Fangchinoline from traditional Chinese medicine targets T cells in Sjögren’s syndrome, inducing apoptosis via oxidative stress and Akt inhibition

In a breakthrough study published in Current Molecular Pharmacology, researchers from Tongji University have uncovered how Fangchinoline (Fan), a bioactive alkaloid from the traditional Chinese herb Stephania tetrandra, combats T cell-mediated damage in Sjögren’s syndrome (SS). By analyzing SS salivary gland datasets, the team confirmed T cells’ pivotal role in SS pathology, prompting investigations into Fan’s effects on Jurkat T cells, a model for CD4+ T cells.

Fan exhibited potent anti-proliferative effects, with an IC50 of 2.49 μM, and induced dose-dependent apoptosis. "Fan not only elevated reactive oxygen species (ROS) but also caused DNA damage, a double strike against T cell survival," explained lead author Yubo Xu. ROS scavenger N-acetylcysteine (NAC) reversed Fan’s apoptotic effects, confirming oxidative stress as a key mechanism.

Crucially, Fan suppressed the pro-survival Akt pathway, impairing DNA repair. When combined with H₂O₂-induced oxidative stress, Akt inhibition exacerbated DNA damage and apoptosis. "This dual action—ROS induction and Akt blockade—makes Fan a promising candidate for SS therapy," Xu noted.

The study builds on Fan’s historical use in rheumatism and aligns with prior findings of its efficacy in SS mouse models. Future research will explore Fan’s broader applications in autoimmune diseases.