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

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.

Therapeutic potential of ginger against COVID-19: Is there enough evidence?

“…142 In vitro experiments have revealed that high concentrations of glucose initiate the calcification in human vascular smooth muscle cells via upregulating the NLRP3 inflammasome-IL-1β axis. 143 6-shogaol reduces the calcification through attenuating the ROS production and downregulating the NLRP3 inflammasome. 143 The ginger-derived exosome-like nanoparticles (ELNs) also inhibit the NLRP3 inflammasome assembling, IL-1β, and IL-18 production as well as pyroptosis in the mouse macrophages.…”

“… 143 6-shogaol reduces the calcification through attenuating the ROS production and downregulating the NLRP3 inflammasome. 143 The ginger-derived exosome-like nanoparticles (ELNs) also inhibit the NLRP3 inflammasome assembling, IL-1β, and IL-18 production as well as pyroptosis in the mouse macrophages. 144 The ELN-related suppressive activity was largely attributed to its lipid fraction.…”

A New Method for Screening Natural Products to Stimulate IFN-γ Production in Jurkat Human T Lymphocytes

“…43,44 Evidence shows that 6-shogaol can inhibit breast cancer cell invasion and exhibit an antagonistic effect in high-glucoseinduced NKRP3 inflammasomes in artery smooth muscle cells. 45,46 Although both hits were not novel chemicals, and their immunomodulatory role as well as their capacities to induce the expression of IFN-g have been extensively studied, it was still fortunate for us to detect them, which might help to validate the effectiveness of our screening model. In order to find novel potent chemicals, we need to expand the screening scale, but as least our primary screening data had encouraged us to continue the screening work.…”

6-shogaol suppresses oxidative damage in L6 muscle cells

“…6-shogaol has been reported to have higher radical scavenging effect and anti-inflammatory effect than gingerol [22]. In addition, 6-shogaol acutely relaxes airway smooth muscle and attenuates human artery smooth muscle cells calcification [23,24]. It has been reported that treatment of ginger extracts resulted in improvement of cellular differentiation of myoblast by cell cycle regulation [25].…”