Antrodia cinnamomea is a well-known medicinal mushroom in Taiwan that exhibits anti-inflammatory
biological activities. In
rheumatoid arthritis (RA), chronic
inflammation and angiogenesis driven by proinflammatory
cytokines reflect the severity of the disease. Although
biological treatments have improved the outlook for RA, no healing exists. Moreover, the available
pharmacotherapies do not work for all patients and
drug safety is a major consideration. Investigations into plant-based medicines hope to reveal better, more tolerable agents. We examined whether
Antcin K, a
phytosterol isolated from A. cinnamomea, has anti-angiogenic activity in RA. The GSE12021 gene dataset from the Gene Expression Omnibus (GEO) database was examined for levels of
vascular endothelial growth factor (
VEGF) expression in 10 RA and 10
osteoarthritis (OA) synovial tissue samples. In clinical samples,
VEGF expression was analyzed by immunohistochemical staining and ELISA in normal and RA synovial tissue, as well as OA and RA synovial fluid.
Collagen-induced arthritis (CIA) and control tissue was stained with
hematoxylin and
eosin (H&E) for histological changes;
Safranin O/
Fast Green staining examined histopathological changes and evidence of bone erosion. Human RA synovial fibroblasts (RASFs) were incubated with
Antcin K and cell viability was examined by the MTT assay.
VEGF mRNA expression was detected in RASFs using qPCR.
Antcin K significantly inhibited
VEGF expression and ameliorates endothelial progenitor cell (
EPC) migration and tube formation in RASFs by downregulating the
phospholipase C-γ/
protein kinase C-α pathway.
Antcin K also induced anti-angiogenic effects in human RASFs without cytotoxicity. PRACTICAL APPLICATIONS: Analysis of GEO dataset samples and human synovial fluids or synovial tissues revealed higher
VEGF levels in
rheumatoid arthritis (RA) samples compared with
osteoarthritis (OA) and healthy control samples.
VEGF levels were also higher in mice with
collagen-induced arthritis (CIA) than in healthy controls.
Antcin K markedly suppressed
VEGF expression in human RA synovial fibroblasts and inhibited the migration and tube formation of epithelial progenitor cells (EPCs) by downregulating the
phospholipase C-γ/
protein kinase C-α pathway. Further investigations are warranted to examine the effects of
Antcin K in other angiogenesis-associated disorders.