Encapsulation of Aconitine in Self-Assembled Licorice Protein Nanoparticles Reduces the Toxicity In Vivo.

Li-jing Ke,Jian-wu Zhou,Ping-fan Rao,Yong Shen,Guan-zhen Gao

doi:10.1186/s11671-015-1155-1

Li-jing Ke, Jian-wu Zhou + Show 3 more

Open Access

https://doi.org/10.1186/s11671-015-1155-1

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Abstract

Many herbal medicines and compositions are clinically effective but challenged by its safety risks, i.e., aconitine (AC) from aconite species. The combined use of Radix glycyrrhizae (licorice) with Radix aconite L. effectively eliminates toxicity of the later while increasing efficacy. In this study, a boiling-stable 31-kDa protein (namely GP) was purified from licorice and self-assembled into nanoparticles (206.2 ± 2.0 nm) at pH 5.0, 25 °C. The aconitine-encapsulated GP nanoparticles (238.2 ± 1.2 nm) were prepared following the same procedure and tested for its toxicity by intraperitoneal injection on ICR mouse (n = 8). Injection of GP-AC nanoparticles and the mixed licorice-aconite decoction, respectively, caused mild recoverable toxic effects and no death, while the aconitine, particle-free GP-AC mixture and aconite decoction induced sever toxic effects and 100 % death. Encapsulation of poisonous alkaloids into self-assembled herbal protein nanoparticles contributes to toxicity attenuation of combined use of herbs, implying a prototype nanostructure and a universal principle for the safer clinical applications of herbal medicines.

Highlights

Aconitine (AC), known as devil’s helmet, is a highly poisonous alkaloid derived from various aconite species
It has been known that liquiritin from licorice forms complexation with aconitine and reduces the amount of free aconitine [7], indicating that interactions between aconitine with other major amphiphilic compounds from licorice may facilitate the formation of aconitine complex of such kind, too
Among which the protein with molecular weight around 31.0 kDa has the highest content and remained in the decoction of licorice. This protein was purified with anionic exchange liquid chromatography (High-Q), followed by hydrophobic liquid chromatography (POROS® R1), and named as the purified protein from licorice roots (GP)

Summary

Introduction

Aconitine (AC), known as devil’s helmet, is a highly poisonous alkaloid derived from various aconite species. Aconitine and its derivatives are the major effective and toxic compositions of a Chinese medicinal herb, lateral roots of Aconitum carmichaelii Debx (Radix aconite lateralis, Sichuan aconite root) [1, 2], and an Indian herbal medicine, roots of Aconitum heterophyllum Wall (Atis) [3]. As an essential measure for clinical practice of traditional Chinese medicine, it is recommended that the aconite roots shall be used together with roots of Glycyrrhiza uralensis Fisch (Radix glycyrrhizae, Gan-Cao, licorice root) to eliminate the toxicity and improve efficacy [5, 6]. It has been known that liquiritin from licorice forms complexation with aconitine and reduces the amount of free aconitine [7], indicating that interactions between aconitine with other major amphiphilic compounds (i.e., protein) from licorice may facilitate the formation of aconitine complex of such kind, too

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