Nrf2-inducing and HMG-CoA reductase inhibitory activities of a polyphenol-rich fraction of Guazuma ulmifolia leaves
Sulistiyani1, Syamsul Falah2, Wulan Tri Wahyuni3, Dimas Andrianto2, Arthur Ario Lelono4, Waras Nurcholis1, Valeri Mossine5, Mark Hannink5
1 Tropical Biopharmaca Research Center of Excellence; Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University (Bogor Agricultural University), Bogor, Indonesia
2 Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University (Bogor Agricultural University), Bogor, Indonesia
3 Department of Chemistry, Faculty of Mathematics and Natural Sciences, IPB University (Bogor Agricultural University), Bogor, Indonesia
4 Chemistry Research Center, Indonesian Institute of Sciences, Serpong, Indonesia
5 Biochemistry Department, Christopher S. Bond Life Sciences Center, University of Missouri-Columbia, Columbia-MO, USA
Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University (Bogor Agricultural University), Bogor
Source of Support: None, Conflict of Interest: None
Objective: To fractionate and identify polyphenols from Guazuma ulmifolia Lam. leaves, and to explore their antioxidant, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitory, and Nrf2 modulatory activities.
Methods: The 1,1-diphenyl-2-picrylhydrazyl assay was used to evaluate the antioxidant activity of a polyphenolic fraction of the extract of Guazuma ulmifolia Lam. leaves. THP-1 gene reporter cell lines constructed with a transcriptional response element specific for Nrf2 and a minimal promoter for the firefly luciferase–green fluorescent protein transgene were used to determine the effect of the polyphenolic fraction on the Nrf2 signaling pathway. Furthermore, an assay of HMG-CoA reductase inhibitory activity was performed by using a commercial enzyme kit. Polyphenolic compounds were identified by liquid chromatography-tandem mass spectrometry.
Results: The polyphenolic fraction showed fairly strong antioxidant activity [IC50 = (14.90 ± 4.70) μg/mL] and inhibited HMG-CoA reductase activity by 69.10%, which was slightly lower than that by pravastatin (84.37%) and quercetin (84.25%). Additionally, the polyphenolic fraction activated the Nrf2 antioxidant signaling pathway at 500 μg/mL. Eleven subfractions resulting from the column chromatography separation of the polyphenolic fraction also showed relatively strong antioxidant activities (IC50: 17.46μ217.14 μg/mL). The subfraction (F6) stimulated the Nrf2 signaling pathway and had HMG-CoA reductase inhibitory activity (65.43%). Moreover, the subfraction contained two main flavonoids: quercetin and quercimeritrin.
Conclusions: The polyphenolic fraction of Guazuma ulmifolia could induce antioxidant genes via the Nrf2/antioxidant regulatory elements pathway, and is a promising candidate for an inhibitor of HMG-CoA reductase.