Preprint / Version 1

Natural Withanolides in the Treatment of Chronic Diseases

Authors

  • Peter White Department of Surgery, University of Michigan Hospital and Health Systems, 2920K Taubman Center, SPC 5331, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5331 USA
  • Chitra Subramanian Department of Surgery, University of Michigan Hospital and Health Systems, 2920K Taubman Center, SPC 5331, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5331 USA
  • Hashim Motiwala Department of Surgery, University of Michigan Hospital and Health Systems, 2920K Taubman Center, SPC 5331, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5331 USA
  • Mark Cohen Department of Surgery, University of Michigan Hospital and Health Systems, 2920K Taubman Center, SPC 5331, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5331 USA

Keywords:

Autoimmune, Cancer, Inflammation, Neurodegenerative, NF-κB, Withaferin A, Withanolide

Abstract

Withanolides, and in particular extracts from Withania somnifera, have been used for over 3,000 years in traditional Ayurvedic and Unani Indian medical systems as well as within several other Asian countries. Traditionally, the extracts were ascribed a wide range of pharmacologic properties with corresponding medical uses, including adaptogenic, diuretic, anti-inflammatory, sedative/anxiolytic, cytotoxic, antitussive, and immunomodulatory. Since the discovery of the archetype withaferin A in 1965, approximately 900 of these naturally occurring, polyoxygenated steroidal lactones with 28-carbon ergostane skeletons have been discovered across 24 diverse structural types. Subsequently, extensive pharmacologic research has identified multiple mechanisms of action across key inflammatory pathways. In this chapter we identify and describe the major withanolides with anti-inflammatory properties, illustrate their role within essential and supportive inflammatory pathways (including NF-κB, JAK/STAT, AP-1, PPARγ, Hsp90 Nrf2, and HIF-1), and then discuss the clinical application of these withanolides in inflammation-mediated chronic diseases (including arthritis, autoimmune, cancer, neurodegenerative, and neurobehavioral). These naturally derived compounds exhibit remarkable biologic activity across these complex disease processes, while showing minimal adverse effects. As novel compounds and analogs continue to be discovered, characterized, and clinically evaluated, the interest in withanolides as a novel therapeutic only continues to grow. Keywords: Autoimmune, Cancer, Inflammation, Neurodegenerative, NF-κB, Withaferin A, Withanolide

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