Phytoconstituents of Red Grape Seeds Extract as Inflammatory Modulator in Adjuvant Arthritic Rats: Role Of IL-1 and its Receptor Blocking

Abstract This study focused on investigating the phytochemical composition of the total extract and the ethyl acetate fraction of red grape (Vitis vinifera L.) seeds as well as evaluating the total extract as anti-arthritis agents in rats compering with the new treating agent; interleukin-1 receptor antagonist (IL-1RA) and the classical anti-inflammatory drug; indomethacin. HPLC and LC-ESI-MS analysis was applied for identification and quantification the flavonoid and phenolic compounds. Arthritis was induced by using complete Freund’s adjuvant (CFA). The percentages of edema as well as the arthritis index were evaluated on the 7th, 14th, 21th and 28th day post CFA-induction. The evaluation was done by measuring serum interleukin-1 beta (IL-1β), IL-1 receptor type I gene expression, oxidative stress markers, intracellular adhesion molecule-1 (ICAM-1), caspase-3 (cas-3), c-reactive protein (CRP), prostaglandin E2 (PGE2), total protein content, DNA fragmentation, chromosomal aberration and cytogenic damage. The histopathological features of the ankle joint were analyzed. Stilbenes, phenolic acids, and anthocyanins were the major identified classes in the ethyl acetate fraction, while flavan-3-ol, oligomeric and polymeric procyanidins, flavonoid glucosides and phenolic acids were the main categories in the total extract. Three major proanthocyanidin compounds; gallic-4-O-β-glucopyranoside, catechin 3,5-di-O-gallate and catechin 3-O-gallate were identified in the ethyl acetate fraction. Treatment with seeds extract and IL-1RA improved the selected parameters by variable degrees. IL-1 RA showed a pronounced treating effect. In conclusion, Vitis vinifera seeds extract and IL-1RA are considered as promising anti-arthritis agents. More studies are required to conduct Vitis vinifera seeds extract and IL-1RA in pharmacological and clinical applications. GRAPHICAL ABSTRACT