements on unraveled DSS-induced ulcerative colitis and arthritis

Introduction: The mixed flavonoid supplement (MFS) [Trimethoxy Flavones (TMF) + epigallocatechin-3-gallate (EGCG)] can be used to suppress inflammatory ulcers as an ethical medicine in Ayurveda. The inflammation of the rectum and anal regions is mostly attributed to nuclear factor kappa beta (NF-κB)...

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Main Authors: Siva Prasad Panda, Mahamat Sami Adam Mahamat, Malikyahia Abdul Rasool, DSNBK Prasanth, Idris Adam Ismail, Moyed Abasher Ahmed Abasher, Bikash Ranjan Jena
Format: Article
Language:English
Published: Tabriz University of Medical Sciences 2023-01-01
Series:BioImpacts
Subjects:
Online Access:https://bi.tbzmed.ac.ir/PDF/bi-13-73.pdf
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author Siva Prasad Panda
Mahamat Sami Adam Mahamat
Malikyahia Abdul Rasool
DSNBK Prasanth
Idris Adam Ismail
Moyed Abasher Ahmed Abasher
Bikash Ranjan Jena
author_facet Siva Prasad Panda
Mahamat Sami Adam Mahamat
Malikyahia Abdul Rasool
DSNBK Prasanth
Idris Adam Ismail
Moyed Abasher Ahmed Abasher
Bikash Ranjan Jena
author_sort Siva Prasad Panda
collection DOAJ
description Introduction: The mixed flavonoid supplement (MFS) [Trimethoxy Flavones (TMF) + epigallocatechin-3-gallate (EGCG)] can be used to suppress inflammatory ulcers as an ethical medicine in Ayurveda. The inflammation of the rectum and anal regions is mostly attributed to nuclear factor kappa beta (NF-κB) signaling. NF-κB stimulates the expression of matrix metalloproteinase (MMP9), inflammatory cytokines tumor necrosis factor (TNF-α), and interleukin-1β (IL-1β). Although much research targeted the NF-κB and MMP9 signaling pathways, a subsequent investigation of target mediators in the inflammatory ulcer healing and NF-κB pathway has not been done. Methods: The docking studies of compounds TMF and EGCG were performed by applying PyRx and available software to understand ligand binding properties with the target proteins. The synergistic ulcer healing and anti-arthritic effects of MFS were elucidated using dextran sulfate sodium (DSS)-induced colon ulcer in Swiss albino rats. The colon mucosal injury was analyzed by colon ulcer index (CUI) and anorectic tissue microscopy. The IL-1β, tumor necrosis factor (TNF-α), and the pERK, MMP9, and NF-κB expressions in the colon tissue were determined by ELISA and Western blotting. RT-PCR determined the mRNA expression for inflammatory marker enzymes. Results: The docking studies revealed that EGCG and TMF had a good binding affinity with MMP9 (i.e., -6.8 and -6.0 Kcal/mol) and NF-kB (-9.4 and 8.3 kcal/mol). The high dose MFS better suppressed ulcerative colitis (UC) and associated arthritis with marked low-density pERK, MMP9, and NF-κB proteins. The CUI score and inflammatory mediator levels were suppressed with endogenous antioxidant levels in MFS treated rats. Conclusion: The MFS effectively unraveled anorectic tissue inflammation and associated arthritis by suppressing NF-κB-mediated MMP9 and cytokines.
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spelling doaj.art-534aad33e05c4e94b991bf44db4e19e92023-04-16T06:57:48ZengTabriz University of Medical SciencesBioImpacts2228-56602228-56522023-01-01131738410.34172/bi.2022.23523bi-23523Inhibitory effects of mixed flavonoid supplements on unraveled DSS-induced ulcerative colitis and arthritisSiva Prasad Panda0Mahamat Sami Adam Mahamat1Malikyahia Abdul Rasool2DSNBK Prasanth3Idris Adam Ismail4Moyed Abasher Ahmed Abasher5Bikash Ranjan Jena6Pharmacology Research Division, Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, IndiaPharmacognosy Research Division, College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur, IndiaPharmacognosy Research Division, College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur, IndiaDepartment of Pharmacognosy, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada, AP, IndiaPharmacognosy Research Division, College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur, IndiaPharmacognosy Research Division, College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur, IndiaSIIMS College of Pharmacy, Guntur, IndiaIntroduction: The mixed flavonoid supplement (MFS) [Trimethoxy Flavones (TMF) + epigallocatechin-3-gallate (EGCG)] can be used to suppress inflammatory ulcers as an ethical medicine in Ayurveda. The inflammation of the rectum and anal regions is mostly attributed to nuclear factor kappa beta (NF-κB) signaling. NF-κB stimulates the expression of matrix metalloproteinase (MMP9), inflammatory cytokines tumor necrosis factor (TNF-α), and interleukin-1β (IL-1β). Although much research targeted the NF-κB and MMP9 signaling pathways, a subsequent investigation of target mediators in the inflammatory ulcer healing and NF-κB pathway has not been done. Methods: The docking studies of compounds TMF and EGCG were performed by applying PyRx and available software to understand ligand binding properties with the target proteins. The synergistic ulcer healing and anti-arthritic effects of MFS were elucidated using dextran sulfate sodium (DSS)-induced colon ulcer in Swiss albino rats. The colon mucosal injury was analyzed by colon ulcer index (CUI) and anorectic tissue microscopy. The IL-1β, tumor necrosis factor (TNF-α), and the pERK, MMP9, and NF-κB expressions in the colon tissue were determined by ELISA and Western blotting. RT-PCR determined the mRNA expression for inflammatory marker enzymes. Results: The docking studies revealed that EGCG and TMF had a good binding affinity with MMP9 (i.e., -6.8 and -6.0 Kcal/mol) and NF-kB (-9.4 and 8.3 kcal/mol). The high dose MFS better suppressed ulcerative colitis (UC) and associated arthritis with marked low-density pERK, MMP9, and NF-κB proteins. The CUI score and inflammatory mediator levels were suppressed with endogenous antioxidant levels in MFS treated rats. Conclusion: The MFS effectively unraveled anorectic tissue inflammation and associated arthritis by suppressing NF-κB-mediated MMP9 and cytokines.https://bi.tbzmed.ac.ir/PDF/bi-13-73.pdfmfsanorectic ulcerarthritisnf-κbmmp9cytokines
spellingShingle Siva Prasad Panda
Mahamat Sami Adam Mahamat
Malikyahia Abdul Rasool
DSNBK Prasanth
Idris Adam Ismail
Moyed Abasher Ahmed Abasher
Bikash Ranjan Jena
Inhibitory effects of mixed flavonoid supplements on unraveled DSS-induced ulcerative colitis and arthritis
BioImpacts
mfs
anorectic ulcer
arthritis
nf-κb
mmp9
cytokines
title Inhibitory effects of mixed flavonoid supplements on unraveled DSS-induced ulcerative colitis and arthritis
title_full Inhibitory effects of mixed flavonoid supplements on unraveled DSS-induced ulcerative colitis and arthritis
title_fullStr Inhibitory effects of mixed flavonoid supplements on unraveled DSS-induced ulcerative colitis and arthritis
title_full_unstemmed Inhibitory effects of mixed flavonoid supplements on unraveled DSS-induced ulcerative colitis and arthritis
title_short Inhibitory effects of mixed flavonoid supplements on unraveled DSS-induced ulcerative colitis and arthritis
title_sort inhibitory effects of mixed flavonoid supplements on unraveled dss induced ulcerative colitis and arthritis
topic mfs
anorectic ulcer
arthritis
nf-κb
mmp9
cytokines
url https://bi.tbzmed.ac.ir/PDF/bi-13-73.pdf
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