Cardamonin alleviates intestinal inflammation in LPS-induced weaned piglets through the AhR/Nrf2/NLRP3 signaling pathway.

Early weaning of piglets can cause intestinal disorders and dysfunction, and may induce intestinal diseases. While cardamonin (CDN) exhibits demonstrated anti-inflammatory and antioxidant activities, its potential to alleviate intestinal barrier dysfunction and intestinal inflammation in piglets remains uninvestigated. In this research, we investigated the protective effects of CDN on the intestinal barrier function in weaned piglets and IPEC-J2 cells through activation of the AhR/Nrf2/NLRP3 pathway by establishing a lipopolysaccharide (LPS) immune stress model. Thirty piglets were assigned randomly to five groups for a duration of 15 days: basal diet group (CON), LPS challenge group (LPS), FICZ + LPS challenge group (FICZ), low-dose (3 mg/kg) CDN + LPS challenge group (LCDN) and high-dose (6 mg/kg) CDN + LPS challenge group (HCDN). From the 8th day, piglets in FICZ, LCDN, and HCDN groups were injected with FICZ or CDN once a day. On the 15th day, all piglets except the CON group were intraperitoneally injected with 100 μg/kg BW LPS, and the CON group was injected with equal amounts of saline.Our results showed that intraperitoneal administration of CDN improved LPS-induced intestinal barrier function, enhanced the intestinal antioxidant capacity, and suppressed the inflammatory response. In addition, CDN upregulated AhR expression and inhibited inflammasome activation. The in vitro experiments showed that the AhR antagonist CH223191 significantly reversed both the inhibitory effect of CDN on NLRP3 inflammasome activation and the nuclear translocation of Nrf2 mediated by CDN. Furthermore, the Nrf2 inhibitor ML385 abrogated CDN of inhibitory effects on NLRP3 inflammasome activation and the production of inflammatory cytokines. These results suggest that CDN could protect the intestinal barrier and alleviate inflammation in weaned piglets through the AhR/Nrf2/NLRP3 pathway.