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苦木苦味素 A-M:药理学、作用机制、合成进展及药代动力学研究进展综述。

The quassinoids bruceines A-M: pharmacology, mechanism of action, synthetic advance, and pharmacokinetics-a review.

机构信息

Faculty of Chemistry, Hanoi Pedagogical University 2 (HPU2), 32 Nguyen Van Linh, Xuanhoa, Phucyen, Vinhphuc, Vietnam.

Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Caugiay, Hanoi, Vietnam.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec;397(12):9417-9433. doi: 10.1007/s00210-024-03281-7. Epub 2024 Jul 10.

Abstract

Bruceines A-L are among the quassinoid representatives found in the medicinal plant Brucea javanica (L.). An overview of their pharmacological activities is still unknown. The given research deals with highlights in their pharmacological result, molecular mechanism of action, synthetic progress, and pharmacokinetics. From previous evidence, bruceine derivatives are potential agents for anticancer treatments, as well as they are appropriate to treat inflammation, diabetes, and parasitic infections, and protect the neurons, kidneys, and lungs. Cytokine inhibitions, oxidative stress responses, and various signaling pathways, such as MAPK (mitogen-activated protein kinase) and NF-κB (nuclear factor-kappa B), have been proposed as the underlying mechanisms of action. Synthetic approaches to synthesize new derivatives with enhancement activities are based on free hydroxyl group modifications. Bruceines seem to be promptly absorbed by both oral and intravenous administrations, but their bioavailability is not high (less than 6%). Pre-clinical and clinical studies to prove their anticancer potential and other activities are urgent. Structural modifications, nano-combinations, and synergistic effects are necessary.

摘要

Bruceines A-L 是在药用植物苦木(Brucea javanica(L.))中发现的三萜类化合物代表之一。它们的药理学活性概述仍然未知。本研究重点介绍了它们的药理学结果、作用机制、合成进展和药代动力学。从以前的证据来看,Brucea 衍生物是癌症治疗的潜在药物,也适合治疗炎症、糖尿病和寄生虫感染,以及保护神经元、肾脏和肺部。细胞因子抑制、氧化应激反应和各种信号通路,如 MAPK(丝裂原激活的蛋白激酶)和 NF-κB(核因子-κB),被认为是其作用机制。基于游离羟基修饰的合成方法可用于合成具有增强活性的新衍生物。Bruceines 似乎可以通过口服和静脉给药迅速吸收,但生物利用度不高(低于 6%)。需要进行临床前和临床研究来证明其抗癌潜力和其他活性。结构修饰、纳米组合和协同作用是必要的。

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