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水苏碱 E2-a 对感染细粒棘球蚴原头蚴的实验小鼠的治疗和免疫调节作用。

Therapeutic and immunoregulatory effects of water-soluble alkaloids E2-a from Sophora moorcroftiana seeds as a novel potential agent against echinococcosis in experimentally protoscolex-infected mice.

机构信息

Department of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.

Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.

出版信息

Vet Res. 2018 Oct 4;49(1):100. doi: 10.1186/s13567-018-0596-9.

Abstract

Novel compounds and more efficient treatment options are urgently needed for the treatment of cystic echinococcosis (CE), which is caused by Echinococcus granulosus. The decoction of Sophora moorcroftiana (Fabaceae) has been used to treat parasitosis for years in traditional Tibetan medicine. The aim of this study was to screen insecticidal water-soluble alkaloids from S. moorcroftiana seeds and evaluate the therapeutic effects against CE and the immune response induced by the alkaloidal fraction. Low polarity compounds (E2-a) were isolated from water-soluble alkaloid (E2) and matrine and sophocarpine were identified as major components. The E2-a fraction was more effective against protoscoleces than other constituents from S. moorcroftiana. After 20 weeks of secondary infection with protoscoleces, mice were orally treated with E2-a (100 mg/kg/day) for 6 weeks to evaluate therapeutic and immunoregulatory activities. Compared with the untreated group, E2-a treatment induced a significant reduction in cyst weight (mean 2.93 g) (p < 0.05) and an impaired ultrastructural modification of the cyst. Interestingly, the application of E2-a resulted in a significant increased frequency of CD3CD4 T-cell subsets and decreased frequency of CD3PD-1 T-cell subsets, compared with protoscolece-infected mice without treatment. The E2-a fraction of S. moorcroftiana can inhibit the cyst development of CE and boost the specific immune response by reducing the expression of PD-1 and accelerate the cytokine secretion of antigen-specific T-cells. All data suggest the E2-a fraction from S. moorcroftiana seeds may be used as a new potential therapeutic option against E. granulosus infection.

摘要

新型化合物和更有效的治疗方法迫切需要治疗由细粒棘球蚴(Echinococcus granulosus)引起的包虫病(CE)。苦参(Fabaceae)的煎剂已在传统藏药中用于治疗寄生虫病多年。本研究旨在从苦参种子中筛选杀虫水溶性生物碱,并评估其对 CE 的治疗效果和生物碱部分诱导的免疫反应。从水溶性生物碱(E2)和苦参碱和氧化苦参碱中分离出低极性化合物(E2-a),并鉴定为主要成分。E2-a 馏分对原头蚴的活性比苦参的其他成分更有效。在二次感染原头蚴 20 周后,用 E2-a(100mg/kg/天)口服治疗 6 周,以评估治疗和免疫调节活性。与未治疗组相比,E2-a 治疗可显著降低囊肿重量(平均 2.93g)(p<0.05)并破坏囊肿的超微结构修饰。有趣的是,与未经治疗的原头蚴感染小鼠相比,E2-a 的应用导致 CD3CD4 T 细胞亚群的频率显著增加,而 CD3PD-1 T 细胞亚群的频率降低。与未经治疗的原头蚴感染小鼠相比,苦参的 E2-a 馏分可通过降低 PD-1 的表达抑制 CE 囊肿的发展并增强特异性免疫反应,并加速抗原特异性 T 细胞的细胞因子分泌。所有数据均表明,苦参种子的 E2-a 馏分可能被用作针对棘球蚴感染的新的潜在治疗选择。

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