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丹酚酸B对人类严重病原体脑膜炎奈瑟菌的新型抗感染潜力。

Novel anti-infective potential of salvianolic acid B against human serious pathogen Neisseria meningitidis.

作者信息

Huttunen Sanna, Toivanen Marko, Liu Chenghai, Tikkanen-Kaukanen Carina

机构信息

School of Pharmacy, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.

出版信息

BMC Res Notes. 2016 Jan 13;9:25. doi: 10.1186/s13104-016-1838-4.

Abstract

BACKGROUND

Epidemics of meningococcal meningitis cause significant health problems especially in Sub-Saharan Africa. Novel anti-infective candidates are needed. In modern anti-adhesion therapy initial attachment of bacteria to host cells is prevented. Our unique studies have revealed anti-adhesive candidates from natural products, namely milk and berries, against Neisseria meningitidis adhesion. In the present study against N. meningitidis adhesion, a novel binding inhibitor was found; salvianolic acid B (SA-B), a polyphenol from the radix Salviae miltiorrhizae, an important part of Chinese folk medicine.

METHODS

In order to test inhibition of meningococcal pili binding and anti-adhesion activity of SA-B, bovine thyroglobulin, a reference glycoprotein for meningococcal receptor was used in a microtiter plate assay. Inhibitory activity was tested by using serial dilutions of SA-B extracts of 98 and 70% purity. Results were confirmed in a HEC-1B cell dot assay and antimicrobial activity was measured by using a microbroth dilution assay.

RESULTS

Almost total (93%) inhibition of pili binding, anti-adhesion, was achieved with the 70% extract of SA-B at the concentration of 0.3 mg/mL in the bovine thyroglobulin reference model. 50% binding inhibition activity was achieved with 0.6 µg/mL of the SA-B extract. Total inhibition of the pili binding to HEC-1B cells was found at the tested concentration of 0.5 mg/mL. The 98% pure SA-B resulted in weaker inhibition. At the concentration of 0.3 mg/mL 78% inhibition was achieved in the thyroglobulin model. For 50% inhibition 2.4 μg/mL of pure SA-B was needed. The difference between the binding inhibition activities (70 and 98% pure SA-B) was statistically significant (P = 0.03). Antimicrobial activity of 70% SA-B, when investigated against N. meningitidis, was detected only in relatively high concentrations.

CONCLUSIONS

Our results indicate that plant SA-B may prevent meningococcal infections by inhibiting meningococcal binding and may thus have an impact on the amount of nasopharyngeal carriers of N. meningitidis. This may prevent the spreading of meningococcal infections between humans. One could conclude that SA-B and its source dried radix S. miltiorrhizae, which is an important part of Chinese folk medicine, could be valuable candidates for further research in meningococcal disease prevention.

摘要

背景

脑膜炎球菌性脑膜炎的流行引发了严重的健康问题,尤其是在撒哈拉以南非洲地区。因此需要新型抗感染候选药物。现代抗黏附疗法旨在阻止细菌最初附着于宿主细胞。我们独特的研究已从天然产物(即牛奶和浆果)中发现了针对脑膜炎奈瑟菌黏附的抗黏附候选物。在本项针对脑膜炎奈瑟菌黏附的研究中,发现了一种新型结合抑制剂;丹酚酸B(SA - B),一种来自丹参根的多酚,丹参是中国民间医学的重要组成部分。

方法

为了测试SA - B对脑膜炎球菌菌毛结合的抑制作用及其抗黏附活性,在微量滴定板试验中使用了牛甲状腺球蛋白,一种脑膜炎球菌受体的参考糖蛋白。通过使用纯度为98%和70%的SA - B提取物的系列稀释液来测试抑制活性。在HEC - 1B细胞斑点试验中对结果进行了确认,并通过微量肉汤稀释试验测量了抗菌活性。

结果

在牛甲状腺球蛋白参考模型中,浓度为0.3 mg/mL的70% SA - B提取物几乎完全(93%)抑制了菌毛结合及抗黏附作用。0.6 μg/mL的SA - B提取物实现了50%的结合抑制活性。在0.5 mg/mL的测试浓度下发现菌毛与HEC - 1B细胞的结合被完全抑制。98%纯度的SA - B产生的抑制作用较弱。在甲状腺球蛋白模型中,浓度为0.3 mg/mL时实现了78%的抑制。对于50%的抑制,需要2.4 μg/mL的纯SA - B。两种纯度(70%和98%)的SA - B之间的结合抑制活性差异具有统计学意义(P = 0.03)。当针对脑膜炎奈瑟菌进行研究时,仅在相对高浓度下检测到70% SA - B的抗菌活性。

结论

我们的结果表明,植物SA - B可能通过抑制脑膜炎球菌的结合来预防脑膜炎球菌感染,因此可能对脑膜炎奈瑟菌鼻咽部带菌者数量产生影响。这可能会阻止脑膜炎球菌感染在人与人之间传播。可以得出结论,SA - B及其来源丹参干燥根(中国民间医学的重要组成部分)可能是预防脑膜炎球菌病进一步研究的有价值候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a874/4710984/ba07da4931ed/13104_2016_1838_Fig1_HTML.jpg

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