葡萄籽提取物中的纳米颗粒可抑制炎性细胞因子并改善四氯化碳诱导的肝毒性。

Nanoparticles from grape seed extract inhibit inflammatory cytokines and ameliorate CCl-induced hepatotoxicity.

作者信息

Madbouly Neveen Adel, Ali Doaa Mohammad, Farid Alyaa Ahmed

机构信息

Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt.

Biotechnology Department, Faculty of Science, Cairo University, Giza, Egypt.

出版信息

BMC Complement Med Ther. 2025 Jul 19;25(1):276. doi: 10.1186/s12906-025-05005-7.

DOI:10.1186/s12906-025-05005-7

PMID:40684220

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12275419/

Abstract

BACKGROUND

Xenobiotic-induced liver injury is a clinically reverent condition which may influence the development of steatohepatitis via affecting numerous pathways such as oxidative stress, inflammation, mitochondorial functioning and fatty acid biosynthesis. The current study was conducted to survey the antioxidant effect of grape seeds extract nanoparticles (GS extract NPs) against CCl-induced oxidative stress, hepatic dysfunction and inflammatory changes.

METHODS

Hydroethanolic Grape seed (GS) extract was prepared and characterized using high performance liquid chromatography (HPLC), inductively coupled plasma-mass spectrometry (ICP-MS) and gas chromatography-mass spectrometry (GC-MS). Then, GS extract NPs were synthesized and in vitro antioxidant, anticoagulant, cytotoxicity and anti-inflammatory testes confirmed biological activity. Finally, Twenty-five male Sprague-Dawley rats were divided into five groups (n = 5/group). Either GS extract (200 mg/kg/day) or GS extract NPs (100 mg/kg/day) were orally administrated independently to CCL-intoxicated (0.5 ml/kg twice a week for 3 weeks) rats. Four weeks after the treatment, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) were monitored. In addition, hepatic Malondialdehyde (MDA), Superoxide dismutases (SOD), Glutathione (GSH) and catalase (CAT) and hepatic inflammatory cytokines were assessed.

RESULTS

GS extract NPs were spherical-shaped and regular particles (size: 16.5 to 22.5 nm and zeta potential: -39.42 mv). CCL -intoxicated rats showed increase of serum ALT, AST, ALP, elevation in MDA level accompanied by a decline in SOD, GSH and CAT levels in liver, compared with CCL-untreated rats. Immunologically, serum C-Reactive Protein (CRP) and hepatic interleukin 1β (IL-1β), IL-4, IL-6 and Tumor Necrosis Factor-alpha (TNF-α) showed significant elevation, compared with CCL -untreated rats. Conversely, GS extract NPs supplementation potentially ameliorate hepatic functions by normalization of serum ALT, AST and ALP, reduced MDA level, improved antioxidant CAT, regulated liver inflammatory cytokines via maximal reduction of hepatic IL-1β, IL-4, IL-6 and TNF-α.

CONCLUSION

GS extract NPs augmented the antioxidant and anti-inflammatory properties of GS extract thereby protecting the liver against oxidative stress induced by CCl as hepatic xenobiotic.

CLINICAL TRIAL NUMBER

Not applicable.

摘要

背景

外源性物质诱导的肝损伤是一种临床相关病症，可通过影响氧化应激、炎症、线粒体功能和脂肪酸生物合成等多种途径影响脂肪性肝炎的发展。本研究旨在探讨葡萄籽提取物纳米颗粒（GS提取物NPs）对四氯化碳诱导的氧化应激、肝功能障碍和炎症变化的抗氧化作用。

方法

制备水乙醇葡萄籽（GS）提取物，并采用高效液相色谱（HPLC）、电感耦合等离子体质谱（ICP-MS）和气相色谱-质谱（GC-MS）进行表征。然后，合成GS提取物NPs，并通过体外抗氧化、抗凝、细胞毒性和抗炎试验证实其生物活性。最后，将25只雄性Sprague-Dawley大鼠分为五组（每组n = 5）。将GS提取物（200mg/kg/天）或GS提取物NPs（100mg/kg/天）分别口服给予四氯化碳中毒（0.5ml/kg，每周两次，共3周）的大鼠。治疗四周后，监测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）水平。此外，还评估了肝脏丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、过氧化氢酶（CAT）以及肝脏炎症细胞因子。

结果

GS提取物NPs呈球形且规则（尺寸：16.5至22.5nm，ζ电位：-39.42mv）。与未用四氯化碳处理的大鼠相比，四氯化碳中毒的大鼠血清ALT、AST、ALP升高，肝脏MDA水平升高，同时SOD、GSH和CAT水平下降。在免疫方面，与未用四氯化碳处理的大鼠相比，血清C反应蛋白（CRP）以及肝脏白细胞介素1β（IL-1β）、IL-4、IL-6和肿瘤坏死因子-α（TNF-α）显著升高。相反，补充GS提取物NPs可通过使血清ALT、AST和ALP正常化、降低MDA水平、改善抗氧化酶CAT、通过最大程度降低肝脏IL-1β、IL-4、IL-6和TNF-α来调节肝脏炎症细胞因子，从而潜在地改善肝功能。