1. Ramifloraolides A - D, four highly oxygenated picrotoxane-type sesquiterpenoids from the stems of Baccaurea ramiflora and their antithrombotic activity.
- Author
-
Su LH, Wang W, Yang YL, Chu MR, Wang YC, Lv HH, Zhou ZA, Chen H, Dai SX, and Xu M
- Subjects
- Animals, Mice, Molecular Structure, Structure-Activity Relationship, Dose-Response Relationship, Drug, Thrombosis drug therapy, Molecular Docking Simulation, Oxygen chemistry, Male, Sesquiterpenes chemistry, Sesquiterpenes pharmacology, Sesquiterpenes isolation & purification, Plant Stems chemistry, Fibrinolytic Agents pharmacology, Fibrinolytic Agents chemistry, Fibrinolytic Agents isolation & purification
- Abstract
A phytochemical investigation of the ethanol extract from air-dried stems of Baccaurea ramiflora led to the isolation of four highly oxygenated picrotoxane-type sesquiterpenoids, ramifloraolides A - D (1-4). Their structures were elucidated by comprehensive spectroscopic data (HRESIMS, IR, 1D, and 2D NMR), and their absolute configuration of them were unambiguously determined by single-crystal X-ray diffraction. Structurally, all compounds possess a unique [4.3.0] bicyclic core along with a characteristic γ-lactone. Notably, compound 1 is a picrotoxane sesquiterpenoid incorporating a rare oxygen bridge and a pentadecolactone. Compounds 2-4 possess a five-membered ether ring and the pentadecolactone, while ramifloraolides C (3) and D (4) were nor-picrotoxane. Then, the isolated phytochemicals were evaluated for antithrombotic activity in vivo. Interestingly, compounds 1 and 2 displayed potent antithrombotic activity at 30 μM in a zebrafish model. Additionally, 1 and 2 demonstrated certain antithrombotic effects in a mouse model of thrombosis. This marked the first report on the anti-thrombotic activity of picrotoxane-type sesquiterpenoids. Furthermore, network pharmacological and molecular docking analysis revealed potent target of those compounds associated with thrombotic disease. These finding initially demonstrate the potential of picrotoxanes as naturally derived antithrombotic lead compounds, and highlight the significant research values of sesquiterpenoids from the Baccaurea genus for comprehensive exploration of their application in antithrombotic therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2025
- Full Text
- View/download PDF