Total alkaloids from Thesium chinense inhibit lipopolysaccharide-induced respiratory inflammation by modulating Nrf2/NF-κB/NLRP3 signaling pathway

Inflammation plays a crucial role in the occurrence and development of various diseases. The whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been utilized in the management of diseases associated with inflammation in the indigenous Chinese medicine. Flavonoids were considered as the components with anti-inflammatory properties. However, any other type of chemical constituents responsible for the anti-inflammatory effect in this plant have been ignored, and not been comprehensively explored. In this study, we firstly discovered that the total alkaloids of T. chinense (BC-Alk) were potent active substances responsible for the traditional and clinical uses of T. chinense and Bairui Granules as anti-inflammatory agent. The composition of BC-Alk is identified to be quinolizidine alkaloids by UPLC-MS/MS. Moreover, the lung inflammation model in mice stimulated by LPS was adopted to test the anti-inflammatory effect of BC-Alk. The results have shown that BC-Alk significantly reduced LPS-induced lung inflammation, relieved the overproduction of IL-1β and TNF-α, and improved hyperplasia of lung tissue in mice in vivo. Mechanism studies in vitro have shown that BC-Alk activated the expression of Nrf2 and its downstream proteins NQO1 and GCLM, inhibited the phosphorylation of NF-κB, and suppressed the activation of NLRP3. Taken together, our findings suggest that BC-Alk exhibited potent inhibitory effect against lung inflammation by regulating Nrf2, NF-κB and NLRP3. Our data provided new insight for the anti-inflammatory substances of T. chinense and Bairui Granules.