This study was to investigate the protective effect of Saposhnikovia divaricata (Turcz.) Schischk. (SD) on ulcerative colitis (UC) and its relationship with aryl hydrocarbon receptor (AHR)/NOD-like receptor family, pyrin domain containing 3 (NLRP3) pathway. The acute colitis model of C57BL/6J mice was established by continuous drinking water with 2.5% dextran sulfate sodium (DSS) for 7 days. At the same time, the ethanol extract of Saposhnikovia divaricata (2 and 5 g·kg-1·d-1) or 5-aminosalicylic acid (5-ASA, 100 mg·kg-1·d-1) was given by gavage. Body weight and disease activity index (DAI) were recorded. Colon length, hematoxylin-eosin (HE) and Alcian blue-periodic acid-Schiff staining (AB-PAS) staining and immunofluorescence were used to evaluate colon tissue damage and changes of goblet cells and tight junction proteins. ELISA, RT-qPCR and Western blot were used to analyze the expression of inflammatory factors, tight junction proteins and AHR/NLRP3-related molecules in serum and colon tissues. The use of animals in this study was approved by the Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval number: PZSHUTCM2510310022). The results showed that compared with the DSS model group, Saposhnikovia divaricata could dose-dependently reduce DSS-induced weight loss and DAI increase, prolong colon length, and reduce mucosal pathological damage. At the same time, it down-regulated the expression of inflammatory factors such as TNF-α, IL-1β and IL-6 in serum and colon tissues, up-regulated the mRNA and protein levels of zonula occludens-1 (ZO-1) and occludin tight junction proteins, and increased the expression of AHR protein, and inhibited NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1 and IL-1β. In AHR knockout mice, the alleviation effect of the ethanol extract of Saposhnikovia divaricata on DSS-induced acute ulcerative colitis in mice was not observed. In summary, Saposhnikovia divaricata may inhibit the activation of downstream NLRP3 inflammasome by activating AHR, thereby maintaining intestinal mucosal barrier function and reducing intestinal inflammation, providing experimental basis for its application in the prevention and treatment of UC.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |