Review of Modern Research on Toxicity of Traditional Chinese Medicine Aconm Lateralis Radix Praeparaia

The traditional Chinese medicine Aconm Lateralis Radix Praeparaia(Fuzi)is pungent and sweet in taste,hot in nature,and has high toxicity.It governs the meridians of the heart,kidney and spleen.It has the functions of restoring yang to save from collapse,dispersing cold and removing dampness,and warming the middle to relieve pain.It is often used for the treatment of yang collapse,cold limbs,weak pulse,heart yang deficiency,heart pain due to chest impediment,abdominal cold-pain,kidney yang deficiency,impotence and cold in womb,and syndrome of exogenous disease due to yang deficiency,etc.Its great yang qi and strong medicinal properties often bring about toxic and adverse effects.However,after processing or combination with other medicinal materials,the effects of Aconm Lateralis Radix Praeparaia are quite different.Not only the toxicity is greatly reduced,but also the curative effects are strengthened.Through searching related literature,this paper reviewed the researches about the toxicity reduction and curative effect improvement of Aconm Lateralis Radix Praeparaia,in order to provide a certain theoretic reference for future further research of Aconm Lateralis Radix Praeparaia.

附子甘草配伍减毒增效作用机制研究进展及展望

附子—甘草为中医常用药对,也是中药七情"相畏相杀"配伍规律之典范,近年来药学工作者对其作用机制研究较多。本文通过文献查阅,综述了近年来该药对的研究进展,并在此基础上结合中医药理论,提出了一些新的研究思路,为进一步研究和开发利用提供参考。

Study on the compatibility principle of Wutou Decoction based on network pharmacology

Objective To investigate the underlying drug enhancement mechanisms of the Chuanwu(Aconiti Radix)and Huangqi(Astragali Radix)combination and toxicity reduction of Chuan-wu combined with Gancao(Glycyrrhizae Radix et Rhizoma)in Wutou Decoction(乌头汤,WTD),and to elucidate the compatibility principle.Methods The active compounds and potential effective targets of the selected combinations were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicines Integrated Database(TCMID).The toxicity of Chuanwu(Aconiti Radix)was investigated by selecting all five toxic compounds from the literature and the TCMSP database,and obtaining their targets through SwissTargetPrediction.Targets related to rheumatoid arthritis(RA)were searched using Dis-GeNET,GenCards,and Online Mendelian Inheritance in Man(OMIM).Mutual targets between the drug pairs and RA were selected as potential RA therapy targets.The medicinally active compound-target network was constructed using Cytoscape 3.9.0.Gene ontology(GO)term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrich-ment were performed using the Database for Annotation,Visualization,and Integrated Dis-covery(DAVID)platform.Results We obtained 191 active compound targets for Gancao(Glycyrrhizae Radix et Rhizoma),171 for Huangqi(Astragali Radix),and 103 for Chuanwu(Radix Aconiti)(hypo-aconitine’s target was obtained through literature and SwissTargetPrediction).A total of 5872 genes were obtained for RA.A drug-active compound-target network involving 13 effect-en-hancing and nine toxicity reduction targets was constructed.PGR was the main effect en-hancement target,and KCNH2 was the main toxicity reduction target.The effect-enhancing targets were related to 23 GO terms(such as positive regulation of transcription from RNA polymerase II promoter,steroid hormone-mediated signaling pathway,plasma membrane,and protein binding)(P<0.01),and 13 KEGG pathways related to synergism[such as estro-gen signaling pathway,cholinergic synapse,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway].The toxicity reduction targets were related to 28 GO terms(mainly involes G-protein coupled receptor signaling pathway,plasma membrane,and drug binding)(P<0.01),and five KEGG pathways related to toxicity reduction(cholinergic syn-apse,calcium signaling pathway,regulation of actin cytoskeleton,neuroactive ligand-recept-or interaction,and serotonergic synapse).Conclusion The combination of Chuanwu(Aconiti Radix)and Huangqi(Astragali Radix)plays an important effect-enhancing role in WTD and involves the estrogen and PI3K/Akt sig-naling pathways,with PGR as the core.The Chuanwu(Aconiti Radix)and Gancao(Gly-cyrrhizae Radix et Rhizoma)combination decreases toxicity in WTD and is associated with the cholinergic synapse and calcium signaling pathways,with KCNH2 as the core.