Effect of mulberrin on inhibiting the activation of NLRP3 inflammasome and relieving infectious shock

ObjectiveTo investigate the effect of mulberrin, a Chinese herbal extract, on NLRP3 inflammasome activation, and provide new insight for NLRP3-related disease.

MethodsWestern blotting and ELISA were used to detect the expression level of caspase-1 and interleukin-1β of mouse bone marrow derived macrophages (BMDM) and human THP-1 cells induced by three agonists: Nigerian bacteriocin, monosodium urate and adenosine triphosphate (ATP).Mouse septic shock model induced by lipopolysaccharide (LPS) was constructed, and experimental mice were divided into placebo group, septic shock group and mulberrin treatment group.The levels of IL-1β and TNF-α in intraperitoneal lavage fluid and serum were detected by ELISA.

ResultsIn vitro experiments, we found that the processing and maturation of caspase-1 and IL-1β induced by three classic inflammasome agonists (Nigericin, MSU and ATP) were inhibited by mulberrin in BMDM and THP-1 cells (P < 0.01).However, there was no obviously difference observed on the secretion of non-inflammasome-related cytokines, such as TNF-α (P>0.05).In vivo experiments, mulberrin treatment alleviated septic shock, significantly inhibited IL-1β expression in serum and intraperitoneal lavage fluid of mice, and prolonged the survival time of LPS-induced mice(P < 0.01).

ConclusionsAs an active ingredient of Chinese herb extract, mulberrin can inhibit the NLRP3 inflammasome activation in vitro and in vivo.Our study provide experimental evidences for the treatment of NLRP3-related diseases.