Saffron Petal, an Edible Byproduct of Saffron, Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting Macrophage Activation and Regulating Gut Microbiota

Saffron petal (SP) is an agricultural byproduct in theprocessof the crude drug saffron, accounting for 90% of the dry weight ofsaffron flowers. To promote the utilization of SP in the food andpharmaceutical industries, its anti-inflammatory activities were evaluatedon LPS-activated RAW 264.7 cells and DSS-challenged colitic mice.The results indicated that the SP extract had a notable effect inalleviating the clinical manifestations of colitis, such as reductionin body weight, improvement in disease activity index, mitigationof colon shortening, and alleviation of colon tissue damage. Moreover,SP extract significantly suppressed macrophage infiltration and activation,evidenced by a decrease in colonic F4/80 macrophages and suppressionof the transcription and secretion of colonic tumor necrosis factor-& alpha;(TNF-& alpha;), interleukin-1 & beta; (IL-1 & beta;), and interleukin-6(IL-6) in DSS-challenged colitic mice. In vitro,SP extract also significantly suppressed nitric oxide production,COX-2 and iNOS expressions, and TNF-& alpha; and IL-1 & beta; transcriptionof activated RAW 264.7 cells. Network pharmacology-guided researchidentified that SP extract significantly downregulated Akt, p38, ERK,and JNK phosphorylation in vivo and in vitro. In parallel, SP extract also effectively corrected microbial dysbiosisby increasing the abundance of Bacteroides acidifaciens, Bacteroides vulgatus, Lactobacillus murinus, and Lactobacillusgasseri. These findings indicate that the effectivenessof SP extract in treating colitis is demonstrated by its ability toreduce macrophage activation, inhibit the PI3K/Akt and MAPK pathways,and regulate gut microbiota, suggesting that SP extract holds greatpotential as a therapeutic option for colitis.