Artemisia annua and A. afra Teas, Artemisinin, and Dihydroartemisinin Differentially Regulate ROS and Fibrosis-Associated Phenotypes in Human Dermal Fibroblasts

Fibrosis is driven by persistent fibroblast activation, oxidative stress, myofibroblast differentiation, and extracellular matrix remodeling, yet available antifibrotic therapies remain limited. This study evaluated whether artemisinin (ART), dihydroartemisinin (DHA), and traditional tea infusions of Artemisia annua and A. afra differentially regulate fibrosis-associated responses in human dermal fibroblasts. Neonatal and adult human dermal fibroblasts were cultured under pre-fibrotic or TGF-β/ascorbic acid-stimulated pro-fibrotic conditions and assessed for intracellular ROS, scratch-wound closure, collagen gel contraction, fibrosis-associated gene expression, and α-SMA protein abundance. Artemisia teas produced greater ROS reduction than purified ART or DHA, with A. afra showing the strongest antioxidant effect despite lacking detectable artemisinin. DHA and A. annua most consistently suppressed scratch closure, while A. afra produced intermediate inhibition and ART was comparable to vehicle control. Collagen gel contraction was most strongly reduced by A. annua, with DHA and A. afra producing intermediate suppression. Under pro-fibrotic conditions, DHA and A. annua downregulated ACTA2, A. annua suppressed COL1A1, and DHA and A. annua increased matrix-remodeling MMP expression. Reduced levels of α-SMA confirmed the antifibrotic effects. These findings indicate that antifibrotic activity differs among artemisinin-related compounds and whole-plant Artemisia preparations, with DHA and A. annua showing the strongest overall activity.