Evaluation of Ganoderma lucidum Across Varieties and Growth Stages: Integrating Chromatographic Profiling,...

To address the lack of a comprehensive quality control system for Ganoderma lucidum, we developed an integrated evaluation strategy across four varieties and three growth stages. This system integrates the targeted screening of anti-benign prostatic hyperplasia (BPH) triterpenoids acting on 5α-reductase type 2 (SRD5A2) with a chemical consistency assessment utilizing systematic quantitative fingerprint method (SQFM) and chemometrics. UPLC-Q-TOF-MS/MS identified 85 triterpenoids in the samples. An orthogonal partial least squares (OPLS) regression was utilized to screen seven chromatographic peaks that positively correlated with SRD5A2 inhibitory activity. Three principal bioactives were structurally identified as ganoderic acids DM and B, and ganoderenic acid A, which demonstrated significant in vitro SRD5A2 inhibition rates of 61.16 ± 1.87%, 36.41 ± 1.10%, and 41.82 ± 2.09%, respectively. Molecular dynamics simulations and averaged weak interaction analysis revealed that these compounds exert potent enzyme inhibition via hydrogen bonds and hydrophobic interactions with distinct SRD5A2 amino acid residues. The SQFM-chemometrics quality system confirmed ten samples reached Grade 6 or above, identifying the H3 variety at the initial stage as possessing the highest active ingredient content and optimal overall quality. This integrated framework enables rapid bioactive discovery and robust standardization for G. lucidum-based functional foods, thereby facilitating their industrial development.