Cresorol

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.

Chrysoeriol, a flavonoid naturally found in several plants, including Danggui Susan, a traditional herbal medicine, exhibits promising anti-inflammatory and antioxidant properties. Its potential to prevent cardiovascular diseases, primarily through inhibiting platelet activation and aggregation, has attracted significant interest. This study aimed to investigate the molecular mechanisms underlying the antiplatelet effects of chrysoeriol. The compound effectively suppressed collagen-induced platelet aggregation without inducing cytotoxicity. Chrysoeriol elevated intracellular levels of cyclic AMP (cAMP) and cyclic GMP (cGMP), enhanced inositol 1,4,5-trisphosphate receptor (IP₃R) phosphorylation, and reduced cytosolic calcium (Ca²⁺) mobilization, all of which contributed to its antiplatelet action. Furthermore, chrysoeriol inhibited the phosphorylation of PI3K, Akt, JNK, and p38 MAPK, pathways involved in the activation of cytosolic phospholipase A2 (cPLA₂) and thromboxane A2 (TXA₂) production. These effects were accompanied by reduced TXA₂ production and secretion of dense granules (ATP and serotonin). Chrysoeriol also impaired thrombin-induced clot retraction, further suggesting its capacity to regulate platelet responses and cytoskeletal rearrangements. These findings highlight chrysoeriol's multi-target mechanisms, including modulation of cyclic nucleotides, kinase pathways, and platelet function, offering potential as a therapeutic agent to prevent thrombotic cardiovascular events.