Tendril extract of Cucurbita moschata suppresses NLRP3 inflammasome activation in murine macrophages and human trophoblast cells.

ABSTRACT

Inflammation is the root cause of many diseases that pose a serious threat to human health. Excessive inflammation can also result in preterm birth or miscarriage in pregnant women. Pumpkin (Cucurbita moschata Duchesne, CMD) is a well-known traditional health food and medicinal herb used in many countries to treat diabetes, obesity, osteoporosis, cancer and other diseases. In this study, we investigated the effects of hot water extract derived from the tendrils of C. moschata Duchesne (TCMD) on NLRP3 inflammasome activation in murine macrophages and human trophoblast cells. The TCMD treatment of LPS-primed bone marrow-derived macrophages (BMDMs) and human trophoblast cells attenuated NLRP3 inflammasome activation induced by inflammasome activators such as ATP, nigericin, and monosodium urate (MSU). TCMD treatment suppressed IL-1ß secretion in a dose-dependent manner, without affecting IL-6 secretion. In addition, TCMD inhibited NLRP3-dependent pyroptosis in BMDMs. TCMD also suppressed the release of mature IL-1ß and activation of cleaved-caspase-1 via limited ASC oligomerization. Furthermore, TCMD significantly inhibited IL-1ß secretion and pyroptotic cell death in human trophoblast cells. These results suggest that TCMD exhibits anti-inflammatory effects mediated via inhibition of NLRP3 inflammasome activation suggesting therapeutic potential against inflammatory diseases, preterm birth, and miscarriage.