Novel diterpenoid glycosides from Rubus chingii Hu induce apoptosis in BPH-1 cells through fas/caspase-8 pathway activation.

Rubus chingii Hu, a food material with medicinal value, has been used to treat urinary system diseases, such as prostatitis, benign prostate hyperplasia (BPH) and lower urinary tract symptoms (LUTS). However, there is no research on the efficacy and mechanism of compounds of R. chingii. in treating BPH. In this study, 10 previously unreported ent-pimarane-type (rubuschinoside A-B, 1-2), ent-isopimarane-type (rubuschinoside CD, 3-4) and ent-labdane-type (goshonoside J16-21, 5-10) diterpene glycosides were isolated from the dried fruits of R. chingii. Their structures were elucidated and confirmed using high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance spectroscopy (NMR), single crystal X-ray diffraction and electron capture detector (ECD). All compounds were tested for their apoptosis-inducing activity in BPH cells, and compounds 1, 3, 4 and 8 exhibited significant pro-apoptotic effects. Further apoptosis mechanistic studies on compound 8 revealed that it could increase the expression of Fas, FADD, caspase 3 and caspase 8 mRNA expression levels at 50 μM. Collectively, this study suggested that diterpenoid glycosides from R. Chingii may induce apoptosis in hyperplastic prostate cells through activation of the Fas/caspase-8 signaling cascade.