OBJECTIVE To elucidate the pharmacodynamic substance basis of Aconiti Kusnezoffii processed with Terminalia chebula using plant metabolomics technology combined with bioinformatic analysis and in vitro activity validation methods. METHODS Firstly, high throughput data were collected from the aqueous extracts of A. Kusnezoffii processed with T. chebula before and after concoction based on liquid chromatography-mass spectrometry(LC-MS), and multivariate statistical analysis combined with univariate analysis was utilized to screen for differences in chemical components before and after the concoction. Secondly, based on the screened different chemical components, bioinformatic analysis and simulated molecular docking technology were used to analyze the potential pharmacodynamic components, targets and signaling pathways of A. Kusnezoffii processed with T. chebula for the treatment of rheumatoid arthritis. Finally, the pharmacodynamics was verified by in vitro cellular anti-inflammatory activity and antioxidant activity assays. RESULTS A total of 64 differential chemical components including alkaloids, organic acids and sugar components were screened before and after the preparation of A. Kusnezoffii. A. Kusnezoffii processed with T. chebula may exert its therapeutic effects on rheumatoid arthritis by regulating the abnormal expression of proteins such as TP53, ESR1, HSP90AA1, and PIK3R1, via cancer signaling pathway, metabolic signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and RAS signaling pathway. Both the aqueous extracts of A. Kusnezoffii before and after concoction significantly inhibited LPS-induced release of inflammatory factors such as NO, TNF-α, IL-6, and IL-1β, as well as possessed significant scavenging ability for DPPH radicals, hydroxyl radicals, and superoxide anion. CONCLUSION The pharmacodynamic material basis of A. Kusnezoffii processed with T. chebula is clarified, which provides a theoretical basis for the safe and effective clinical application of A.Kusnezoffii.
| 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 |