State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Beijing, 100005, China.
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biophysics and Structural Biology, Peking Union Medical College, Beijing, 100005, China.
Sci China Life Sci. 2019 Mar;62(3):333-348. doi: 10.1007/s11427-018-9508-0. Epub 2019 Mar 21.
Traditionally, herbal medicine is consumed by drinking decoctions produced by boiling herbs with water. The functional components of the decoction are heat stable. Small RNAs (sRNAs) were reported as a new class of functional components in decoctions. However, the mechanisms by which sRNAs survive heat treatment of the decoction and enter cells are unclear. Previous studies showed that plant-derived exosome-like nanoparticles (ELNs), which we call botanosomes, could deliver therapeutic reagents in vivo. Here, we report that heat-stable decoctosomes (ELNs) from decoctions have more therapeutic effects than the decoctions in vitro and demonstrate therapeutic efficacy in vivo. Furthermore, sRNAs, such as HJT-sRNA-m7 and PGY-sRNA-6, in the decoctosome exhibit potent anti-fibrosis and anti-inflammatory effects, respectively. Decoctosome is comprised of lipids, chemical compounds, proteins, and sRNAs. A medical decoctosome mimic is called bencaosome. A single lipid sphinganine (d22:0) identified in the decoctosome was mixed and heated with the synthesized sRNAs to form the simplest bencaosome. This simple bencaosome structure was identified by critical micelle concentration (cmc) assay that sRNAs coassembled with sphinganine (d22:0) to form the lipid layers of vesicles. The heating process facilitates co-assembly of sRNAs and sphinganine (d22:0) until a steady state is reached. The artificially produced sphinganine-HJT-sRNA-m7 and sphinganine- PGY-sRNA-6 bencaosomes could ameliorate bleomycin-induced lung fibrosis and poly(I:C)-induced lung inflammation, respectively, following oral administration in mice. Our study not only demonstrates that the herbal decoctosome may represent a combinatory remedy in precision medicine but also provides an effective oral delivery route for nucleic acid therapy.
传统上，草药是通过用水煮沸草药来饮用汤剂来服用的。汤剂的功能成分是热稳定的。小 RNA（sRNA）被报道为汤剂中的一类新的功能成分。然而，sRNA 如何在汤剂的热处理下存活并进入细胞的机制尚不清楚。先前的研究表明，植物来源的外泌体样纳米颗粒（ELN），我们称之为 botanosomes，可以在体内递送电疗试剂。在这里，我们报告说，来自汤剂的热稳定的 decoctosomes（ELN）在体外比汤剂具有更好的治疗效果，并在体内证明了治疗效果。此外，在 decoctosome 中的 sRNA，如 HJT-sRNA-m7 和 PGY-sRNA-6，分别表现出强大的抗纤维化和抗炎作用。Decoctosome 由脂质、化合物、蛋白质和 sRNA 组成。汤剂的模拟物称为 bencaosome。在 decoctosome 中鉴定的单一脂质神经酰胺（d22:0）与合成的 sRNA 混合并加热，形成最简单的 bencaosome。通过临界胶束浓度（cmc）测定鉴定了这种简单的 bencaosome 结构，sRNA 与神经酰胺（d22:0）共同组装形成囊泡的脂质层。加热过程促进 sRNA 和神经酰胺（d22:0）的共同组装，直到达到稳定状态。人工产生的神经酰胺-HJT-sRNA-m7 和神经酰胺-PGY-sRNA-6 bencaosomes 可以改善博来霉素诱导的肺纤维化和 poly（I:C）诱导的肺炎症，分别在小鼠口服后。我们的研究不仅表明草药 decoctosome 可能代表精准医学中的组合疗法，而且为核酸治疗提供了一种有效的口服递送途径。
