Key Laboratory of Edible Fungi Resources and Utilization, Ministry of Agriculture and Rural Affairs, Jilin Agricultural University, No.2888 Xincheng Street, Nanguan District, Changchun, Jilin, 130118, China; College of Chinese Medicine Materials, Jilin Agricultural University, Changchun, 130118, China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 2):117274. doi: 10.1016/j.jep.2023.117274. Epub 2023 Oct 4.
Inonotus hispidus is the traditional Chinese medicine Sanghuang. Since ancient times, Sanghuang has been documented to be used in the treatment of female breast diseases. However, the pharmacological mechanism of Sanghuang in the treatment of mammary gland hyperplasia (HMG) remains unclear.
The ethyl acetate extract of the aging fruiting body of I. hispidus (IEAE) was used to study the pharmacological mechanism of IEAE in the treatment of HMG using non-targeted metabolomics.
The HMG rat model was established, and serum metabolomics was used to study the potential therapeutic mechanism of IEAE for HMG.
IEAE has obvious therapeutic effect on HMG model rats, and no obvious adverse reactions were observed. Non-targeted metabolomics showed that after IEAE intervention, the upstream metabolite D-erythrose 4-phosphate was significantly downregulated, aromatic amino acids such as tryptophan, tyrosine, and phenylalanine were downregulated, and the downstream metabolites N-acetyl-L-glutamate and L-proline were significantly upregulated. After an intervention with yakuchinone A, non-targeted metabolomics analyses demonstrated that yakuchinone A restored tetrahydrocorticosterone, cortisol, and etiocholanolone to normal levels, estriol was significantly upregulated, and steroid hormone biosynthesis was significantly activated.
IEAE was shown to have a good therapeutic effect on HMG in a rat model without adverse reactions. The mechanism of action was mainly based on the biosynthesis of amino acids. Small molecule metabolites such as D-erythrose 4-phosphate, N-acetyl-L-glutamate, and L-proline may be potential targets for IEAE in the treatment of HMG. Yakuchinone A is one of the main active components of IEAE, and plays a role by promoting the steroid hormone biosynthesis pathway. Estriol may be a potential target for the treatment of HMG with yakuchinone A, providing a new concept for clinical treatment of HMG.
裂蹄木层孔菌是中国传统医学桑黄。自古以来，桑黄就被记载用于治疗女性乳房疾病。然而，桑黄治疗乳腺增生（HMG）的药理机制尚不清楚。
采用裂蹄木层孔菌老化子实体的乙酸乙酯提取物（IEAE），采用非靶向代谢组学研究 IEAE 治疗 HMG 的药理机制。
建立 HMG 大鼠模型，采用血清代谢组学研究 IEAE 治疗 HMG 的潜在治疗机制。
IEAE 对 HMG 模型大鼠有明显的治疗作用，未见明显不良反应。非靶向代谢组学表明，IEAE 干预后，上游代谢物 D-赤藓糖 4-磷酸显著下调，色氨酸、酪氨酸和苯丙氨酸等芳香族氨基酸下调，下游代谢物 N-乙酰-L-谷氨酸和 L-脯氨酸显著上调。干预 yakuchinone A 后，非靶向代谢组学分析表明 yakuchinone A 将四氢皮质酮、皮质醇和表雄酮恢复正常水平，雌三醇显著上调，类固醇激素生物合成明显激活。
IEAE 对 HMG 大鼠模型无不良反应，具有良好的治疗作用。作用机制主要基于氨基酸的生物合成。D-赤藓糖 4-磷酸、N-乙酰-L-谷氨酸和 L-脯氨酸等小分子代谢物可能是 IEAE 治疗 HMG 的潜在靶点。Yakuchinone A 是 IEAE 的主要活性成分之一，通过促进类固醇激素生物合成途径发挥作用。雌三醇可能是 yakuchinone A 治疗 HMG 的潜在靶点，为临床治疗 HMG 提供了新的概念。
