Isosakuranetin

Isosakuranetin is a flavanone that has been found in Citrus species and has diverse biological activities.^{1,2,3,4,5,6,7} It inhibits calcium uptake induced by pregnenolone sulfate in HEK293 cells expressing mouse transient receptor potential melastatin 3 (TRPM3; IC₅₀ = 50 nM).¹ Isosakuranetin is selective for TRPM3 over TRPM1, TRPM8, and TRP vanilloid-related 1 (TRPV1) when used at a concentration of 10 μM. In vivo, isosakuranetin (2 mg/kg) increases latency to first pain-related response in mice in a hot plate test and reduces the number and duration of PregS-induced nocifensive responses, such as paw licking, shaking, or lifting, in mice. It also reduces systolic blood pressure in spontaneously hypertensive rats when administered at a dose of 10 mg/kg.² Isosakuranetin (20 ?M) inhibits UV-B-induced matrix metalloproteinase-1 (MMP-1) expression by 90% in HaCaT human keratinocyte cells, as well as phosphorylation of ERK1/2 when used at a concentration of 50 ?M.³ It blocks hydrogen peroxide-induced increases in reactive oxygen species (ROS), intracellular calcium concentration, caspase-3 activity, and JNK phosphorylation, as well as decreases in catalase activity, in PC12 cells when used at a concentration of 0.8 ?M.⁴ Isosakuranetin also has antibacterial and trypanocidal activity against M. tuberculosis, C. neoformans, and T. cruzi.^5,6,7

1.Straub, I., Krügel, U., Mohr, F., et al.Flavanones that selectively inhibit TRPM3 attenuate thermal nociception in vivoMol. Pharmacol.84(5)736-750(2013) 2.Maruyama, H., Sumitou, Y., Sakamoto, T., et al.Antihypertensive effects of flavonoids isolated from brazilian green propolis in spontaneously hypertensive ratsBiol. Pharm. Bull.32(7)1244-1250(2009) 3.Jung, H., Lee, E.H., Lee, T.H., et al.The methoxyflavonoid isosakuranetin suppresses UV-B-induced matrix metalloproteinase-1 expression and collagen degradation relevant for skin photoagingInt. J. Mol. Sci.17(9)E1449(2016) 4.Hwang, S.-L., and Yen, G.-C.Modulation of Akt, JNK, and p38 activation is involved in citrus flavonoid-mediated cytoprotection of PC12 cells challenged by hydrogen peroxideJ. Agric. Food Chem.57(6)2576-2582(2009) 5.Suksamrarn, A., Chotipong, A., Suavansri, T., et al.Antimycobacterial activity and cytotoxicity of flavonoids from the flowers of Chromolaena odorataArch. Pharm. Res.27(5)507-511(2004) 6.da Silva Filho, A.A., de Sousa, J.P., Soares, S., et al.Antimicrobial activity of the extract and isolated compounds from Baccharis dracunculifolia D. C. (Asteraceae)Z. Naturforsch. C.63(1-2)40-46(2008) 7.da Silva Filho, A.A., Pires Bueno, P.C., Gregório, L.E., et al.In-vitro trypanocidal activity evaluation of crude extract and isolated compounds from Baccharis dracunculifolia D.C. (Asteraceae)J. Pharm. Pharmacol.56(9)1195-1199(2004)