Background
Yangonin is a natural kavalactone from the kava plant, P. methysticum. It enhances the binding of bicuculline at the γ-amino butyric acid (GABA) receptor GABAA at 1.0 ?M.1 Yangonin also binds the central cannabinoid (CB1) receptor with a Ki value of 0.72 ?M, but whether it serves as an agonist or antagonist at this receptor remains to be determined.2 Yangonin blocks the activation of NF-κB by TNF-α.3 It also inhibits anchorage-dependent and independent growth of bladder cancer cell lines through induction of autophagic cell death (IC50s = 15-59 mg/mL).4
1.Boonen, G., and H?berlein, H.Influence of genuine kavapyrone enantiomers on the GABAA binding sitePlanta Med.64(6)504-506(1998)
2.Ligresti, A., Villano, R., Allará, M., et al.Kavalactones and the endocannabinoid system: The plant-derived yangonin is a novel CB1 receptor ligandPharmacol. Res.66(2)163-169(2012)
3.Ma, J., Liang, H., Jin, H.R., et al.Yangonin blocks tumor necrosis factor-α-induced nuclear factor-κB-dependent transcription by inhibiting the transactivation potential of the RelA/p65 subunitJ. Pharmacol. Sci.118(4)447-454(2012)
4.Zhongbo, L., U-Syn, H., Ke, Y., et al.Kavalactone yangonin induces autophagy and sensitizes bladder cancer cells to flavokawain A and docetaxel via inhibition of the mTOR pathwayJ. Biomed. Res.(2017)
Protocol
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Cell experiment:
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HeLa cells are seeded at 1×105 cells/mL in 96-well plates containing 100 μL of DMEM medium with 10% FBS and incubated overnight. Yangonin is dissolved in DMSO and DMSO is added to all plates to compensate the same volume of DMSO. After 24 h, the cells are pretreated with different concentrations of Yangonin (0.1-3 μM) for 1 h, followed by stimulation with or without TNF-α for 24 h. Subsequently, cells are cultured with MTT solution (5 mg/mL) for 3 h. The viable cells convert MTT to formazan, which generates a blue-purple color after dissolving in 150 μL of DMSO. The absorbance at 570 nm is measured by an ELISA plate reader[2].
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参考文献:
[1]. Ligresti A, et al. Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB1 receptor ligand. Pharmacol Res. 2012 Aug;66(2):163-9.
[2]. Ma J, et al. Yangonin blocks tumor necrosis factor-α-induced nuclear factor-κB-dependent transcription by inhibiting the transactivation potential of the RelA/p65 subunit. J Pharmacol Sci. 2012;118(4):447-54.
[3]. Wruck CJ, et al. Kavalactones protect neural cells against amyloid beta peptide-induced neurotoxicity via extracellular signal-regulated kinase 1/2-dependent nuclear factor erythroid 2-related factor 2 activation. Mol Pharmacol. 2008 Jun;73(6):1785-95.
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