在大鼠肝脏中,藏红花通过靶向氧化应激相关的PI3K/Akt/mTOR信号通路,减少地西泮诱导的磷脂质溶解症生物标志物水平。
Crocin lessens desipramine-induced phospholipidosis biomarker levels via targeting oxidative stress- related PI3K/Akt/mTOR signaling pathways in the rat liver.
发表日期:2023 Apr 24
作者:
Rowida Raafat Ibrahim, Amal Ahmed El-Sheikh, Heba A Mahmoud, Eman Ali El-Kordy, Amal M Abdelsattar, Fatma H Rizk, Radwa Mahmoud El-Sharaby, Shimaa S Mashal, Amira A El Saadany, Rania H Shalaby, Amira M Elshamy, Omnia Safwat El-Deeb, Hoda A Ibrahim
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
背景和目的:藏红花中含有一种药理活性化学物质——红花醛,具有抗氧化和抗自由基性能,能够减轻三环类抗抑郁药异卡特平引起的肝脏磷脂质沉积症。本研究的目的是研究红花醛对异卡特平引起的肝脏磷脂质沉积症的影响,重点关注与氧化应激相关的PI3K/Akt/mTOR信号通路。将40只成年雄性大鼠分为四组(n=10):对照组,腹腔注射红花醛组(50毫克/千克/天),腹腔注射异卡特平组(10毫克/千克/天)和同时注射红花醛和异卡特平的组。经过三周的治疗后,联合治疗组显示出减少异卡特平引起的肝脏磷脂质沉积症,以及显著降低总氧化状态(TOS)、炎症标记物IL6、TNF-α和凋亡标记物caspase3和Bcl2(B细胞淋巴瘤2)水平,而其他标记物包括总抗氧化能力(TAC)、超氧化物歧化酶(SOD)、磷脂酰肌醇3-激酶(PI3K)和哺乳动物雷帕霉素靶蛋白(mTOR)则升高。与异卡特平组相比,联合治疗组的溶酶体酶基因表达(包括ELOVL6、SCD1和HMGR)明显下调,而AP1S1则上调。联合治疗组中未出现多层体的肝脏磷脂质沉积体的超微结构迹象。这些数据表明,红花醛对异卡特平引起的磷脂质沉积症具有保护作用。
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.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.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.These data collectively suggest that crocin has a protective effect against desipramine-induced phospholipidosis. (www.actabiomedica.it).