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FLAVONOID-RICH EXTRACT OF VARTHEMIA IPHIONOIDES INCREASED LOW-DENSITY LIPOPROTEIN RECEPTOR AND DECREASED HYDROXYMETHYLGLUTARYL COA REDUCTASE EXPRESSION IN HEPG2 CELLS

MANAL M. ABBAS 1, MANAL A. ABBAS 1, WAEL MOHAMEDY AFIFI 2,3, YASSER IBRAHIM KANDIL 4,5*

1Department of Medical Lab. Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman, Jordan
2Pharmacognosy Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
3Pharmacognosy Department, Faculty of Pharmacy, Sinai University – Kantara Branch, Ismailia, Egypt
4Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
5Biochemistry Department, Faculty of Pharmacy, Sinai University – Kantara Branch, Ismailia, Egypt

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Varthemia iphionoides is a perennial herb that belongs to the Asteraceae family. In traditional medicine, it is used to alleviate abdominal pain, manage diabetes and aid in weight loss. This work aims to study the mechanism of its hypocholesterolaemia effect and identify the active constituents of its aerial parts. The hypocholesterolaemia effect of V. iphionoides extract was investigated in HepG2 cells by determining HMG-CoA reductase and low-density lipoprotein receptor (LDLR) gene expression using Q-PCR. The constituents of V. iphionoides extract were determined using a non-targeted profiling method using ultra- performance liquid chromatography coupled to a photodiode array. QTOF-MS was operated in positive ionisation mode. The half maximal inhibitory concentration (IC50) of V. iphionoides in HepG2 cells was 176.0 μg/mL after 24 h. V. iphionoides extract (88 μg/mL) significantly decreased HMG-CoA reductase gene expression, while 176 μg/mL of its aerial parts extract increased LDLR gene expression after 24 h incubation. QTOF-MS analysis resulted in the identification of 11 flavonoids, two phenolic compounds, nicotinamide and phenylalanine. In conclusion, this study reports for the first time that V. iphionoides downregulates HMG-CoA reductase and upregulates the LDLR gene. The latter mechanism functions in a manner akin to statins.