Ulcerative colitis (UC) is an intestinal disease characterized by chronic and recurrent inflammation of the colonic mucosal layer, whose main pathological feature is continuous and diffuse mucosal damage which begins in the rectum and extends towards the proximal colon. G-protein-coupled receptor 21 (GPR21) is an orphan G protein-coupled receptor (GPCR), belonging to class A GPCRs. Previous studies have reported that GPR21 is closely related to diabetes and inflammation. Levistilide A (LA), a natural terpene lactone active component mainly exists in the traditional Chinese medicinal herbs Ligusticum chuanxiong and Angelica sinensis, exhibiting multiple pharmacological activities including anti-inflammation, anti-fibrosis, and anti-tumor. In this study, GPR21-HEK293 recombinant cells were constructed by lentivirus transfection. LA was screened out as a potential GPR21 inhibitor by cell membrane chromatography. RAW264.7 cells were treated with lipopolysaccharide in vitro to establish an inflammatory cell model, which confirmed the correlation between the therapeutic effect of LA on inflammation and GPR21. Dextran sodium (DSS) was used to administrate C57BL/6 mice in vivo to induce a mouse model of UC, at the meanwhile, the mice in LA group were intragastrical administration with LA to investigate its therapeutic effect on UC. In conclusion, we demonstrated that LA as a GPR21 inhibitor improves DSS-induced UC through reducing intestinal inflammation. This work was approved by the Institutional Animals Care and Use Committee of Xi'an Jiaotong University (approval number: XJTUAE2024-1523) and strictly carried out in accordance with their requirements.
| 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 |