4-(Hydroxymethyl)catechol Extracted From Fungi in Marine Sponges Attenuates Rheumatoid Arthritis by Inhibiting PI3K/Akt/NF-κB Signaling

Frontiers in Pharmacology

Hyukjae Choi¹  Geum J. Kim¹  Pil-Hoon Park¹  Jong Y. Lee²  Sang-Hyun Kim²  Young-Ae Choi²  Na-Hee Jeong²  Jin K. Choi³ 

[1] College of Pharmacy, Yeungnam University, Gyeongsan, South Korea;Department of Pharmacology, School of Medicine, CMRI, Kyungpook National University, Daegu, South Korea;Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, United States;

关键词: collagen-induced arthritis;    synovial fibroblasts;    4-(hydroxymethyl)catechol;    Pestalotiopsis;    matrix metalloproteinase;    inflammatory cytokine;   

DOI  :  10.3389/fphar.2018.00726

来源: DOAJ

【 摘 要 】

Rheumatoid arthritis (RA) is a progressive autoimmune disease specific to synovial joints; it causes joint damage and other systemic abnormalities, thereby leading to physical disability and early mortality. Marine sponge-derived fungi, Pestalotiopsis sp., secrete immunosuppressive compounds in the culture broth. In the present study, we isolated 4-(hydroxymethyl)catechol (4-HMC) from these fungal species, and evaluated its anti-RA effects using a murine collagen-induced arthritis model and tumor necrosis factor-α-stimulated human RA synovial fibroblasts. Oral 4-HMC administration decreased the clinical arthritis score, paw thickness, histologic and radiologic changes, and serum IgG1 and IgG2a levels. It prevented the proliferation of helper T (Th) 1/Th17 CD4+ lymphocytes isolated from inguinal lymph nodes, thereby reducing inflammatory cytokine production in CIA mice. It decreased the expression of inflammatory mediators, including cytokines and matrix metalloproteinases (MMPs), both in vitro and in vivo. We observed that 4-HMC suppresses Th immune responses and MMP expression to inhibit inflammatory cytokine production in human RA synovial fibroblasts by modulating the PI3K/Akt/NF-κB pathway. These results verify the anti-RA potential of 4-HMC.

【 授权许可】

Unknown