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红芪总皂苷通过内质网应激激活的细胞凋亡减轻顺铂诱导的小鼠肠道毒性。

Saponins From Reduces Cisplatin-Induced Intestinal Toxicity in Mice through Endoplasmic Reticulum Stress-Activated Apoptosis.

机构信息

College of Chinese Medicinal Materials, Jilin Agricultural University, P. R. China.

National & Local Joint Engineering Research, Center for Ginseng Breeding and Development, Changchun 130118, P. R. China.

出版信息

Am J Chin Med. 2022;50(7):1927-1944. doi: 10.1142/S0192415X22500823. Epub 2022 Sep 4.

DOI:10.1142/S0192415X22500823
PMID:36056466
Abstract

Saponins from the roots of , an edible medicinal plant, have shown a wide range of beneficial effects on various biological processes. In this study, an animal model was established by a single intraperitoneal injection of cisplatin (20[Formula: see text]mg/kg) for evaluating the protective effects of saponins from the roots of (PGS, 15[Formula: see text]mg/kg and 30[Formula: see text]mg/kg) in mice. The results indicated that PGS treatment for 10 days restored the destroyed intestinal mucosal oxidative system, and the loosened junctions of small intestinal villi was significantly improved. In addition, a significant mitigation of apoptotic effects deteriorated by cisplatin exposure in small intestinal villi was observed by immunohischemical staining. Also, western blot showed that PGS could effectively prevent endoplasmic reticulum (ER) stress-induced apoptosis caused by cisplatin in mice by restoring the activity of PERK (an ER kinase)-eIF2[Formula: see text]-ATF4 signal transduction pathway. Furthermore, molecular docking results of main saponins in PGS suggested a better binding ability with target proteins. In summary, the present work revealed the underlying protective mechanisms of PGS on intestinal injury induced by cisplatin in mice.

摘要

从食用药用植物 根茎中提取的皂素对各种生物过程表现出广泛的有益作用。在这项研究中,通过单次腹腔注射顺铂(20[Formula: see text]mg/kg)建立了动物模型,以评估 根茎皂素(PGS,15[Formula: see text]mg/kg 和 30[Formula: see text]mg/kg)对小鼠的保护作用。结果表明,PGS 治疗 10 天可恢复受损的肠道黏膜氧化系统,并显著改善小肠绒毛的松散连接。此外,通过免疫组织化学染色观察到,PGS 可显著减轻顺铂暴露引起的小肠绒毛细胞凋亡的影响。此外,Western blot 结果表明,PGS 可通过恢复 PERK(内质网激酶)-eIF2[Formula: see text]-ATF4 信号转导通路的活性,有效防止顺铂诱导的小鼠内质网应激诱导的细胞凋亡。此外,PGS 中主要皂素的分子对接结果表明其与靶蛋白具有更好的结合能力。总之,本研究揭示了 PGS 对顺铂诱导的小鼠肠道损伤的潜在保护机制。

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