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Extract of Aneilema keisak inhibits transforming growth factor‐β‐dependent signalling by inducing Smad2 downregulation in keloid fibroblasts

Keloids are characterised by the excessive accumulation of extracellular matrix (ECM), especially overabundant collagen formation. In keloid fibroblasts (KFs), transforming growth factor (TGF)‐β‐dependent signalling is closely associated with a variety of keloid pathologic responses such as ECM production and fibroblast overgrowth. Thus, inhibition of TGF‐β signalling would be a potential therapeutic approach to prevent keloid scar formation. Thereby, we aimed to identify a novel TGF‐β signalling blocker among natural products using a simplified screening approach. We discovered that the extract of Aneilema keisak (A.K‐Ex) lowered TGF‐β‐dependent signalling by reducing Smad2 protein levels. Given that KFs showed altered dependency on TGF‐β for survival and proliferation, A.K‐Ex‐mediated reduction in Smad2 protein levels significantly inhibited the major characteristics of KFs such as cell growth, migration and collagen synthesis, suggesting that A.K‐Ex exhibits possible therapeutic activity on keloids.