生物活性

• 描述Aspartic proteinases are a class of enzymes commonly expressed in osteoclasts that contribute to bone resorption in endosome/lysosome system. Pepstatin A is a chemotactic pentapeptide that inhibits different kinds of aspartic proteinases, such as pepsin, cathepsins D and E. In a co-culture system, Pepstatin A at 15 - 120 μM suppressed the formation of TRAP-positive multinuclear cells in a dose-dependent manner. Pepstatin A at the same concentration range also exhibited a similar inhibitory effect on RANKL/M-CSF-induced osteoclastogenesis in bone marrow culture. In bone marrow cells separated from stromal cells on a Sephadex G-10 column, pepstatin A at 15 - 120 μM dose-dependently suppressed RANKL-induced osteoclastogenesis. In osteoclasts generated from bone marrow cells and stimulated with RANKL and M-CSF, pepstatin A at 120 μM strongly inhibited the early stage of osteoclast formation. Pepstatin A at 15 μM sufficiently inhibited the aspartic proteinase activity in bone marrow cells and the complete inhibition was seen at the concentration of 90 μM. Additionally, pretreatment of pepstatin A for 3 hours inhibited RANKL-induced ERK activation and NFATc1 expression in osteoclasts. Pepstatin A stimulated human neutrophil degranulation and superoxide production with EC₅₀ values of 0.75 μM and 1.5 μM respectively.

• 动物研究
  剂量	Mice: 25 mg/kg - 200 mg/kg[3] (i.p.)
  给药途径	i.p.