Cafestol and kahweol are natural diterpenes extracted from coffee beans. In addition to the effect of raising serum lipid, in vitro and in vivo experimental results have revealed that the two diterpenes demonstrate multiple potential pharmacological actions such as anti-inflammation, hepatoprotective, anti-cancer, anti-diabetic, and anti-osteoclastogenesis activities. The most relevant mechanisms involved are down-regulating inflammation mediators, increasing glutathione (GSH), inducing apoptosis of tumor cells and anti-angiogenesis. Cafestol and kahweol show similar biological activities but not exactly the same, which might due to the presence of one conjugated double bond on the furan ring of the latter. This review aims to summarize the pharmacological properties and the underlying mechanisms of cafestol-type diterpenoids, which show their potential as functional food and multi-target alternative medicine.

Injury-induced fibroblast-to-myofibroblast differentiation is a key event of renal fibrosis. YAP, a transcriptional coactivator, plays an important role in fibroblast activation and Smad transcriptional activity to promote TGF-β-induced differentiation from fibroblasts to myofibrolasts. MST1/2, a negative regulator of YAP, also increases in fibroblasts by TGF-β stimulation. Here we examined whether MST1/2, as a negative regulator, attenuated YAP and TGF-β/Smad signaling in fibroblasts to reduce fibrosis. The MST1/2 and YAP expression levels increased in PDGFRα+ cells of obstructed kidneys following the increase of TGF-β and renal fibrosis after UUO. The PDGFRα+ cells-specific knockout of Mst1/2 in mice increased UUO-induced myofibroblast accumulation and fibrosis. In cultured fibroblasts, TGF-β increased YAP and promoted its nucleus entry, but a high dose and prolonged treatment of TGF-β increased the MST1/2 activation to prevent YAP from entering the nucleus. Our results indicated that MST1/2 is a negative-feedback signal of TGF-β-induced fibroblast differentiation.