Development of AKR1B10 inhibitors from Ajuga nipponensis based on diseases and targets.

Autor: Sun N; Food and Pharmacy College, Xuchang University, Xuchang, Henan 461000, People's Republic of China. Electronic address: sunna0876@163.com., Ma S; Food and Pharmacy College, Xuchang University, Xuchang, Henan 461000, People's Republic of China., Jin L; Food and Pharmacy College, Xuchang University, Xuchang, Henan 461000, People's Republic of China., Wang Y; Food and Pharmacy College, Xuchang University, Xuchang, Henan 461000, People's Republic of China., Zhou C; Food and Pharmacy College, Xuchang University, Xuchang, Henan 461000, People's Republic of China., Zhang X; Food and Pharmacy College, Xuchang University, Xuchang, Henan 461000, People's Republic of China., Kang H; Food and Pharmacy College, Xuchang University, Xuchang, Henan 461000, People's Republic of China., Zhou M; Food and Pharmacy College, Xuchang University, Xuchang, Henan 461000, People's Republic of China., Yang H; Food and Pharmacy College, Xuchang University, Xuchang, Henan 461000, People's Republic of China., Shu P; Food and Pharmacy College, Xuchang University, Xuchang, Henan 461000, People's Republic of China. Electronic address: shupenghua@yeah.net.
Jazyk: angličtina
Zdroj: Fitoterapia [Fitoterapia] 2024 Jan; Vol. 172, pp. 105742. Date of Electronic Publication: 2023 Nov 10.
DOI: 10.1016/j.fitote.2023.105742
Abstrakt: Ten compounds (1-10) including one new neoclerodane diterpenoid (1) and nine known compounds were isolated from the whole plants of Ajuga nipponensis. Their structures were established by performing detailed analysis of NMR, the structure of 1 was determined using HRESIMS, 1D and 2D NMR, UV, and IR. Compounds 1 and 4-10 were isolated from Ajuga nipponensis for the first time. And it was the first time to report compounds 9 and 10 as natural products. Based on network pharmacology methods, 45 key targets were selected, which were compounds mapping to diseases. And compounds 2, 3, 7, and a (ajugacumbin B) exhibited excellent AKR1B10 inhibitory activities, with IC 50 values of 53.05 ± 0.75, 87.22 ± 0.85, 61.85 ± 0.66, and 85.19±1.02 nM respectively, with Epalrestat used as the positive control (82.09 ± 1.62 nM). Additionally, the interaction between active compounds and AKR1B10 had been discussed according to the molecular docking results. Ultimately, the analysis of GO and KEGG enrichment indicated that the key signaling pathway of the active compounds may be related to prostate cancer. Our study results demonstrate the hypoglycemic and anti-tumor properties of A. nipponensis for the first time, and provide a comprehensive understanding of its application in traditional medicine. Furthermore, this article establishes a reference for further research on the optimized experimental design of novel AKR1B10 inhibitors.
Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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