Revealing the efficacy-toxicity relationship of Fuzi in treating rheumatoid arthritis by systems pharmacology

Wuwen Feng,Cheng Peng,Dandan Zhang,Juan Liu,Yuzhu Tan,Hao Cheng

doi:10.1038/s41598-021-02167-5

Wuwen Feng, Cheng Peng + Show 4 more

Open Access

https://doi.org/10.1038/s41598-021-02167-5

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Abstract

In recent decades, herbal medicines have played more and more important roles in the healthcare system in the world because of the good efficacy. However, with the increasing use of herbal medicines, the toxicity induced by herbal medicines has become a global issue. Therefore, it is needed to investigate the mechanism behind the efficacy and toxicity of herbal medicines. In this study, using Aconiti Lateralis Radix Praeparata (Fuzi) as an example, we adopted a systems pharmacology approach to investigate the mechanism of Fuzi in treating rheumatoid arthritis and in inducing cardiac toxicity and neurotoxicity. The results showed that Fuzi has 25 bioactive compounds that act holistically on 61 targets and 27 pathways to treat rheumatoid arthritis, and modulation of inflammation state is one of the main mechanisms of Fuzi. In addition, the toxicity of Fuzi is linked to 32 compounds that act on 187 targets and 4 pathways, and the targets and pathways can directly modulate the flow of Na+, Ca2+, and K+. We also found out that non-toxic compounds such as myristic acid can act on targets of toxic compounds and therefore may influence the toxicity. The results not only reveal the efficacy and toxicity mechanism of Fuzi, but also add new concept for understanding the toxicity of herbal medicines, i.e., the compounds that are not directly toxic may influence the toxicity as well.

Highlights

In recent decades, herbal medicines have played more and more important roles in the healthcare system in the world because of the good efficacy
The results showed that 51 targets only contribute to the efficacy in treating rheumatoid arthritis, 189 targets are only responsible for the toxicity, and 10 targets are involved in both toxicity and efficacy of Fuzi
We found out that 25 bioactive compounds can act on 61 targets and 27 pathways to treat rheumatoid arthritis, and 32 bioactive compounds can act on 187 targets and 4 pathways to induce toxicity

Summary

Introduction

Herbal medicines have played more and more important roles in the healthcare system in the world because of the good efficacy. In this study, using Aconiti Lateralis Radix Praeparata (Fuzi) as an example, we adopted a systems pharmacology approach to investigate the mechanism of Fuzi in treating rheumatoid arthritis and in inducing cardiac toxicity and neurotoxicity. Except for the herbal medicines that contain aristolochic acids, there are many herbal medicines with strong toxicity that are still used in the clinic. Aconiti Lateralis Radix Praeparata (Fuzi) is the typical herbal medicine with conspicuous efficacy and strong toxicity. We adopted a standard systems pharmacology approach to screen the compounds that are responsible for the efficacy and toxicity of Fuzi in treating arthritis and inducing toxicity, respectively (Fig. 1). This work can be helpful for a comprehensive understanding of the efficacy-toxicity relationship of toxic herbal medicines in treating diseases

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Conclusion