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Neuromolecular Med. 2016 Sep;18(3):241-52. doi: 10.1007/s12017-016-8411-0. Epub 2016 May 21.

Withania somnifera and Its Withanolides Attenuate Oxidative and Inflammatory Responses and Up-Regulate Antioxidant Responses in BV-2 Microglial Cells.

Sun GY1,2,3, Li R4,5, Cui J6,5, Hannink M4,5, Gu Z6,5, Fritsche KL7,5, Lubahn DB4,7,5, Simonyi A4,5.

Author information

1
Biochemistry Department, University of Missouri, 117 Schweitzer Hall, Columbia, MO, 65211, USA. sung@missouri.edu.
2
Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, USA. sung@missouri.edu.
3
MU Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA. sung@missouri.edu.
4
Biochemistry Department, University of Missouri, 117 Schweitzer Hall, Columbia, MO, 65211, USA.
5
MU Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA.
6
Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, USA.
7
Department of Animal Sciences, University of Missouri, Columbia, MO, USA.

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.

KEYWORDS:

Ashwagandha; HO-1; LPS; Microglia; NO; Nrf2; Withaferin A; Withanolide A

PMID:
27209361
DOI:
10.1007/s12017-016-8411-0
[Indexed for MEDLINE]

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