Synergistic effect of osthole and notopterol combination against Alzheimer's disease and osteoporosis by applying zebrafish AD/OP comorbidity model.

Autor: Guo LY; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, China., Wang T; School of Chinese Material Medica and Yunnan Key Laboratory of Southern Medicinal Resource, Yunnan University of Chinese Medicine, Kunming, 650000, China. Electronic address: wangt662@hotmail.com., Ma HX; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, China., Chen S; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, China., Chang ZY; Department of Orthopedics, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, Nanjing, 210029, China. Electronic address: changzhiyong1987@126.com., Li F; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, China; College of Pharmacy, Xinjiang Medical University, Urumqi, 830011, China. Electronic address: lifei@cpu.edu.cn.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Sep 15; Vol. 979, pp. 176829. Date of Electronic Publication: 2024 Jul 23.
DOI: 10.1016/j.ejphar.2024.176829
Abstrakt: Alzheimer's disease (AD) and osteoporosis (OP) are both serious degenerative diseases, with the potential for concurrent occurrence in clinical settings, and they share certain pathological correlations. Osthole (OST) and notopterol (NOT) are the main active ingredients in traditional Chinese medicine, Angelica pubescens and Notopterygium incisum, respectively, and they exhibit neuroprotective and osteoprotective effects. However, whether the combination of OST and NOT produces a synergistic effect against AD and/or OP remains unclear. The aim of this study was to investigate whether the combination of OST and NOT could produce synergistic anti-AD and/or OP effects using the previously constructed zebrafish AD/OP comorbidity model. Active compounds with anti-AD and OP effects were screened from Angelica pubescens and Notopterygium incisum through network pharmacology, identifying OST and NOT, respectively. Then, the AlCl 3 -induced (Aluminum chloride, AlCl 3 ) AD combined with OP zebrafish model, in conjunction with the Chou-Talalay synergy evaluation model, was employed to assess whether the OST and NOT combination produced synergistic effects against AD and/or OP. Furthermore, a CuSO 4 -induced (Copper sulfate, CuSO 4 ) inflammation zebrafish model was used to investigate whether the combination of OST and NOT produced synergistic anti-inflammatory effects, thereby resulting in synergistic anti-AD and/or OP effects. The results demonstrated that the OST-NOT combined treatment produced a synergistic anti-AD and OP effect. Moreover, the combined treatment of OST and NOT significantly inhibited nitric oxide (NO) and reactive oxygen species (ROS) release more effectively than OST or NOT alone, indicating a synergistic anti-inflammatory effect of the OST and NOT combined treatment.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Li-ying Guo, Ting Wang*, Hou-xu Ma, Shihao Chen, Zhi-yong Chang* and Fei, Li*
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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