Therapeutic effects and mechanisms of Inonotus hispidus extract and active monomer compounds in a rat mammary gland hyperplasia model

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.