Antcin K inhibits VCAM-1-dependent monocyte adhesion in human rheumatoid arthritis synovial fibroblasts

David Achudhan; Sunny Li-Yun Chang; Shan-Chi Liu; Yen-You Lin; Wei-Chien Huang; Yang-Chang Wu; Chien-Chung Huang; Chun-Hao Tsai; Chih-Yuan Ko; Yueh-Hsiung Kuo; Chih-Hsin Tang

doi:10.29219/fnr.v66.8645

Antcin K inhibits VCAM-1-dependent monocyte adhesion in human rheumatoid arthritis synovial fibroblasts

Food Nutr Res. 2022 Jun 2:66. doi: 10.29219/fnr.v66.8645. eCollection 2022.

Authors

David Achudhan¹, Sunny Li-Yun Chang¹, Shan-Chi Liu², Yen-You Lin³, Wei-Chien Huang¹, Yang-Chang Wu^{1

4

5}, Chien-Chung Huang^{3

6}, Chun-Hao Tsai^{7

8}, Chih-Yuan Ko⁸, Yueh-Hsiung Kuo^{5

9

10

11}, Chih-Hsin Tang^{1

3

5

11}

Affiliations

¹ Graduate Institute of Biomedical Science, College of Medicine, China Medical University, Taichung, Taiwan.
² Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin, Taiwan.
³ School of Medicine, China Medical University, Taichung, Taiwan.
⁴ Chinese Medicine Research and Development Center, Center for Molecular Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
⁵ Department of Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan.
⁶ Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
⁷ Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan.
⁸ Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
⁹ Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
¹⁰ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
¹¹ Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.

Abstract

Background: Antcin K, an extract of Antrodia cinnamomea (a medicinal mushroom endemic to Taiwan commonly used in Chinese medicine preparations), inhibits proinflammatory cytokine production and angiogenesis in human rheumatoid arthritis synovial fibroblasts (RASFs), major players in RA disease. Antcin K also inhibits disease activity in mice with collagen-induced arthritis (CIA). Up until now, the effects of Antcin K upon cell adhesion molecules (CAMs) were unknown.

Methods: RA and healthy synovial tissue samples (n = 10 in each group) were retrieved from the Gene Expression Omnibus (GEO) database (accession code: GDS5401) to compare CAM and monocyte marker expressions. In addition, synovial tissue samples from six RA patients and six patients undergoing arthroscopy for trauma/joint derangement (healthy controls) were subjected to immunohistochemical (IHC) analysis. mRNA and protein expression levels were analyzed in RASFs using RT-qPCR (Reverse transcription-quantitative polymerase chain reaction) and Western blot. RASFs were incubated with Antcin K and examined for monocyte adherence by fluorescence microscopy. Ankle joint tissue specimens from a CIA mouse model and healthy controls were stained with hematoxylin and eosin (H&E) and Safranin-O/Fast Green to examine histological changes and evidence of bone loss. IHC analysis determined levels of vascular cell adhesion molecule 1 (VCAM-1) and CD11b in CIA ankle tissue and clinical synovial tissue.

Results: Levels of VCAM-1 expression were higher in the GEO database specimens and the study's clinical samples of RA synovial tissue compared with the healthy specimens. Antcin K dose-dependently inhibited VCAM-1 expression and monocyte adhesion in RASFs. Antcin K also significantly inhibited levels of VCAM-1 and monocyte CD11b expression in CIA tissue. These effects appeared to be mediated by MEK1/2-ERK, p38, and AP-1 signaling.

Conclusions: Antcin K seems promising for the treatment of RA and deserves further investigations.

Keywords: Antcin K; Antrodia cinnamomea; CD11b; VCAM-1; cell adhesion molecules; monocytes; rheumatoid arthritis.