Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model

Rheumatoid arthritis (RA) is an autoimmune disease causing joint inflammation, deformity, cartilage deterioration, and pain. Benzimidazole derivatives exhibit various pharmacological properties. This study evaluated the antiarthritic, immunomodulatory, and anti-inflammatory potential of a benzimidaz...

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Main Authors: Ahmad Haseeb, Anjum Irfan, Usman Halima, Mobashar Aisha, Shabbir Arham, Bin Jardan Yousef A., Metouekel Amira, Dauelbait Musaab, Bourhia Mohammed
Format: Article
Language:English
Published: De Gruyter 2025-06-01
Series:Open Life Sciences
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Online Access:https://doi.org/10.1515/biol-2025-1083
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author Ahmad Haseeb
Anjum Irfan
Usman Halima
Mobashar Aisha
Shabbir Arham
Bin Jardan Yousef A.
Metouekel Amira
Dauelbait Musaab
Bourhia Mohammed
author_facet Ahmad Haseeb
Anjum Irfan
Usman Halima
Mobashar Aisha
Shabbir Arham
Bin Jardan Yousef A.
Metouekel Amira
Dauelbait Musaab
Bourhia Mohammed
author_sort Ahmad Haseeb
collection DOAJ
description Rheumatoid arthritis (RA) is an autoimmune disease causing joint inflammation, deformity, cartilage deterioration, and pain. Benzimidazole derivatives exhibit various pharmacological properties. This study evaluated the antiarthritic, immunomodulatory, and anti-inflammatory potential of a benzimidazole derivative 2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl)-N′-(4-nitrobenzylidiene) acetohydrazide (BMZ-AD) in a Freund’s complete adjuvant (FCA)-induced arthritic rat model. FCA was administered on day 0, and treatment with BMZ-AD (25 mg/kg, 50 mg/kg, and 75 mg/kg) and piroxicam (10 mg/kg) began on day 7 and continued up to 28 days. Rats were sacrificed on day 28. Arthritis was assessed using an arthritic scoring index, and paw edema was measured with a digital water plethysmometer. Biochemical and hematological parameters were analyzed, reverse transcription polymerase chain reaction measured the mRNA expression of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and molecular docking evaluated BMZ-AD interactions with these proteins. Enzyme-linked immunosorbent assay determined prostaglandin E2 levels. BMZ-AD treatment reduced inflammation, pannus formation, and pro-inflammatory cytokines (TNF-α and IL-6) and decreased PGE2 levels, comparable to piroxicam. Blood profiles improved with significant reductions in white blood cells and platelets in treatment groups. BMZ-AD demonstrated antiarthritic, anti-inflammatory, and immunomodulatory properties, suggesting that it could be a potential drug for RA treatment with fewer side effects.
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spelling doaj-art-9d26a2ec9a714b0fbf5e71ad80da704f2025-08-20T03:29:48ZengDe GruyterOpen Life Sciences2391-54122025-06-012013289510.1515/biol-2025-1083Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat modelAhmad Haseeb0Anjum Irfan1Usman Halima2Mobashar Aisha3Shabbir Arham4Bin Jardan Yousef A.5Metouekel Amira6Dauelbait Musaab7Bourhia Mohammed8Faculty of Pharmacy, The University of Lahore, Lahore, PakistanDepartment of Basic Medical Sciences, Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, PakistanDepartment of Basic Medical Sciences, Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, PakistanFaculty of Pharmacy, The University of Lahore, Lahore, PakistanDepartment of Pharmacology, Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Jail Road, Lahore, PakistanDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 11451, Riyadh, Saudi ArabiaUniversity of Technology of Compiègne, EA 4297 TIMR, 60205, Compiègne Cedex, FranceCollege of Public and Environmental Health, University of Bahr el Ghazal, Freedowm Street, Wau, 91113, South SudanLaboratory of Biotechnology and Natural Resources Valorization, Faculty of Sciences, Ibn Zohr University, 80060, Agadir, MoroccoRheumatoid arthritis (RA) is an autoimmune disease causing joint inflammation, deformity, cartilage deterioration, and pain. Benzimidazole derivatives exhibit various pharmacological properties. This study evaluated the antiarthritic, immunomodulatory, and anti-inflammatory potential of a benzimidazole derivative 2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl)-N′-(4-nitrobenzylidiene) acetohydrazide (BMZ-AD) in a Freund’s complete adjuvant (FCA)-induced arthritic rat model. FCA was administered on day 0, and treatment with BMZ-AD (25 mg/kg, 50 mg/kg, and 75 mg/kg) and piroxicam (10 mg/kg) began on day 7 and continued up to 28 days. Rats were sacrificed on day 28. Arthritis was assessed using an arthritic scoring index, and paw edema was measured with a digital water plethysmometer. Biochemical and hematological parameters were analyzed, reverse transcription polymerase chain reaction measured the mRNA expression of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and molecular docking evaluated BMZ-AD interactions with these proteins. Enzyme-linked immunosorbent assay determined prostaglandin E2 levels. BMZ-AD treatment reduced inflammation, pannus formation, and pro-inflammatory cytokines (TNF-α and IL-6) and decreased PGE2 levels, comparable to piroxicam. Blood profiles improved with significant reductions in white blood cells and platelets in treatment groups. BMZ-AD demonstrated antiarthritic, anti-inflammatory, and immunomodulatory properties, suggesting that it could be a potential drug for RA treatment with fewer side effects.https://doi.org/10.1515/biol-2025-1083rheumatoid arthritisbenzimidazole derivativeinflammationimmunomodulatorypro-inflammatory cytokines
spellingShingle Ahmad Haseeb
Anjum Irfan
Usman Halima
Mobashar Aisha
Shabbir Arham
Bin Jardan Yousef A.
Metouekel Amira
Dauelbait Musaab
Bourhia Mohammed
Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
Open Life Sciences
rheumatoid arthritis
benzimidazole derivative
inflammation
immunomodulatory
pro-inflammatory cytokines
title Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
title_full Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
title_fullStr Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
title_full_unstemmed Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
title_short Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
title_sort anti arthritic immunomodulatory and inflammatory regulation by the benzimidazole derivative bmz ad insights from an fca induced rat model
topic rheumatoid arthritis
benzimidazole derivative
inflammation
immunomodulatory
pro-inflammatory cytokines
url https://doi.org/10.1515/biol-2025-1083
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