title: Grape seed proanthocyanidin extract has potent anti-arthritic effects on collagen-induced arthritis by modifying the T cell balance.
abstract: Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation of the synovial joints, joint malformations, and disability. The continuous use of conventional anti-inflammatory drugs is associated with severe adverse effects. Grape seed proanthocyanidin extract (GSPE) is considered to have protective effects against several diseases. In this study based on the mouse adjuvant-induced-arthritis (AIA) model, we examined the effects of GSPE on the key mediators of arthritic inflammation, namely T cell subsets, glucocorticoid-induced tumour necrosis factor receptor (GITR) expressing cells, CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, Th17 cells, Th1/Th2 cytokines, and inflammatory mediator gene expression. We treated BALB/c mice with 25, 50, or 100 mg/kg GSPE or saline daily (14 days) per orally (p.o.) at the onset of AIA. At the peak phase of AIA (day 14), the heparinised whole blood and ankle joints of all groups were collected and tested. GSPE-treated mice showed a substantial reduction in the levels of T cell subsets, GITR-expressing cells, and Th1 cytokines as well as the inflammatory mediators (MCP-1, MIP-2, and ICAM-1) that induce them compared with the vehicle-treated (saline) and arthritic mice. However, GSPE significantly upregulated the number of Tregs and Th2 cytokine producing cell number or it also induced Th17/Treg rebalance and orchestrated various pro-inflammatory and anti-inflammatory cytokines and the gene expression of their mediators that mediate cellular infiltration into the joints. This might, contribute to its anti-arthritic activity. Our results suggest that p.o. treatment with GSPE attenuated AIA in mice might offer a promising alternative/adjunct treatment for RA.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 11451, Riyadh, Saudi Arabia. s_fayazahmad@yahoo.com
authors.forename: Sheikh Fayaz
authors.initials: SF
authors.lastname: Ahmad
authors.forename: Khairy M A
authors.initials: KM
authors.lastname: Zoheir
authors.forename: Hala E
authors.initials: HE
authors.lastname: Abdel-Hamied
authors.forename: Abdelkader E
authors.initials: AE
authors.lastname: Ashour
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Bakheet
authors.forename: Sabry M
authors.initials: SM
authors.lastname: Attia
authors.forename: Adel R A
authors.initials: AR
authors.lastname: Abd-Allah
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced* / Q000188:drug therapy / Q000382:microbiology; D003094:Collagen / Q000633:toxicity*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D056604:Grape Seed Extract / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009161:Mycobacterium; D044945:Proanthocyanidins / Q000737:chemistry / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000502:physiology
chemical_list: D016207:Cytokines; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins; D003094:Collagen
keywords: Adjuvant-induced-arthritis (AIA) model; Arthritis; Cytokines; Grape seed proanthocyanidin extract; Inflammatory mediators; T regulatory cells