Through targeted isolation guided by feature-based molecular networking, nine previously undescribed β-acids, designated lupulxinones A-I (1-9), were obtained from the female inflorescences of hops (Humulus lupulus L.). Their structures were elucidated through comprehensive spectroscopic analysis, and the absolute configurations were established by electronic circular dichroism calculation together with X-ray single-crystal diffraction. Notably, lupulxinones A and B (1-2) are rare oxidized β-acids possessing a 5/5/6/5 tetracyclic scaffold with an embedded tetrahydrofuran ring that precludes enol interconversion. Additionally, lupulxinones A and B were separated into their respective enantiomers using a chiral chromatographic column. The biological evaluation revealed that compounds 3, 5, and 8 exhibited antibacterial activity against Cutibacterium acnes, with 8 displaying the most potent antiacne activity (MIC = 1.56 μg/mL; MBC = 3.13 μg/mL). Moreover, 1a and 3 showed moderate inhibition of LPS-induced nitric oxide production in RAW264.7 macrophages at 100 μM. Collectively, these findings suggest that hop extracts hold therapeutic promise for acne treatment.
Zou et al. (Tue,) studied this question.