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姜黄素/氧化镁纳米颗粒对氯胺酮诱导的小鼠海马神经毒性的保护作用。

Protective effects of curcumin/magnesium oxide nanoparticles on ketamine-induced neurotoxicity in the mouse hippocampus.

作者信息

Salehirad Mahsa, Hayes A Wallace, Motaghinejad Majid, Gholami Mina

机构信息

Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Chemistry, Tehran Medical Sciences, Islamic Azad University, Tehran, I.R. Iran.

Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.

出版信息

Res Pharm Sci. 2025 Jun 17;20(3):416-433. doi: 10.4103/RPS.RPS_5_23. eCollection 2025 Jun.

Abstract

BACKGROUND AND PURPOSE

Nanotechnology can improve drug delivery by enhancing cell selectivity, releasing at specific target sites, and improving bioavailability while reducing adverse events and potential treatment costs. The current study aimed to synthesize curcumin/magnesium oxide (Cur/MgO) nanoparticles (NPs) and evaluate their neuroprotective effects in a mouse model of ketamine-induced neurotoxicity.

EXPERIMENTAL APPROACH

XRD, FE-SEM, and a particle size analyzer determined the average crystalline and particle sizes. UV-Vis examined absorption patterns, and FT-IR spectroscopy analyzed the functional groups involved in the reaction. To evaluate the effectiveness of Cur/MgO NPs on ketamine-induced neurotoxicity, male BALB/c mice were divided into 7 groups and received the following treatments (intraperitoneally, daily for 2 weeks). Groups 1 and 2 received normal saline (0.2 mL) and ketamine (25 mg/kg). Group 3 received curcumin (40 mg/kg) and ketamine (25 mg/kg). Groups 4-6 received ketamine (25 mg/kg) and Cur/MgO NPs (10, 20, and 40 mg/kg). Group 7 received MgO (5 mg/kg) and ketamine (25 mg/kg). Finally, the hippocampal tissues were examined morphologically and analyzed for oxidative stress, inflammation, apoptotic markers, and mitochondrial quadruple complex enzymes.

RESULTS/FINDINGS: Both Cur/MgO NPs and curcumin reduced IL-1β, TNF-α, Bax, and MDA levels and GSSG content and increased GSH, Bcl-2, GPx, GR, and SOD. Cur/MgO NPs and curcumin also increased mitochondrial quadruple complex enzymes and inhibited histological changes in the dentate gyrus and CA1 hippocampus areas in ketamine-induced neurotoxicity.

CONCLUSION AND IMPLICATIONS

Cur/MgO NPs were more neuroprotective against the ketamine-induced histomorphological changes, inflammation, apoptosis, and oxidative stress than curcumin alone.

摘要

背景与目的

纳米技术可通过增强细胞选择性、在特定靶点释放、提高生物利用度,同时减少不良事件和潜在治疗成本来改善药物递送。本研究旨在合成姜黄素/氧化镁(Cur/MgO)纳米颗粒(NPs),并在氯胺酮诱导的神经毒性小鼠模型中评估其神经保护作用。

实验方法

X射线衍射(XRD)、场发射扫描电子显微镜(FE-SEM)和粒度分析仪测定了平均晶体尺寸和粒径。紫外可见光谱(UV-Vis)检测吸收模式,傅里叶变换红外光谱(FT-IR)分析反应中涉及的官能团。为评估Cur/MgO NPs对氯胺酮诱导的神经毒性的有效性,将雄性BALB/c小鼠分为7组并接受以下处理(腹腔注射,每日1次,共2周)。第1组和第2组接受生理盐水(0.2 mL)和氯胺酮(25 mg/kg)。第3组接受姜黄素(40 mg/kg)和氯胺酮(25 mg/kg)。第4 - 6组接受氯胺酮(25 mg/kg)和Cur/MgO NPs(10、20和40 mg/kg)。第7组接受氧化镁(5 mg/kg)和氯胺酮(25 mg/kg)。最后,对海马组织进行形态学检查,并分析氧化应激、炎症、凋亡标志物和线粒体四重复合体酶。

结果/发现:Cur/MgO NPs和姜黄素均降低了白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、Bax和丙二醛(MDA)水平以及氧化型谷胱甘肽(GSSG)含量,并增加了谷胱甘肽(GSH)、Bcl-2、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽还原酶(GR)和超氧化物歧化酶(SOD)。Cur/MgO NPs和姜黄素还增加了线粒体四重复合体酶,并抑制了氯胺酮诱导的神经毒性中齿状回和海马CA1区的组织学变化。

结论与意义

与单独使用姜黄素相比,Cur/MgO NPs对氯胺酮诱导的组织形态学变化、炎症、凋亡和氧化应激具有更强的神经保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f47/12271846/9eb3e16866a1/RPS-20-416-g001.jpg

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