Flavonoid quercetin-methotrexate combination inhibits inflammatory mediators and matrix metalloproteinase expression, providing protection to joints in collagen-induced arthritis

Nagaraja, Haleagrahara, Hodgson, Kelly, Miranda-Hernandez, Socorro, Hughes, Samuel, Bangra Kulur, Anupama, and Ketheesan, Natkunam (2018) Flavonoid quercetin-methotrexate combination inhibits inflammatory mediators and matrix metalloproteinase expression, providing protection to joints in collagen-induced arthritis. Inflammopharmacology, 26 (5). pp. 1219-1232.

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Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovial tissues in joints, leading to progressive destruction of cartilage and joints. The disease-modifying anti-rheumatic drugs currently in use have side-effects. Thus, there is an urgent need for safe anti-inflammatory therapies for RA. This study aimed to evaluate the therapeutic effect of the flavonoid quercetin on arthritis in mice immunized with type II collagen (CII). An arthritis model was established in C57/BL6 mice by intradermal administration of chicken CII mixed with Freund's complete adjuvant. Quercetin (30 mg/kg orally) and methotrexate (0.75 mg intraperitoneally twice a week) were administered to investigate their protective effects against collagen-induced arthritis (CIA). Levels of tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and the matrix metalloproteinases (MMP), 3, and 9 were detected to assess the anti-inflammatory effect of quercetin. The mRNA expression of MMP3, MMP9, CCL2, and TNF-α was also measured by quantitative real-time PCR. Quercetin significantly alleviated joint inflammation by reducing the levels of circulating cytokines and MMPs. There was a significant decrease in the expression of TNFα and MMP genes in the ankle joints of arthritic mice. A significant reduction in the levels of knee-joint inflammatory mediators were observed with combined quercetin and methotrexate treatment. Thus, quercetin has the potential to prevent joint inflammation and could be used as an adjunct therapy for RA patients who have an inadequate response to anti-rheumatic monotherapy.

Item ID: 54536
Item Type: Article (Research - C1)
ISSN: 1568-5608
Keywords: rheumatoid arthritis; flavonoids; inflammation; quercetin; methotrexate
Funders: Australian Institute of Tropical Health and Medicine (AITHM), Arthritis Australia (AA)
Projects and Grants: AITHM faculty research grant, AA grant 2015
Date Deposited: 13 Jul 2018 02:33
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 70%
11 MEDICAL AND HEALTH SCIENCES > 1111 Nutrition and Dietetics > 111102 Dietetics and Nutrigenomics @ 10%
11 MEDICAL AND HEALTH SCIENCES > 1115 Pharmacology and Pharmaceutical Sciences > 111502 Clinical Pharmacology and Therapeutics @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920116 Skeletal System and Disorders (incl. Arthritis) @ 100%
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