{"title":"Mitigation of inflammation and oxidative stress in FCA-induced arthritic rat model through gum acacia intervention: a comprehensive in‑vivo study.","authors":"Sobia Khalid Awan, Ali Sharif, Bushra Akhtar","doi":"10.1007/s10787-025-01907-7","DOIUrl":null,"url":null,"abstract":"<p><p>Rheumatoid arthritis is a persistent immune-mediated inflammatory disorder that primarily affects joint bones, impacting approximately 0.5-1.0% of the global population. People with RA are 1.5 times more likely to develop cardiovascular conditions, including atherosclerosis. This study explored the therapeutic potential of GAc in a rat model of RA induced by CFA, focusing on its impact on biomarkers associated with atherosclerosis. Molecular docking studies indicated strong binding affinities of GAc with key inflammatory cytokines, including TNF-α, IL-6, IL-1β, NF-κB and PRMT-1. The experimental model of 23 days involved the induction of arthritis by injecting 0.15 mL of CFA into the sub-plantar region of the rats' left hind paws. GAc was dissolved in distilled water and administered to rats via oral gavage. Our results revealed that the administration of GAc, particularly in combination with MtxSt (GAc 10 g/kg + MtxSt), significantly (p < 0.001) reduced arthritic scores, joint stiffness scores, paw thickness, levels of lipids (LDL, VLDL, TG, and TC), asymmetric dimethylarginine (ADMA), homocysteine, oxidative stress, and pro-inflammatory cytokines. In addition, GAc markedly (p < 0.001) improved body weight, hematological parameters (RBC, %HCT and Hb), HDL, dimethylarginine dimethylaminohydrolase-1(DDAH-1), and CST levels. Histopathological assessments showed that GAc 10 g/kg + MtxSt significantly alleviated bone and cartilage erosion (p < 0.001), pannus formation (p < 0.001), synovial hyperplasia (p < 0.01), vascular congestion (p < 0.001) and inflammatory cell infiltration (p < 0.001). The therapeutic efficacy of GAc is ascribed to its anti-inflammatory, antioxidant, and anti-atherosclerotic properties. This study suggested that combining GAc with MtxSt exerts a synergistic effect in mitigating inflammation and reducing the risk of atherosclerosis associated with RA.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"5365-5385"},"PeriodicalIF":5.3000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Inflammopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10787-025-01907-7","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/13 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Rheumatoid arthritis is a persistent immune-mediated inflammatory disorder that primarily affects joint bones, impacting approximately 0.5-1.0% of the global population. People with RA are 1.5 times more likely to develop cardiovascular conditions, including atherosclerosis. This study explored the therapeutic potential of GAc in a rat model of RA induced by CFA, focusing on its impact on biomarkers associated with atherosclerosis. Molecular docking studies indicated strong binding affinities of GAc with key inflammatory cytokines, including TNF-α, IL-6, IL-1β, NF-κB and PRMT-1. The experimental model of 23 days involved the induction of arthritis by injecting 0.15 mL of CFA into the sub-plantar region of the rats' left hind paws. GAc was dissolved in distilled water and administered to rats via oral gavage. Our results revealed that the administration of GAc, particularly in combination with MtxSt (GAc 10 g/kg + MtxSt), significantly (p < 0.001) reduced arthritic scores, joint stiffness scores, paw thickness, levels of lipids (LDL, VLDL, TG, and TC), asymmetric dimethylarginine (ADMA), homocysteine, oxidative stress, and pro-inflammatory cytokines. In addition, GAc markedly (p < 0.001) improved body weight, hematological parameters (RBC, %HCT and Hb), HDL, dimethylarginine dimethylaminohydrolase-1(DDAH-1), and CST levels. Histopathological assessments showed that GAc 10 g/kg + MtxSt significantly alleviated bone and cartilage erosion (p < 0.001), pannus formation (p < 0.001), synovial hyperplasia (p < 0.01), vascular congestion (p < 0.001) and inflammatory cell infiltration (p < 0.001). The therapeutic efficacy of GAc is ascribed to its anti-inflammatory, antioxidant, and anti-atherosclerotic properties. This study suggested that combining GAc with MtxSt exerts a synergistic effect in mitigating inflammation and reducing the risk of atherosclerosis associated with RA.
期刊介绍:
Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas:
-Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states
-Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs
-Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents
-Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain
-Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs
-Muscle-immune interactions during inflammation [...]