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Yinhuo Tang alleviates ionizing radiation injury via modulating PI3K-Akt signaling and metabolomics in mice.

Yu-yan Li,Dan Lu,Lihui Zhou,Yingxin Zhang,Chaofeng Yang,Siyu Liu,Xinze Zhang,Mojiao Zhao,Yong Yang

Published 2025 in Journal of Ethnopharmacology

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE Irradiation injury happens in daily life as ionizing radiation (IR) develops, which can spread through tissues and organs, causing many diseases. Yinhuo Tang (YHT/YH), a traditional Chinese medicine formula, is used to alleviate "yin deficiency with excessive heat," whose symptoms are similar to those induced by ionizing radiation (IR). AIM OF THE STUDY This study aims to determine the prophylactic protective effect of YHT on IR injury in a pretreatment mouse model and explore the underlying mechanisms involved. MATERIALS AND METHODS The preventive effect of YHT on IR is investigated using a radiation injury mouse model with 14 days pre-administration. An untargeted metabolomics analysis was conducted to assess YHT-mediated metabolic changes and identify key pathways affected. UPLC-Q/TOF-MS characterized chemical constituents and serum ingredients of YHT. Network pharmacology, based on the serum components, was used to predict the key drug-disease targets. Molecular docking was performed to predict interactions between core targets and the active ingredients of YHT. Proteomics and Western blot were conducted to reveal the potential mechanisms by which YHT affects IR injury. RESULTS YHT reduced cellular oxidative damage, promoted hematopoietic regeneration and immunoprotection, and enhanced genomic stability and mitotic fidelity after radiation exposure. Metabolomics revealed that YHT provides a protective effect by modulating metabolites, particularly in the linoleic acid metabolic pathway. UPLC-Q/TOF-MS analysis detected specific chemical compounds in YHT. Combining serum-based network pharmacology and proteomics revealed that YHT protects against IR injury in mouse models through multiple proteins and pathways, including the suppression of phosphoinositide-3-kinase/protein kinase B (PI3K-Akt) signaling. CONCLUSIONS Our finding suggests that YHT prophylactically alleviates IR injury by modulating physiological processes, including antioxidative responses, cell regeneration, linoleic acid metabolism, and PI3K-Akt signaling. YHT may be a promising traditional Chinese medicine for reducing radiation-induced injury.

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