Cresorol

Pinus sylvestris var. mongolica is a naturally susceptible host for the pine wood nematodes (PWNs, Bursaphelenchus xylophilus ) and a dominant afforestation tree species in northeastern China. With the continuous northward expansion of PWNs, P. sylvestris var. mongolica may become a critical conduit for their further expansion. To prevent pine wilt disease (PWD) from spreading via P. sylvestris var. mongolica in northeastern China, it is essential to elucidate its defense mechanisms against PWN and enhance its resistance.

Transcriptome analysis of P. sylvestris var. mongolica following inoculation with PWNs revealed the involvement of chalcone synthase ( chs ) genes in the flavonoid biosynthesis pathway, indicating their crucial role in the interaction between P. sylvestris var. mongolica and PWN. Treatment with elicitors known to induce chs gene expression—chitosan (CTS), chitosan oligosaccharide (COS), and sodium alginate (NaAlg)—delayed the progression of PWD, with NaAlg exhibiting the strongest protective effect. Differentially expressed genes (DEGs) enriched in the pathways related to flavonoid biosynthesis were observed following treatment with 100 mg/L NaAlg, and upregulated expressions of chs genes. This treatment also increased the abundance of key flavonoid pathway metabolites, including phloretin, chrysoeriol, and L‐tyrosine. However, inoculation with PWN following 100 mg/L NaAlg treatment downregulated expressions of chs genes and consumed phloretin, chrysoeriol, and L‐tyrosine, while promoting the accumulation of p‐coumaryl alcohol.

The expression of chs genes plays a critical role in the defense of P. sylvestris var. mongolica against PWN infection. Spraying 100 mg/L NaAlg solution before PWN infection activates chs genes in P. sylvestris var. mongolica , regulating the levels of L‐tyrosine, phloretin, chrysoeriol, and p‐coumaryl alcohol to enhance self‐resistance against PWN, thereby delaying the progression of PWD in P. sylvestris var. mongolica . © 2025 Society of Chemical Industry.

Lung cancer remains a major global health burden with high mortality rates and limited therapeutic options. Natural flavonoids, particularly those derived from Cassia species, have shown immunomodulatory and anticancer potential. This study investigates the therapeutic promise of selected Cassia-derived flavonoids targeting key lung cancer-associated proteins: Prostaglandin-endoperoxide synthase 2 (PTGS2), Mast/stem cell growth factor receptor (KIT), and Xanthine dehydrogenase (XDH).

Eight flavonoids were selected based on literature and database-reported bioactivity. Target prediction was performed using SwissTargetPrediction and STITCH, followed by pathway enrichment via STRING and KEGG databases. Molecular docking was conducted using AutoDock Vina against PTGS2 (PDB: 5IKQ), KIT (1N5X), and XDH (4U0I). Top-ranked complexes underwent 100 ns molecular dynamics (MD) simulations with GROMACS to assess binding stability, RMSD, and conformational behavior. Drug-likeness, ADME, and toxicity profiles were evaluated using SwissADME and ProTox-II. Standard drugs (Trametinib, Nivolumab, Erlotinib) were used for comparison.

Epicatechin and Hispidulin showed the strongest binding affinities with PTGS2 (−9.04 kcal/mol) and XDH (−8.22 kcal/mol), respectively, with stable RMSD profiles. Chrysoeriol demonstrated the highest binding to KIT (−8.68 kcal/mol), outperforming Nivolumab (−6.03 kcal/mol). All selected flavonoids displayed acceptable pharmacokinetic profiles and low predicted toxicity. MD simulations confirmed the dynamic stability of key complexes.

Cassia-derived flavonoids represent promising multi-target candidates for lung cancer therapy, particularly through modulation of PTGS2, KIT, and XDH. Their favorable interaction profiles and safety predictions warrant further experimental and in vivo validation.