2. Academic Validation
  3. 8-Shogaol inhibits rheumatoid arthritis through targeting TAK1

8-Shogaol inhibits rheumatoid arthritis through targeting TAK1

  • Pharmacol Res. 2022 Apr:178:106176. doi: 10.1016/j.phrs.2022.106176.
Seongin Jo 1,  Snigdha Samarpita 2,  Ji Su Lee 1,  Yong Joon Lee 1,  Joe Eun Son 3,  Minju Jeong 4,  Jae Hwan Kim 1,  Seungpyo Hong 5,  Seung-Ah Yoo 6,  Wan-Uk Kim 7,  Mahaboobkhan Rasool 8,  Sanguine Byun 9
Affiliations

Affiliations

  • 1 Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
  • 2 Immunopathology Lab, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore 632 014, Tamil Nadu, India.
  • 3 Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
  • 4 Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.
  • 5 Food Functionality Research Division, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of Korea.
  • 6 Department of biomedicine and health sciences, The Catholic University of Korea, Seoul 06591, Republic of Korea.
  • 7 Division of Rheumatology, Department of Internal Medicine, Catholic University of Korea, Seoul 06591, Republic of Korea.
  • 8 Immunopathology Lab, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore 632 014, Tamil Nadu, India. Electronic address: mkr474@gmail.com.
  • 9 Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea. Electronic address: sanguine@yonsei.ac.kr.
PMID: 35283302 DOI: 10.1016/j.phrs.2022.106176
Abstract

Rheumatoid arthritis (RA) is a chronic immune-mediated disorder, mainly characterized by synovial inflammation and joint damage. If insufficiently treated, RA can lead to irreversible joint destruction and decreased life expectancy. While better understanding of the pathologies and the development of new antirheumatic drugs have improved the outcome of individuals with RA, many patients still cannot achieve remission and experience progressive disability. Fibroblast-like synoviocytes (FLS) have gained attention due to its pivotal role in RA pathogenesis and thus targeting FLS has been suggested as an attractive therapeutic strategy. To identify candidate molecules with strong inhibitory activity against FLS inflammation, we tested the effect of 315 natural extracts against IL-17-mediated IL-6 production. Zingiber officinale was found as the top hit and further analysis on the active compound responsible led to the discovery of 8-shogaol as a potent molecule against synovitis. 8-Shogaol displayed significant inhibitory effects against TNF-α-, IL-1β-, and IL-17-mediated inflammation and migration in RA patient-derived FLS (RA-FLS) and 3D synovial culture system. 8-Shogaol selectively and directly inhibited TAK1 activity and subsequently suppressed IKK, Akt, and MAPK signaling pathways. Moreover, treatment with 8-shogaol reduced paw thickness and improved walking performance in the adjuvant-induced arthritic (AIA) rat model. 8-Shogaol also reversed pathologies of joint structure in AIA rats and decreased inflammatory biomarkers in the joints. Collectively, we report a novel natural compound that inhibits RA through reversing pathologies of the inflamed synovium via targeting TAK1.

Keywords

8-shogaol; Fibroblast-like synoviocytes; Rheumatoid arthritis; TAK1.

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