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

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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.

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Acknowledgments

This work was partially supported by grant P50AT006273 from the National Center for Complementary and Alternative Medicine (NCCAM), the Office of Dietary Supplements (ODS), and the National Cancer Institute (NCI). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM, ODS, NCI, or the NIH.

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Authors and Affiliations

  1. Biochemistry Department, University of Missouri, 117 Schweitzer Hall, Columbia, MO, 65211, USA

    Grace Y. Sun, Runting Li, Mark Hannink, Dennis B. Lubahn & Agnes Simonyi

  2. Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, USA

    Grace Y. Sun, Jiankun Cui & Zezong Gu

  3. Department of Animal Sciences, University of Missouri, Columbia, MO, USA

    Kevin L. Fritsche & Dennis B. Lubahn

  4. MU Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, USA

    Grace Y. Sun, Runting Li, Jiankun Cui, Mark Hannink, Zezong Gu, Kevin L. Fritsche, Dennis B. Lubahn & Agnes Simonyi

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  1. Grace Y. Sun
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Sun, G.Y., Li, R., Cui, J. et al. Withania somnifera and Its Withanolides Attenuate Oxidative and Inflammatory Responses and Up-Regulate Antioxidant Responses in BV-2 Microglial Cells. Neuromol Med 18, 241–252 (2016). https://doi.org/10.1007/s12017-016-8411-0

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