Halorotetin B is a natural terpenoid compound isolated from the tunic of Halocynthia roretzi. Studies have shown that this compound exhibits significant anti-tumor activity. However, its anti-inflammatory potential remains unexplored, likely owing to the multi-target nature of natural compounds. In this study, we investigated the anti-inflammatory activity of Ha. B. The results showed that Ha. B significantly inhibited the production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells. Mechanistically, network pharmacology analysis and Western blot assays verified that Ha. B exerts its anti-inflammatory function by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Finally, natural product target prediction revealed that Ha. B may directly target mouse double minute 2 (MDM2). Cellular thermal shift assay (CETSA) results confirmed that Ha. B could interact with MDM2 in cells, and molecular docking was performed to simulate their physical binding mode. Meanwhile, RNA interference experiments further verified that Ha. B exerts its anti-inflammatory activity through binding to the E3 ubiquitin ligase MDM2.
| 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 |