State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China.
Key Laboratory of the Ministry of Education for Standardization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China.
Sci Rep. 2021 Nov 29;11(1):23083. doi: 10.1038/s41598-021-02167-5.
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, Ca, 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.
近几十年来，由于草药的良好疗效，草药在世界医疗保健系统中发挥了越来越重要的作用。然而，随着草药的使用越来越多，草药引起的毒性已成为一个全球性问题。因此，有必要研究草药功效和毒性背后的机制。在这项研究中，我们以乌头碱（附子）为例，采用系统药理学方法研究附子治疗类风湿关节炎和引起心脏毒性和神经毒性的机制。结果表明，附子有 25 种生物活性化合物，整体作用于 61 个靶点和 27 条通路来治疗类风湿关节炎，而调节炎症状态是附子的主要机制之一。此外，附子的毒性与 32 种化合物有关，这些化合物作用于 187 个靶点和 4 条通路，这些靶点和通路可以直接调节 Na、Ca 和 K 的流动。我们还发现，像肉豆蔻酸这样的无毒化合物可以作用于有毒化合物的靶点，因此可能会影响毒性。这些结果不仅揭示了附子的功效和毒性机制，还为理解草药的毒性增添了新概念，即并非直接有毒的化合物也可能影响毒性。
