The antagonism of 6-shogaol in high-glucose-activated NLRP3 inflammasome and consequent calcification of human artery smooth muscle cells

• Main Authors: Te-Chuan Chen, Chia-Kung Yen, Ying-Chen Lu, Chung-Sheng Shi, Rong-Ze Hsieh, Shun-Fu Chang, Cheng-Nan Chen
• Format: Article
• Language: English
• Published: BMC 2020-01-01
• Series: Cell & Bioscience
• Subjects: 6-Shogaol; Interleukin-1β; NLRP3 Inflammasome; Vascular calcification; Smooth muscle cells
• Online Access: https://doi.org/10.1186/s13578-019-0372-1

Abstract Background Vascular calcification is the major reason for high mortality of cardiovascular complications for diabetes. Interleukin (IL)-1β has been implicated in this pathogenesis, but its precise role and clinical evidence have not been clearly identified. Hence, this study was aimed to investigate whether high concentration of glucose (HG), which mimics the hyperglycemia environment, could initiate vascular calcification through NLRP3/IL-1β inflammasome and the underlying mechanism. Recently, 6-shogaol, a major ginger derivate, has been elucidated its pharmaceutic role for various diseases. Therefore, the aims of this study also determined 6-shogaol effect in vascular calcification of HG initiation. Result Human artery smooth muscle cells (HASMCs) were used in this study. Glucose concentrations at 5 and 25 mM were defined as normal and HG status, respectively. The results showed that HG could increase the NLRP3, cleaved caspase 1, and pro/mature IL-1β levels to induce the expressions of bone-related matrix proteins and subsequent HASMC calcification. This process was regulated by Akt activation and reactive oxygen species (ROS) production. Moreover, 6-shogaol could inhibit the Akt/ROS signaling and NLRP3/caspase 1/IL-1β inflammasome and hence attenuated HASMC calcification. Conclusions This study elucidates the detailed mechanism of HG-initiated HASMC calcification through NLRP3/caspase 1/IL-1β inflammasome and indicates a potential therapeutic role of 6-shogaol in vascular calcification complication of diabetes.