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衣饭树籽油提取物的药理学特性:通过调节氧化应激、炎症、细胞凋亡和 MAPK 信号通路对糖尿病的作用新见解。

Pharmacological properties of Ensete glaucum seed extract: Novel insights for antidiabetic effects via modulation of oxidative stress, inflammation, apoptosis and MAPK signaling pathways.

机构信息

National Institute of Medicinal Materials (NIMM), Hanoi, 100000, Viet Nam; Research Center of Ginseng and Medicinal Materials (CGMM), National Institute of Medicinal Materials, Ho Chi Minh City, 700000, Viet Nam.

Research Center of Ginseng and Medicinal Materials (CGMM), National Institute of Medicinal Materials, Ho Chi Minh City, 700000, Viet Nam.

出版信息

J Ethnopharmacol. 2024 Feb 10;320:117427. doi: 10.1016/j.jep.2023.117427. Epub 2023 Nov 20.

DOI:10.1016/j.jep.2023.117427
PMID:37992883
Abstract

ETHNOPHAMACOLOGICAL RELEVANCE

Medicinal plants are increasingly making important contributions to diabetic treatment. Ensete glaucum seeds have been widely used in folk medicine to treat diabetes.

AIM OF THE STUDY

The study was aimed to investigate the protective effect and active mechanisms of E. glaucum seed extract (EGSE) against streptozotocin (STZ)-induced hyperglycemia.

MATERIALS AND METHODS

Hyperglycemic mice were treated with EGSE (25 and 50 mg/kg) or glibenclamide (5 mg/kg) once daily for 7 d. The effects of these treatments on changes in blood biochemical parameters, pancreatic, liver, and kidney histopathology, oxidative stress and inflammatory marker levels in pancreatic, hepatic, and renal tissues were assessed. Expression of several proteins in MAPK signaling pathway related to apoptosis in pancreatic tissue were investigated. Furthermore, ex vivo, in vitro, and in silico biological activities of EGSE and its compounds were also examined.

RESULTS

EGSE and glibenclamide increased notably insulin, reduced significantly glucose, AST, ALT, BUN and creatinine levels in blood. Pancreatic islets, hepatic and renal tissue structure were restored by EGSE or glibenclamide. EGSE showed significant anti-oxidative stress and anti-inflammatory effects by enhancing GSH level and dropping MDA, NF-κB, TNF-α and IL-6 levels in these tissues. Particularly, EGSE exhibited pancreatic protective effect against STZ-induced apoptosis through the MAPK signaling pathway by down-regulation of p-p38 MAPK, ERK1/2, JNK1, p-AMPK, Bax, Bax/Bcl-2, cytochrome c, cleaved-caspase 3 and PARP expression, and slight up-regulation of Bcl-2 expression. Moreover, EGSE inhibited intestinal glucose absorption, PTP1B, α-amylase, and α-glucosidase activities. Its isolated compounds (Afzelechin and coniferaldehyde) showed PTP1B and α-glucosidase inhibitory activities, and potent structure-activity relationships.

CONCLUSION

These findings indicated the hypoglycemic and protective effects of E. glaucum seed extract against the STZ diabetogenic action. E. glaucum seed is a potential candidate for further studies to confirm its activities as a therapeutic agent for diabetic patients.

摘要

民族药理学相关性

药用植物在糖尿病治疗方面的作用日益重要。衣索比亚芭蕉的种子在民间医学中被广泛用于治疗糖尿病。

研究目的

本研究旨在探讨衣索比亚芭蕉种子提取物(EGSE)对链脲佐菌素(STZ)诱导的高血糖的保护作用及作用机制。

材料和方法

将高血糖小鼠用 EGSE(25 和 50mg/kg)或格列本脲(5mg/kg)每日一次处理 7 天。评估这些处理对血液生化参数变化、胰腺、肝脏和肾脏组织病理学、胰腺、肝脏和肾脏组织氧化应激和炎症标志物水平的影响。还研究了与胰腺组织细胞凋亡相关的 MAPK 信号通路中几种蛋白的表达。此外,还对 EGSE 及其化合物的离体、体外和计算生物学活性进行了检查。

结果

EGSE 和格列本脲显著增加了胰岛素,显著降低了血液中的葡萄糖、AST、ALT、BUN 和肌酐水平。衣索比亚芭蕉种子、肝和肾组织的结构通过 EGSE 或格列本脲得到恢复。EGSE 通过增强 GSH 水平并降低 MDA、NF-κB、TNF-α和 IL-6 水平,在这些组织中显示出显著的抗氧化应激和抗炎作用。特别是,EGSE 通过下调 p-p38 MAPK、ERK1/2、JNK1、p-AMPK、Bax、Bax/Bcl-2、细胞色素 c、cleaved-caspase 3 和 PARP 表达,并轻微上调 Bcl-2 表达,对 STZ 诱导的凋亡表现出胰腺保护作用。此外,EGSE 抑制了肠道葡萄糖吸收、PTP1B、α-淀粉酶和α-葡萄糖苷酶活性。其分离的化合物(阿夫泽林和松柏醛)表现出 PTP1B 和 α-葡萄糖苷酶抑制活性,以及很强的构效关系。

结论

这些发现表明衣索比亚芭蕉种子提取物对 STZ 致糖尿病作用具有降血糖和保护作用。衣索比亚芭蕉种子是进一步研究的潜在候选物,以确认其作为糖尿病患者治疗剂的活性。

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