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人参皂甙 Rh2 的活性通过与膜神经鞘磷脂的相互作用而增强，但被胆固醇抑制。

The activity of the saponin ginsenoside Rh2 is enhanced by the interaction with membrane sphingomyelin but depressed by cholesterol.

机构信息

Université catholique de Louvain, Louvain Drug Research Institute, Cellular & Molecular Pharmacology Unit, 1200, Brussels, Belgium.

Université catholique de Louvain, de Duve Institute, Cell Biology Unit, 1200, Brussels, Belgium.

出版信息

Sci Rep. 2019 May 13;9(1):7285. doi: 10.1038/s41598-019-43674-w.

DOI:10.1038/s41598-019-43674-w
PMID:31086211
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6513819/
Abstract

The membrane activity of some saponins, such as digitonin or alpha-hederin, is usually attributed to their interaction with membrane cholesterol (Chol). This contrasts with our recent publication showing that Chol, contrary to sphingomyelin (SM), can delay the cytotoxicity of the saponin ginsenoside Rh2, challenging the usual view that most saponins mediate their membrane effects through interaction with Chol. The aim of the present study was to elucidate the respective importance of Chol and SM as compared to phosphatidylcholine (PC) species in the membrane-related effects of Rh2. On simple lipid monolayers, Rh2 interacted more favorably with eggSM and DOPC than with Chol and eggPC. Using Large Unilamellar Vesicles (LUVs) of binary or ternary lipid compositions, we showed that Rh2 increased vesicle size, decreased membrane fluidity and induced membrane permeability with the following preference: eggSM:eggPC > eggSM:eggPC:Chol > eggPC:Chol. On Giant Unilamellar Vesicles (GUVs), we evidenced that Rh2 generated positive curvatures in eggSM-containing GUVs and small buds followed by intra-luminal vesicles in eggSM-free GUVs. Altogether, our data indicate that eggSM promotes and accelerates membrane-related effects induced by Rh2 whereas Chol slows down and depresses these effects. This study reconsiders the theory that Chol is the only responsible for the activity of saponins.

摘要

一些皂苷的膜活性，如地奥明或α-常春藤苷，通常归因于它们与膜胆固醇（Chol）的相互作用。这与我们最近的出版物形成对比，该出版物表明，与鞘磷脂（SM）相反，Chol 可以延迟皂苷人参皂苷 Rh2 的细胞毒性，这挑战了大多数皂苷通过与 Chol 相互作用来介导其膜效应的常见观点。本研究的目的是阐明 Chol 和 SM 与磷脂酰胆碱（PC）相比在 Rh2 的膜相关效应中的相对重要性。在简单的脂质单层上，Rh2 与蛋黄 SM 和 DOPC 的相互作用优于与 Chol 和蛋黄 PC 的相互作用。使用二元或三元脂质组成的大单层囊泡（LUVs），我们表明 Rh2 增加了囊泡大小，降低了膜流动性并诱导了膜通透性，其偏好顺序为：蛋黄 SM：蛋黄 PC>蛋黄 SM：蛋黄 PC：Chol>蛋黄 PC：Chol。在巨单层囊泡（GUVs）上，我们证明 Rh2 在含有蛋黄 SM 的 GUVs 中产生正曲率，并在蛋黄 SM 无 GUVs 中产生小芽和随后的腔内囊泡。总的来说，我们的数据表明蛋黄 SM 促进和加速了 Rh2 诱导的膜相关效应，而 Chol 则减缓和抑制了这些效应。这项研究重新考虑了 Chol 是唯一负责皂苷活性的理论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edb/6513819/959d101a81c6/41598_2019_43674_Fig11_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edb/6513819/09d8cffc983b/41598_2019_43674_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edb/6513819/19d03ebdf886/41598_2019_43674_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edb/6513819/e1973b91ed82/41598_2019_43674_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edb/6513819/50b013136256/41598_2019_43674_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edb/6513819/8209e5ef69fe/41598_2019_43674_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edb/6513819/c378e89e1c8f/41598_2019_43674_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edb/6513819/0dd06177b94f/41598_2019_43674_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edb/6513819/75228546a063/41598_2019_43674_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edb/6513819/25dc8359266a/41598_2019_43674_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edb/6513819/5bc3cbab571c/41598_2019_43674_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4edb/6513819/959d101a81c6/41598_2019_43674_Fig11_HTML.jpg

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