Hu Xiwen, Fang Yi, Zhang Yalei, Deng Tanjie, Ji Mengyao, Yang Wen, Shi Liguang, Xun Wenjuan
Institute of Tropical Agriculture and Forestry, Hainan University, Haikou 570228, China.
Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571100, China.
Int Immunopharmacol. 2025 Jul 4;162:115144. doi: 10.1016/j.intimp.2025.115144.
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.
仔猪早期断奶可导致肠道紊乱和功能障碍，并可能引发肠道疾病。虽然小豆蔻明（CDN）已显示出抗炎和抗氧化活性，但其缓解仔猪肠道屏障功能障碍和肠道炎症的潜力仍未得到研究。在本研究中，我们通过建立脂多糖（LPS）免疫应激模型，研究了CDN通过激活芳烃受体（AhR）/核因子E2相关因子2（Nrf2）/NLRP3炎性小体途径对断奶仔猪和IPEC-J2细胞肠道屏障功能的保护作用。将30只仔猪随机分为五组，为期15天：基础日粮组（CON）、LPS攻毒组（LPS）、FICZ + LPS攻毒组（FICZ）、低剂量（3 mg/kg）CDN + LPS攻毒组（LCDN）和高剂量（6 mg/kg）CDN + LPS攻毒组（HCDN）。从第8天起，FICZ、LCDN和HCDN组的仔猪每天注射一次FICZ或CDN。在第15天，除CON组外，所有仔猪腹腔注射100 μg/kg体重的LPS，CON组注射等量的生理盐水。我们的结果表明，腹腔注射CDN可改善LPS诱导的肠道屏障功能，增强肠道抗氧化能力，并抑制炎症反应。此外，CDN上调AhR表达并抑制炎性小体激活。体外实验表明，AhR拮抗剂CH223191显著逆转了CDN对NLRP3炎性小体激活的抑制作用以及CDN介导的Nrf2核转位。此外，Nrf2抑制剂ML385消除了CDN对NLRP3炎性小体激活和炎性细胞因子产生的抑制作用。这些结果表明，CDN可通过AhR/Nrf2/NLRP3途径保护断奶仔猪的肠道屏障并减轻炎症。
