Glaucocalyxin A

To investigate the therapeutic effects of Chinese medicine Weifuchun (WFC, ) on gastric fundic gland polyps (FGPs).

FGPs organoids were constructed with patients-derived samples. The morphology and size of FGPs organoids were detected using bright-field imaging. Effective components and corresponding potential targets of WFC were screened using multiple open-source databases and research on Traditional Chinese Medicine or compound formulas. Core genes were identified through protein-protein interaction networks. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses of the core genes were conducted. The interactions between main components and core targets were analyzed through the FerrDb database. The expressions of core targets were detected by quantitative real-time polymerase chain reaction (qRT-PCR).

After WFC treatment, the number and size of FGPs organoids were significantly reduced. Twenty nine active drug components and 162 candidate targets of WFC for treating FGPs were identified, including 37 targets related to ferroptosis. Quercetin, Glaucocalyxin B, Melissoidesin U, Melissoidesin O, Hesperetin, Glaucocalyxin A, Angustifolin, Melissoidesin M, Di-n-octyl phthalate, and beta-sitosterol were identified as the main active compounds. SRC proto-oncogene, non-receptor tyrosine kinase, signal transducer and activator of transcription 3, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta, phosphoinositide-3-kinase regulatory subunit 1, and AKT serine/threonine kinase 1 were identified as the primary targets. KEGG pathways related to carcinogenesis, cell proliferation and metabolism, and oxidative stress. WFC promoted FGPs organoids' death and could be reversed by ferroptosis inhibitor of Erastin. The qRT-PCR results showed that WFC treatment could regulate the mRNA expression levels of solute carrier family 7 member 11, acyl-CoA synthetase long chain family member 4, and arachidonate 15-lipoxygenase, type B.

WFC may exert its therapeutic effects by inducing ferroptosis in FGPs cells.

To discover novel antimicrobial drug, 22 novel acylated derivatives were synthesized by A-ring modification of glaucocalyxin A. The structures of these derivatives were confirmed by NMR and MS data. In vitro antimicrobial activity of these compounds was evaluated against E. faecium, E. faecalis, MRSA, E. coli, A. baumannii and K. pneumoniae. The results showed compound 3d against E. faecium, E. faecalis and MRSA with a minimum inhibitory concentration of 4 μg/ml. And further molecular docking revealed that compound 3d has a higher binding affinity. In conclusion, compound 3d has the potential to develop into a new drug against drug-resistant bacteria.