Natural Small-Molecule-Based Carrier-Free Self-Assembly Library Originated from Traditional Chinese Herbal Medicine

Abstract

The carrier-free self-assembly of small molecules opens a new window for the development of nanomaterials. This study is dedicated to developing binary small-molecular self-assemblies derived from phytochemicals in traditional Chinese herbal medicine. Among them, Rhei Radix et Rhizoma and Coptidis Rhizoma are a common pair used in clinics for thousands of years. Here, we found that there were numerous spherical supramolecular nanoparticles (NPs) originated from Rhei Radix et Rhizoma and Coptidis Rhizoma decoction. Ultra-performance liquid chromatography/ tandem mass spectrometry (UPLC-MS/MS) was used to analyze the composition of the supramolecules, and a total of 119 phytochemicals were identified (23 anthraquinones, 31 alkaloids, 24 organic acids, 8 tannins, and other components). Isothermal titration calorimetry (ITC) showed that the interaction between Rhei Radix et Rhizoma and Coptidis Rhizoma was a spontaneous exothermic reaction, indicating that their phytochemicals had the property of self-assembly and interacted to form supramolecules in the decocting process. Furthermore, scanning electron microscopy (SEM), UV, IR, NMR, and ITC were used to verify that rhein and coptisine could self-assemble into nanofibers (Rhe-Cop NFs), while emodin and coptisine could self-assemble into nanoparticles (Emo-Cop NPs). The formation mechanism analysis of the self-assemblies revealed that they were induced by electrostatic attraction, hydrogen bonding, and π−π stacking, forming nanospheres of about 50 nm and nanofibers. The current study not only provides an idea of discovering carrier-free self-assemblies from traditional herbal medicine decoction but also supplies a reference for the design of binary self-assembly of small molecules in the future.

Insights into the Mechanism of Supramolecular Self-Assembly in the Astragalus membranaceus–Angelica sinensis Codecoction

“…Further, the irregular spherical shape of AA-NPs was also observed in the TEM image (Figure B). In the UV–vis absorption spectrum, a broad peak at 256 nm of AA-NPs was attributed to the π–π* transition of carbon, suggesting the presence of the benzene ring or CC (Figure C) . Interestingly, AA-NPs also possessed a certain fluorescence.…”

“…Modern research on herb decoctions should clarify the characteristics of each component and the interaction between them. Gradually, an increasing number of researchers have found that nanoscale particles are ubiquitous in decoctions, which are associated with their pharmacological effects . For example, a colloid system with a size of 162 nm isolated from the codecoction of Glycyrrhiza uralensis Fisch and Coptis chinensis Franch was composed of 34 flavonoids, 34 alkaloids, and 2 triterpenoids, showing stronger antibacterial activity than a noncolloidal solution .…”

“…The resulting data also indicated that aggregates and precipitates in herbal decoctions should be carefully handled in production and pharmacological research. In addition, nanoparticles discovered in Huanglian Jiedu , Huanglian , Maxing Shigan , Baihu , Liujunzi , and Shaoyao Gancao decoctions showed superior properties and activities. ,, Even in Turkish gall extracts, researchers found the presence of spherical nanoparticles that possessed the ideal size, strong antioxidant activity in scavenging various radicals, and antibacterial performance . However, whether nanoparticles exist in the AM–AS codecoction remains unclear.…”

“…However, whether nanoparticles exist in the AM–AS codecoction remains unclear. Most of these nanoparticles with sizes in the range of 100–600 nm had strong stability and high bioavailability . Through ultrahigh-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HR-MS) analysis, it was found that the chemical compositions of nanoparticles in decoctions were extremely complex, including saponins, polysaccharides, flavonoids, and alkaloids .…”

Nanostructures in Chinese herbal medicines (CHMs) for potential therapy

“…37,38 Similar results are reported for rhein and coptisine (Rhe-Cop) nanofibers and emodin and coptisine (Emo-Cop) nanoparticles, which form through electrostatic attraction, hydrogen bonding, and p-p stacking. 39 BBR and aristolochic acid can also self-assemble into linear heterogenous supramolecules through electrostatic attraction and p-p stacking, which decreases the toxicity of aristolochic acidinduced acute kidney injury. 40 Single components of CHMs also undergo self-assembly.…”