CASP3 and rheumatoid arthritis: In 2014, Chang et al. reported that Bufalin (12) (10, 20, 40 nM), the major active digoxin-like component of Chansu isolated from the skin and parotid venom glands of toad, possessed significant anti-proliferative and apoptosis inducing activities on RA-FLS; the investigators found that Bufalin can up-regulate Bax, down-regulate Bcl-2, activate Caspase -3 and PARP, increase Cyt-C release, and decrease MCMP (Δψm), and consequently the authors thought mitochondrial mediated apoptosis might be one of the possible molecular mechanisms [66].