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基于体内和分子对接分析的诃子(使君子科)水醇提根皮的伤寒治疗作用。

Curative anti-typhoid effect of Detarium microcarpum Guill. & Perr. (Leguminosae) hydroethanolic extract root bark based-on in vivo and molecular docking analyses.

机构信息

Department of Microbiology, Faculty of Science, University of Yaounde I, P.O. Box 812, Yaoundé, Cameroon; Department of Animal Biology and Physiology, Faculty of Science, University of Yaounde I, P.O. Box 812, Yaoundé, Cameroon; Department of Biochemistry, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Department of Biochemistry, Laboratory of Biochemistry, Faculty of Science, University of Douala, PO Box 24 157, Douala, Cameroon.

Department of Animal Biology and Physiology, Faculty of Science, University of Yaounde I, P.O. Box 812, Yaoundé, Cameroon; Department of Biochemistry, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.

出版信息

J Ethnopharmacol. 2023 May 10;307:116209. doi: 10.1016/j.jep.2023.116209. Epub 2023 Jan 24.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Detarium microcarpum is used to treat typhoid fever, a major public health problem, by indigenous population in Africa. Though its preventive activities have been documented, the curative effect is still to be confirmed.

AIM OF THE STUDY

This study aimed at evaluating the curative effects of the hydroethanolic extract of Detarium microcarpum root bark on Salmonella typhimurium-induced typhoid in rat and exploring the in-silico inhibition of some bacterial key enzymes.

STUDY DESIGN

In vitro antioxydant, in vivo antisalmonella of the extract and in silico molecular docking assay on the isolated compounds were carried out to explore the anti-salmonella effects of Detarium microcarpum.

MATERIAL AND METHODS

The in vitro antioxidant properties of the extract were evaluated using DPPH, ABTS and FRAP tests. The anti-salmonella activity of the extract was assessed through feacal sample from Salmonella typhimurium-infected rat cultured in Salmonella-Shigella agar (SS agar) medium. The affinity of isolated compounds (Rhinocerotinoic acid and Microcarposide) from the extract were performed on four key enzymes (Adenylosuccinate lyase, Acetyl coenzyme A synthetase, Thymidine phosphorylase and LuxS-Quorum sensor) using molecular docking simulation to elucidate the molecular level inhibition mechanism.

RESULTS

Crude extract of D. microcarpum root bark showed variable activities on DPPH (RSa50: 6.09 ± 1.04 μg/mL), ABTS (RSa50: 24.46 ± 0.27), and FRAP (RSa50: 23.30 ± 0.23). The extract at all the doses exhibited significant healing effect of infected rats, with the complete clearance. The extract restored hematological, biochemical and histological parameters closed to the normal control. The molecular docking results indicates that rhinocerotinoic acid and microcarposide present more affinity to the LuxS-Quorum sensor and Acetyl coenzyme A synthetase protein as compared to the others.

CONCLUSION

These results demonstrate potent anti-typhoid activities of the hydroethanolic of Detarium microcarpum root bark extract through antioxidant properties and high inhibitory affinity of its compounds on some bacterial key enzymes that justify its use as traditional medicine to typhoid fever.

摘要

民族药理学相关性

在非洲,土著居民用 Detarium microcarpum 来治疗伤寒,这是一个主要的公共卫生问题。虽然已经有文献记载了其预防作用,但疗效仍有待证实。

目的

本研究旨在评估 Detarium microcarpum 根皮的水醇提取物对鼠伤寒沙门氏菌引起的伤寒的治疗效果,并探索其对一些细菌关键酶的体外抑制作用。

研究设计

进行了提取物的体外抗氧化、体内抗沙门氏菌作用以及从提取物中分离出的化合物的计算机分子对接试验,以探索 Detarium microcarpum 的抗沙门氏菌作用。

材料和方法

采用 DPPH、ABTS 和 FRAP 试验评估提取物的体外抗氧化特性。通过在沙门氏菌-志贺氏菌琼脂(SS 琼脂)培养基中培养鼠伤寒沙门氏菌感染大鼠的粪便样本,评估提取物的抗沙门氏菌活性。使用分子对接模拟,对从提取物中分离出的化合物(犀角酸和 Microcarposide)对 4 种关键酶(腺苷酸琥珀酸裂解酶、乙酰辅酶 A 合成酶、胸苷磷酸化酶和 LuxS-群体感应传感器)的亲和力进行了研究,以阐明分子水平的抑制机制。

结果

D.microcarpum 根皮的粗提取物在 DPPH(RSa50:6.09±1.04μg/mL)、ABTS(RSa50:24.46±0.27)和 FRAP(RSa50:23.30±0.23)上表现出不同的活性。提取物在所有剂量下均对感染大鼠表现出显著的治疗效果,完全清除了感染。提取物恢复了接近正常对照的血液学、生化学和组织学参数。分子对接结果表明,与其他酶相比,犀角酸和 Microcarposide 对 LuxS-群体感应传感器和乙酰辅酶 A 合成酶蛋白具有更高的亲和力。

结论

这些结果表明,Detarium microcarpum 根皮的水醇提取物通过抗氧化特性和其化合物对一些细菌关键酶的高抑制亲和力表现出强烈的抗伤寒活性,证明其可作为治疗伤寒的传统药物。

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