ReferenceID 2990

Tomatidine Suppresses the Destructive Behaviors of Fibroblast-Like Synoviocytes and Ameliorates Type II Collagen-Induced Arthritis in Rats

Front Pharmacol

Fibroblast-like synoviocytes (FLSs) are the prominent non-immune cells in synovium and play a pivotal role in rheumatoid arthritis (RA) pathogenesis. Searching for natural compounds that may suppress the pathological phe

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Reference Id
2990
Evidence Id
19580
Core Evidence Id
19580
Source Reference Id
5984
Herb2 Reference Id
HBREF006781
Subject Paper Key
HBIN046526_34512321
Pubmed Id
34512321
Doi
10.3389/fphar.2021.670707
Paper Title
Tomatidine Suppresses the Destructive Behaviors of Fibroblast-Like Synoviocytes and Ameliorates Type II Collagen-Induced Arthritis in Rats
Paper Abstract
Fibroblast-like synoviocytes (FLSs) are the prominent non-immune cells in synovium and play a pivotal role in rheumatoid arthritis (RA) pathogenesis. Searching for natural compounds that may suppress the pathological phenotypes of FLSs is important for the development of RA treatment. Tomatidine (Td), a steroidal alkaloid derived from the solanaceae family, has been reported to have anti-inflammatory, anti-tumor and immunomodulatory effects. However, its effect on RA remains unknown. Here, we examined the inhibitory effect of Td on TNFalpha-induced arthritic FLSs, and subsequently investigated its therapeutic effect on collagen-induced arthritis (CIA) rats. Our results revealed that Td significantly inhibited TNFalpha-induced proliferation and migration of arthritic FLSs. In addition, we found that Td treatment could efficaciously ameliorate synovial inflammation and joint destruction of rats with CIA. Both in vitro and in vivo studies showed that Td significantly suppressed the production of pro-inflammatory cytokines including IL-1beta, IL-6 and TNFalpha, and downregulated the expression of MMP-9 and RANKL. Further molecular mechanism studies revealed that the inhibitory effect of Td on RA might attribute to the decreased activations of MAPKs (ERK and JNK) and NF-kappaB. These findings provide evidence that Td has the potential to be developed into a complementary or alternative agent for RA therapy.
Journal
Front Pharmacol
Publish Year
2021
Experiment Subject
rat; tnfalpha-induced arthritic flss
Experiment Type
Animal & Cell Experiment
Phenotype Related
Rheumatoid Arthritis; Synovial Inflammation; Collagen-induced Arthritis
Paper Title Cn
Paper Title En
Tomatidine Suppresses the Destructive Behaviors of Fibroblast-Like Synoviocytes and Ameliorates Type II Collagen-Induced Arthritis in Rats
Bilingual Status
semi_complete