Study on the underlying mechanism of Huachansu Capsule induced cardiotoxicity of normal rat by integrating transcriptomics, metabolomics and network toxicology.
J Ethnopharmacol
; 336: 118751, 2025 Jan 10.
Article
em En
| MEDLINE
| ID: mdl-39214192
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE Huachansu Capsule (HCSc) is a simple enteric-coated capsule refined from the skin of the dried toad, a traditional medicinal herb. It has been used clinically for many years to treat a variety of malignant tumors with remarkable efficacy. To date, a number of main components of HCSc have been reported to be cardiotoxic, but the specific mechanism of cardiotoxicity is still unknown. AIM OF THE STUDY The aim of this study was to elucidate the possible cardiotoxic symptoms caused by high-doses of HCSc and to further reveal the complex mechanisms by which it causes cardiotoxicity. MATERIALS AND METHODS:
UPLC-Q-Exactive Orbitrap MS and network toxicology were used to identify and predict the potential toxic components, related signaling pathways. Then, we used acute and sub-acute toxicity experiments to reveal the apparent phenomenon of HCSc-induced cardiotoxicity. Finally, we combined transcriptomics and metabolomics to elucidate the potential mechanism of action, and verified the putative mechanism by molecular docking, RT-qPCR, and Western blot.RESULTS:
We found 8 toad bufadienolides components may be induced cardiac toxicity HCSc main toxic components. Through toxicity experiments, we found that high dose of HCSc could increase a variety of blood routine indexes, five cardiac enzymes, heart failure indexes (BNP), troponin (cTnI and cTnT), heart rate and the degree of heart tissue damage, while low-dose of HCSc had no such changes. In addition, by molecular docking, found that 8 kinds of main toxic components and cAMP, AMPK, IL1ß, mTOR all can be a very good combination, especially in the cAMP. Meanwhile, RT-qPCR and Western blot results showed that HCSc could induce cardiotoxicity by regulating a variety of heart-related differential genes and activating the cAMP signaling pathway.CONCLUSIONS:
In this study, network toxicology, transcriptomics and metabolomics were used to elucidate the complex mechanism of possible cardiotoxicity induced by high-dose HCSc. Animal experiments, molecular docking, Western blot and RT-qPCR experiments were also used to verify the above mechanism. These findings will inform further mechanistic studies and provide theoretical support for its safe clinical application.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metabolômica
/
Transcriptoma
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Cardiotoxicidade
Limite:
Animals
Idioma:
En
Revista:
J Ethnopharmacol
Ano de publicação:
2025
Tipo de documento:
Article
País de publicação:
Irlanda