臼杵 豊展

BACKGROUND: Gynostemma pentaphyllum (Thunb.), a traditional adaptogenic herb, is known for its bioactive components with potential anti-cancer properties. Acute myeloid leukemia (AML) progression is significantly influenced by Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3) signaling, while Wilms' tumor 1 (WT1) serves as a key prognostic marker. This study investigates the anti-leukemia activities of active G. pentaphyllum leaf extracts and their components, focusing on the inhibition of FLT3 and WT1 activity. METHODS: G. pentaphyllum extracts were prepared through maceration, yielding three crude fractional extracts. The cytotoxicity of the extracts was screened against various leukemia cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The most cytotoxic extract was further fractionated and purified via column chromatography. The anti-proliferative and apoptotic induction activities of the active extract and its fraction were evaluated through cell cycle and apoptosis analyses using flow cytometry. Changes in mitochondrial membrane potential (ΔΨm) were assessed by spectrofluorometry. To confirm anti-leukemia activity, the expression levels of FLT3, WT1 and apoptotic-related protein were analyzed using Western blotting. The major active compounds within the active fractions were identified and characterized using Electrospray Ionization Mass Spectrometry (ESI-MS) and Nuclear Magnetic Resonance (NMR) spectroscopy. RESULTS: The ethyl acetate fractional extract (F-EtOAc) demonstrated the highest cytotoxicity, particularly against FLT3-overexpressing EoL-1 (IC50 = 40.82 ± 0.8 µg/mL) and MV4-11 (IC50 = 35.54 ± 4.1 µg/mL) AML cell lines. Fraction F10 was identified as the most active fraction, significantly inhibited FLT3 and WT1 protein expression and induced G0/G1 cell cycle arrest in a dose-dependent manner. Additionally, F10 induced dose-dependent apoptosis through disruption of ΔΨm, p53 up-regulation and caspase-3 activation. Further purification of F10 identified dehydrovomifoliol as its major bioactive compound. CONCLUSION: These findings suggest that the ethyl acetate extract of G. pentaphyllum contains bioactive compounds with anti-leukemia potential, warranting further investigation to evaluate its efficacy against AML. CLINICAL TRIAL NUMBER: Not applicable.

With a number of biologically active members, 2‐aroylchromones are valuable synthetic targets. A direct route towards 2‐aroylchromones from 2‐(methylsulfonyl)chromones and aldehydes via NHC‐catalyzed C‐C bond formation was developed. Yields of the synthesized 2‐aroylchromones were up to 85%. Chromones with angioprotective or antibacterial properties were easily synthesized using the method developed. Additionally, the synthetic utility of the afforded chromones was demonstrated by using them to synthesize the anticancer compound wrightiadione and analogues of it.