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富含水飞蓟宾宁的种子提取物对四种肠道病毒株(肠道病毒71型、柯萨奇病毒B2型、柯萨奇病毒A10型和脊髓灰质炎病毒SL-1)的体外抗病毒活性及其对改善小鼠胃排空延迟的影响。

In Vitro Antiviral Activity of a Silydianin-Rich Extract from Seeds Against Four Strains of Enteroviruses: EV71, Coxsackievirus B2, Coxsackievirus A10, and Poliovirus SL-1 and Its Impact on Improving Delayed Gastric Emptying in Mice.

作者信息

Zaher Houda, Quílez Del Moral José Francisco, Lemrabet Sanae, Koutchala Neri, Bencharki Bouchaib

机构信息

Laboratory of Agro-Alimentary and Health, Faculty of Sciences and Techniques, Hassan First University of Settat, Settat 26000, Morocco.

Department of Organic Chemistry, Institute of Biotechnology, University of Granada, 18071 Granada, Spain.

出版信息

Antibiotics (Basel). 2025 Feb 14;14(2):196. doi: 10.3390/antibiotics14020196.

DOI:10.3390/antibiotics14020196
PMID:40001439
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11851915/
Abstract

BACKGROUND

Gastroparesis, a chronic digestive disorder characterized by delayed gastric emptying, often results from diabetes, post-surgical complications, autoimmune diseases, and neurological disorders. In approximately 50% of cases, the cause is idiopathic gastroparesis (IGD). Recent studies suggest a link between chronic enteroviral infection and persistent gastrointestinal symptoms, including delayed gastric emptying. This study investigates the effects of a silydianin-rich extract from seeds on enteroviral infections in vitro and the mitigation of delayed gastric emptying in mice. Silydianin, a key bioactive compound known for its liver-protective and antioxidant properties, has not been extensively studied for its impact on enteroviral infections and gastroparesis.

METHODS

NMR spectroscopy (H, C, DEPT 135 and 2D, and HSQC) and HRMS identified silydianin as the primary compound, with minor flavonolignans. This study assessed the cytotoxicity and antiviral activity of the extract at various stages of the viral life cycle, including virucidal activity, cell protection, and post-infection effects, using neutral red assays in RD cells, with results confirmed by real-time PCR. The viruses studied included coxsackievirus B2, coxsackievirus A10, poliovirus SL-1, and enterovirus EV71. The impact on delayed gastric emptying was evaluated in a mouse model using doses of 100 and 200 mg/kg compared to a control group receiving physiological saline.

RESULTS

The silydianin-rich extract showed consistent antiviral activity, with the highest selectivity index (SI) for EV71 (4.08) during virucidal activity. It provided moderate cell protection, with EC values ranging from 120.88 to 186.10 µg/mL and SI values from 2.20 to 3.39. Post-infection treatment showed varying efficacy, with coxsackie A10 demonstrating the highest SI (3.90). In vivo, the extract at 200 mg/kg significantly improved gastric emptying to 96.47% and slightly increased gastrointestinal transit from 50.33% to 61.46%.

CONCLUSIONS

These results suggest that silydianin may be effective for treating enteroviral infections and enhancing intestinal function, making it a promising candidate for gastroparesis treatment and warranting further research.

摘要

背景

胃轻瘫是一种以胃排空延迟为特征的慢性消化系统疾病,通常由糖尿病、术后并发症、自身免疫性疾病和神经系统疾病引起。在大约50%的病例中,病因是特发性胃轻瘫(IGD)。最近的研究表明,慢性肠道病毒感染与持续的胃肠道症状之间存在联系,包括胃排空延迟。本研究调查了一种富含水飞蓟宾的种子提取物对体外肠道病毒感染的影响以及对小鼠胃排空延迟的缓解作用。水飞蓟宾是一种以其肝脏保护和抗氧化特性而闻名的关键生物活性化合物,但其对肠道病毒感染和胃轻瘫的影响尚未得到广泛研究。

方法

核磁共振波谱法(H、C、DEPT 135和二维,以及HSQC)和高分辨率质谱法确定水飞蓟宾为主要化合物,还有少量黄酮木脂素。本研究使用RD细胞中的中性红试验评估了提取物在病毒生命周期各个阶段的细胞毒性和抗病毒活性,包括杀病毒活性、细胞保护和感染后效应,结果通过实时聚合酶链反应得到证实。所研究的病毒包括柯萨奇病毒B2、柯萨奇病毒A10、脊髓灰质炎病毒SL-1和肠道病毒EV71。与接受生理盐水的对照组相比,在小鼠模型中使用100和200毫克/千克的剂量评估对胃排空延迟的影响。

结果

富含水飞蓟宾的提取物表现出一致的抗病毒活性,在杀病毒活性期间对EV71的选择性指数(SI)最高(4.08)。它提供了适度的细胞保护,EC值范围为120.88至186.10微克/毫升,SI值为2.20至3.39。感染后治疗显示出不同的疗效,柯萨奇A10的SI最高(3.90)。在体内,200毫克/千克的提取物显著将胃排空改善至96.47%,并使胃肠道转运从50.33%略有增加至61.46%。

结论

这些结果表明,水飞蓟宾可能对治疗肠道病毒感染和增强肠道功能有效,使其成为胃轻瘫治疗的有希望的候选药物,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec70/11851915/861ebad12669/antibiotics-14-00196-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec70/11851915/351060324209/antibiotics-14-00196-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec70/11851915/45e631301e65/antibiotics-14-00196-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec70/11851915/635f645e859f/antibiotics-14-00196-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec70/11851915/8f5f0de0c4d3/antibiotics-14-00196-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec70/11851915/861ebad12669/antibiotics-14-00196-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec70/11851915/351060324209/antibiotics-14-00196-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec70/11851915/45e631301e65/antibiotics-14-00196-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec70/11851915/635f645e859f/antibiotics-14-00196-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec70/11851915/8f5f0de0c4d3/antibiotics-14-00196-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec70/11851915/861ebad12669/antibiotics-14-00196-g007.jpg

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In Vitro Antiviral Activity of a Silydianin-Rich Extract from Seeds Against Four Strains of Enteroviruses: EV71, Coxsackievirus B2, Coxsackievirus A10, and Poliovirus SL-1 and Its Impact on Improving Delayed Gastric Emptying in Mice.富含水飞蓟宾宁的种子提取物对四种肠道病毒株(肠道病毒71型、柯萨奇病毒B2型、柯萨奇病毒A10型和脊髓灰质炎病毒SL-1)的体外抗病毒活性及其对改善小鼠胃排空延迟的影响。
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