Coptisine attenuates post‑infectious IBS via Nrf2‑dependent inhibition of the NLPR3 inflammasome.

Abstract

Inhibition of the activation of the NLR family pyrin domain‑containing 3 (NLRP3) inflammasome has previously been reported to confer protection against post‑infectious irritable bowel syndrome (PI‑IBS). Coptisine, the second most abundant isoquinoline alkaloid in Coptischinensis, can inhibit NLRP3 inflammasome activation; however, whether coptisine exhibits protective effects against PI‑IBS remains unclear. In the present study, coptisine significantly reduced gastrointestinal motility and abdominal withdrawal reflex scores in a PI‑IBS rat model that was induced using intragastric administration of Trichinellaspiralis larvae. Coptisine treatment significantly decreased the protein levels of oxidative stress markers, 4‑hydroxynonenal, protein carbonyl and 8‑hydroxy‑2'deoxyguanosine, and proinflammatory cytokines, TNF‑α, IL‑1β and IL‑18 in the colon of PI‑IBS rats. Moreover, coptisine treatment significantly increased nuclear factor erythroid 2‑related factor 2 (Nrf2) nuclear translocation and heme oxygenase‑1 protein expression levels, while significantly downregulating the protein expression levels of NLRP3, apoptosis‑associated speck‑like protein containing a CARD and caspase‑1 in the colons of PI‑IBS rats. It is important to note that the anti‑inflammatory effects of coptisine were blocked by the Nrf2 inhibitor ML385. In summary, the present study indicated that coptisine potentially attenuated PI‑IBS in rats via Nrf2‑dependent inhibition of the NLPR3 inflammasome.