title: Phytochemicals and botanical extracts regulate NF-κB and Nrf2/ARE reporter activities in DI TNC1 astrocytes.
abstract: The increase in oxidative stress and inflammatory responses associated with neurodegenerative diseases has drawn considerable attention towards understanding the transcriptional signaling pathways involving NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and Nrf2 (Nuclear Factor Erythroid 2-like 2). Our recent studies with immortalized murine microglial cells (BV-2) demonstrated effects of botanical polyphenols to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) and enhance Nrf2-mediated antioxidant responses (Sun et al., 2015). In this study, an immortalized rat astrocyte (DI TNC1) cell line expressing a luciferase reporter driven by the NF-κB or the Nrf2/Antioxidant Response Element (ARE) promoter was used to assess regulation of these two pathways by phytochemicals such as quercetin, rutin, cyanidin, cyanidin-3-O-glucoside, as well as botanical extracts from Withania somnifera (Ashwagandha), Sutherlandia frutescens (Sutherlandia) and Euterpe oleracea (Açaí). Quercetin effectively inhibited LPS-induced NF-κB reporter activity and stimulated Nrf2/ARE reporter activity in DI TNC1 astrocytes. Cyanidin and the glycosides showed similar effects but only at much higher concentrations. All three botanical extracts effectively inhibited LPS-induced NF-κB reporter activity. These extracts were capable of enhancing ARE activity by themselves and further enhanced ARE activity in the presence of LPS. Quercetin and botanical extracts induced Nrf2 and HO-1 protein expression. Interestingly, Ashwagandha extract was more active in inducing Nrf2 and HO-1 expression in DI TNC1 astrocytes as compared to Sutherlandia and Açaí extracts. In summary, this study demonstrated NF-kB and Nrf2/ARE promoter activities in DI TNC1 astrocytes, and further showed differences in ability for specific botanical polyphenols and extracts to down-regulate LPS-induced NF-kB and up-regulate the NRF2/ARE activities in these cells.
authors.affiliation: Biochemistry Department, University of Missouri, Columbia, MO, USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Ajit
authors.affiliation: Biochemistry Department, University of Missouri, Columbia, MO, USA; Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
authors.forename: Agnes
authors.initials: A
authors.lastname: Simonyi
authors.affiliation: Biochemistry Department, University of Missouri, Columbia, MO, USA.
authors.forename: Runting
authors.initials: R
authors.lastname: Li
authors.affiliation: Biochemistry Department, University of Missouri, Columbia, MO, USA.
authors.forename: Zihong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Biochemistry Department, University of Missouri, Columbia, MO, USA; Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Hannink
authors.affiliation: Department of Animal Sciences, University of Missouri, Columbia, MO, USA; Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Fritsche
authors.affiliation: Biochemistry Department, University of Missouri, Columbia, MO, USA; Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
authors.forename: Valeri V
authors.initials: VV
authors.lastname: Mossine
authors.affiliation: U.S. FDA, Lenexa, KS, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Smith
authors.affiliation: U.S. FDA, Lenexa, KS, USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Dobbs
authors.affiliation: Department of Chemistry and Biochemistry, University of Missouri, St. Louis, MO, USA.
authors.forename: Rensheng
authors.initials: R
authors.lastname: Luo
authors.affiliation: Biochemistry Department, University of Missouri, Columbia, MO, USA; Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Folk
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA; Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
authors.forename: Zezong
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Biochemistry Department, University of Missouri, Columbia, MO, USA; Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
authors.forename: Dennis B
authors.initials: DB
authors.lastname: Lubahn
authors.affiliation: Biochemistry Department, University of Missouri, Columbia, MO, USA.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Weisman
authors.affiliation: Biochemistry Department, University of Missouri, Columbia, MO, USA; Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA. Electronic address: sung@missouri.edu.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Sun
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000187:drug effects / Q000502:physiology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D064209:Phytochemicals / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats
chemical_list: D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D064209:Phytochemicals; D010936:Plant Extracts
keywords: ARE reporter; Ashwagandha; Açaí; NF-κB reporter; Quercetin; Sutherlandia