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西红花苷通过靶向氧化应激相关的 PI3K/Akt/mTOR 信号通路降低去甲丙咪嗪诱导的大鼠肝脏磷脂蓄积生物标志物水平。

Crocin lessens desipramine-induced phospholipidosis biomarker levels via targeting oxidative stress- related PI3K/Akt/mTOR signaling pathways in the rat liver.

机构信息

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medical biochemistry.

出版信息

Acta Biomed. 2023 Apr 24;94(2):e2023141. doi: 10.23750/abm.v94i2.14442.

Abstract

UNLABELLED

Background and aim Crocin is a pharmacologically active chemical found in the spice saffron from Crocus sativus L. It possesses antioxidant and anti-radical properties that can minimize the hepatic phospholipidosis triggered using the tricyclic antidepressant desipramine. The aim of this study was to examine the effect of crocin on desipramine-induced hepatic phospholipidosis targeting the oxidative stress-related PI3K/Akt/mTOR signaling pathways.

METHODS

Forty adult male rats were divided into 4 groups (n =10): control group, a group receiving intraperitoneal (IP) crocin (50 mg/kg/day), a group receiving IP desipramine (10 mg/kg/day), and a group receiving both IP crocin and desipramine.

RESULTS

After 3 weeks of treatment, the combined treatment group showed diminished desipramine-induced hepatic phospholipidosis, along with significant reductions in total oxidant status (TOS) , the levels of inflammatory markers including interleukin 6 (IL6) and tumor necrosis factor α (TNF-α) and apoptotic markers including caspase3 and Bcl2 (B-cell lymphoma 2) while other markers including total antioxidant capacity (TAC), superoxide dismutase (SOD), phosphoinositide 3-kinases (PI3K), and mammalian target of rapamycin (mTOR) were increased. The gene expression of lysosomal enzymes including ELOVL6, SCD1 and HMGR was notably downregulated, while AP1S1 was upregulated in the combined treatment group compared to the desipramine group. No ultrastructural signs of hepatic phospholipidosis, in the form of multilamellar bodies, were apparent in the combined treatment group.

CONCLUSIONS

These data collectively suggest that crocin has a protective effect against desipramine-induced phospholipidosis. (www.actabiomedica.it).

摘要

未加标签

背景和目的 藏红花素是一种在藏红花(Crocus sativus L.)中发现的具有药理活性的化学物质。它具有抗氧化和抗自由基特性,可以最小化三环抗抑郁药去甲丙咪嗪引起的肝磷脂病。本研究旨在研究藏红花素对去甲丙咪嗪诱导的肝磷脂病的影响,针对氧化应激相关的 PI3K/Akt/mTOR 信号通路。

方法

将 40 只成年雄性大鼠分为 4 组(n = 10):对照组、腹腔内(IP)藏红花素(50mg/kg/天)组、腹腔内去甲丙咪嗪(10mg/kg/天)组和腹腔内藏红花素和去甲丙咪嗪联合组。

结果

经过 3 周的治疗,联合治疗组显示出减轻的去甲丙咪嗪诱导的肝磷脂病,同时总氧化状态(TOS)、炎症标志物包括白细胞介素 6(IL6)和肿瘤坏死因子 α(TNF-α)和凋亡标志物包括 caspase3 和 Bcl2(B 细胞淋巴瘤 2)水平显著降低,而其他标志物包括总抗氧化能力(TAC)、超氧化物歧化酶(SOD)、磷酸肌醇 3-激酶(PI3K)和雷帕霉素靶蛋白(mTOR)增加。与去甲丙咪嗪组相比,联合治疗组溶酶体酶的基因表达明显下调,包括 ELOVL6、SCD1 和 HMGR,而 AP1S1 上调。联合治疗组未出现多膜体形式的肝磷脂病的超微结构迹象。

结论

这些数据表明,藏红花素对去甲丙咪嗪诱导的磷脂病具有保护作用。(www.actabiomedica.it)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4844/10210559/9783014940b3/ACTA-94-141-g001.jpg

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