Impact of andrographolide on intestinal inflammation in rats with diarrhea type irritable bowel syndrome by regulating the NLRP3/caspase-1 signaling pathway
Objective To investigate the impact of andrographolide(AND)on intestinal inflammation in rats with diarrhea type irritable bowel syndrome(IBS-D)and its regulatory mechanism on the NLRP3/caspase-1 signaling pathway.Methods After the IBS-D rat model was established by low concentration acetic acid com-bined with restraint stress,the rats were grouped into control group,model group,positive drug group,AND low-dose(AND-L)group,AND medium dose(AND-M)group,and AND high-dose(AND-H)group,with 10 rats in each group.The score of fecal traits and fecal water content of rats in each group were detected;the abdominal with-drawal reflex(AWR)of rats in each group was scored;HE staining was applied to observe the changes of colonic histopathology of rats in each group;enzyme linked immunosorbent assay(ELISA)was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β),and interleukin-18(IL-18)in the colon tissue of rats in each group;Western blot was applied to detect the expression levels of NLRP3,ASC,and caspase-1 proteins in the colon tissue of rats in each group.Results The scores of fecal traits of rats in the control group was 2.43±0.19,fecal water content was 31.76±2.81,AWR score was 0.43±0.02,TNF-α was 123.49±12.35,IL-6 was 76.45±6.23,IL-1β was 195.76±15.14 and IL-18 was 167.31±13.92,the protein expression levels of NL-RP3 was 0.96±0.06,ASC was 1.01±0.08,and caspase-1 was 0.94±0.06.The scores of fecal traits in model group was 6.12±0.58,fecal water content was 65.24±4.13,AWR score was 2.42±0.18,which were higher than those in control group(P<0.05),the TNF-α in model group was 315.73±19.47,IL-6 was 231.97±14.65,IL-1β was 435.83± 28.67,IL-18 was 382.56±26.84,the protein expression levels of NLRP3 was 2.41±0.18,ASC was 2.23±0.15,and caspase-1 was 2.15±0.16,which were higher than those in control group(P<0.05).The scores of fecal traits in the low,medium,and high dose AND groups were 5.38±0.46,4.57±0.38,3.31±0.27,fecal water content were 54.68± 3.67,46.87±3.75,38.11±3.10,AWR scores were 1.79±0.16,1.35±0.10,0.69±0.04,which were higher than those in model group(P<0.05),the TNF-α in the low,medium,and high dose AND groups were 268.65±17.23,224.91± 16.36,178.16±14.65,IL-6 were 187.74±14.57,159.64±11.39,124.18±8.62,IL-1β were 369.51±21.96,314.72± 23.64,263.93±16.82,IL-18 were 334.72±25.17,280.16±21.43,235.67±19.32,the protein expression levels of NL-RP3 were 1.94±0.15,1.56±0.12,1.25±0.09,ASC were 1.89±0.14,1.61±0.13,1.28±0.10,and caspase-1 were 1.76± 0.14,1.49±0.11,1.20±0.09,which were higher than those in model group(P<0.05).Conclusion AND may alle-viate intestinal inflammation in IBS-D rats by inhibiting the NLRP3/caspase-1 signaling pathway.
AndrographolideNOD like receptor protein 3/caspase-1 signaling pathwayDiarrhea type irritable bowel syndromeIntestinal inflammation