title: Withania somnifera and Its Withanolides Attenuate Oxidative and Inflammatory Responses and Up-Regulate Antioxidant Responses in BV-2 Microglial Cells.
abstract: Withania somnifera (L.) Dunal, commonly known as Ashwagandha, has been used in Ayurvedic medicine for promoting health and quality of life. Recent clinical trials together with experimental studies indicated significant neuroprotective effects of Ashwagandha and its constituents. This study is aimed to investigate anti-inflammatory and anti-oxidative properties of this botanical and its two withanolide constituents, namely, Withaferin A and Withanolide A, using the murine immortalized BV-2 microglial cells. Ashwagandha extracts not only effectively inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and reactive oxygen species (ROS) production in BV-2 cells, but also stimulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, leading to induction of heme oxygenase-1 (HO-1), both in the presence and absence of LPS. Although the withanolides were also capable of inhibiting LPS-induced NO production and stimulating Nrf2/HO-1 pathway, Withaferin A was tenfold more effective than Withanolide A. In serum-free culture, LPS can also induce production of long thin processes (filopodia) between 4 and 8 h in BV-2 cells. This morphological change was significantly suppressed by Ashwagandha and both withanolides at concentrations for suppressing LPS-induced NO production. Taken together, these results suggest an immunomodulatory role for Ashwagandha and its withanolides, and their ability to suppress oxidative and inflammatory responses in microglial cells by simultaneously down-regulating the NF-kB and upregulating the Nrf2 pathways.
authors.affiliation: Biochemistry Department, University of Missouri, 117 Schweitzer Hall, Columbia, MO, 65211, USA. sung@missouri.edu.|Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, USA. sung@missouri.edu.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA. sung@missouri.edu.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Sun
authors.affiliation: Biochemistry Department, University of Missouri, 117 Schweitzer Hall, Columbia, MO, 65211, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
authors.forename: Runting
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
authors.forename: Jiankun
authors.initials: J
authors.lastname: Cui
authors.affiliation: Biochemistry Department, University of Missouri, 117 Schweitzer Hall, Columbia, MO, 65211, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Hannink
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
authors.forename: Zezong
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Animal Sciences, University of Missouri, Columbia, MO, USA.|MU 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, 117 Schweitzer Hall, Columbia, MO, 65211, USA.|Department of Animal Sciences, University of Missouri, Columbia, MO, USA.|MU 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, 117 Schweitzer Hall, Columbia, MO, 65211, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
authors.forename: Agnes
authors.initials: A
authors.lastname: Simonyi
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D007155:Immunologic Factors / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D032341:Withania / Q000737:chemistry*; D054358:Withanolides / Q000494:pharmacology*
chemical_list: D007155:Immunologic Factors; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D054358:Withanolides
keywords: Ashwagandha; HO-1; LPS; Microglia; NO; Nrf2; Withaferin A; Withanolide A