Hyaluronic acid-green tea catechin conjugates as a potential therapeutic agent for rheumatoid arthritis

• Published in: RSC advances Vol. 11; no. 24; pp. 14285 - 14294
• Main Authors: Lee, Fan, Bae, Ki Hyun, Ng, Shengyong, Yamashita, Atsushi, Kurisawa, Motoichi
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 19.04.2021; The Royal Society of Chemistry
• Subjects: animal models; Arthritis; Catechin; cell specificity; Chemical compounds; Chemistry; Conjugates; Edema; epigallocatechin gallate; Fibroblasts; Fluorescence; Green tea; histopathology; Hyaluronic acid; Infrared imaging; interleukin-6; Interleukins; Pathogenesis; Pharmacology; Rheumatoid arthritis; secretion; Tea; therapeutics
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d1ra01491a

Fibroblast-like synoviocytes are a key effector cell type involved in the pathogenesis of rheumatoid arthritis. The major green tea catechin, epigallocatechin-3- O -gallate (EGCG), has attracted significant interest for rheumatoid arthritis therapy because of its ability to suppress the proliferation and interleukin-6 secretion of synoviocytes. However, therapeutic efficacy of EGCG has been limited by a lack of target cell specificity. Herein we report hyaluronic acid-EGCG (HA-EGCG) conjugates as an anti-arthritic agent that is capable of targeting fibroblast-like synoviocytes via HA-CD44 interactions. These conjugates exhibited superior anti-proliferative and anti-inflammatory activities compared with EGCG under simulated physiological conditions. Near-infrared fluorescence imaging revealed preferential accumulation of the conjugates at inflamed joints in a collagen-induced arthritis rat model, and their anti-arthritic efficacy was investigated by measuring a change in the edema and histopathological scores. Our findings suggest the potential of HA-EGCG conjugates as an anti-arthritic agent for the treatment of rheumatoid arthritis. Macromolecular HA-EGCG conjugates undergo targeted internalization by CD44-overexpressing fibroblast-like synoviocytes and subsequently cause H 2 O 2 -induced cell death and inhibition of IL-6 secretion, thereby suppressing the progression of arthritis.