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千里光(菊科)的馏分诱导大鼠线粒体介导的细胞凋亡:在谷氨酸单钠诱导的肝和子宫病理紊乱中的可能选择。

Fractions of Ageratum conyzoides L. (Compositae) induce mitochondrial-mediated apoptosis in rats: Possible option in monosodium glutamate-induced hepatic and uterine pathological disorder.

机构信息

Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria.

出版信息

J Ethnopharmacol. 2021 Sep 15;277:114192. doi: 10.1016/j.jep.2021.114192. Epub 2021 May 8.

DOI:10.1016/j.jep.2021.114192
PMID:33974943
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Several pathological disorders have been attributed to either oxidative stress or defect in apoptotic signaling pathway. Some bioactive compounds elicit their antiproliferative properties by induction of apoptosis via mitochondrial permeability transition (mPT) pore opening.

AIM OF STUDY

The present study therefore investigated the effects of various fractions of methanol extract of Ageratum conyzoides L. (MEAC) on mitochondrial-mediated apoptosis and the possible protective potential of the most potent against monosodium glutamate (MSG)-induced hepatic damage and uterine pathological disorder. The plant is folklorically used in the treatment of cancer and gynecological disorder.

MATERIALS AND METHODS

The MEAC was partitioned in succession and concentrated at 40 °C to obtain chloroform(CFAC), ethylacetate(EFAC) and methanol(MFAC) fractions. Mitochondria were isolated by differential centrifugation. The opening of mPT pore, mATPase activity and hepatic DNA fragmentation were assessed spectrophotometrically. Caspases 9 and 3, SOD and GSH-Px activities and MDA level were determined using ELISA technique. Histological assessment of the liver and uterine sections and GC-MS analysis of the most potent fraction were carried out.

RESULTS

The investigation showed that oral administration of the fractions caused induction of mPT pore opening, enhanced mATPase activity, upregulated the activities of caspases 9 and 3 and also, caused hepatic DNA fragmentation with CFAC being the most potent. The CFAC reversed severe MSG-induced hepatic damage and uterine hyperplasia. The MSG-induced oxidative stress was normalized by CFAC. The GC-MS analysis of CFAC revealed the presence of some pharmacologically relevant phytochemicals.

CONCLUSION

These findings therefore suggest that fractions of Ageratum conyzoides induce mitochondrial-mediated apoptosis. Moreover, CFAC, which is the most potent has a promising antioxidant and antiproliferative potential against MSG-induced hepatic and uterine pathological disorder.

摘要

民族药理学相关性

几种病理紊乱要么归因于氧化应激,要么归因于凋亡信号通路的缺陷。一些生物活性化合物通过诱导线粒体通透性转换(mPT)孔开放来发挥其抗增殖特性。

研究目的

因此,本研究调查了甲醇提取物的不同部位对 Ageratum conyzoides L.(MEAC)对线粒体介导的凋亡的影响,以及对谷氨酸单钠(MSG)诱导的肝损伤和子宫病理紊乱最有效的部位的可能保护潜力。该植物在民间用于治疗癌症和妇科疾病。

材料和方法

MEAC 依次进行分配,并在 40°C 浓缩,得到氯仿(CFAC)、乙酸乙酯(EFAC)和甲醇(MFAC)部分。通过差速离心分离线粒体。通过分光光度法评估 mPT 孔的开放、mATP 酶活性和肝 DNA 片段化。使用 ELISA 技术测定 caspase 9 和 3、SOD 和 GSH-Px 活性和 MDA 水平。对肝和子宫切片进行组织学评估,并对最有效的部位进行 GC-MS 分析。

结果

研究表明,各部位的口服给药会导致 mPT 孔开放诱导、增强 mATP 酶活性、上调 caspase 9 和 3 的活性,并导致肝 DNA 片段化,其中 CFAC 的作用最强。CFAC 逆转了 MSG 诱导的严重肝损伤和子宫增生。CFAC 使 MSG 诱导的氧化应激正常化。CFAC 的 GC-MS 分析表明存在一些具有药理相关性的植物化学物质。

结论

因此,这些发现表明 Ageratum conyzoides 的部位诱导线粒体介导的凋亡。此外,CFAC 是最有效的部位,具有对抗 MSG 诱导的肝和子宫病理紊乱的有希望的抗氧化和抗增殖潜力。

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