Withanolide from Ashwagandha plant, A, B, glycosides

Withanolides are a group of ergostane skeletal phytosteroids. Withanolides are structurally distinct from tropane / nortropane alkaloids (usually found in Solanaceae plants) and are produced only by a few genera within Solanaceae. Withania somnifera contains many structurally diverse withanolides in its leaves as well as roots. Withanolides are synthesized in leaves and transported to roots like the tropane alkaloids, a group of bioactive secondary metabolites in Solanaceae members known to be mostly synthesized in roots and transported to leaves for storage. See Ashwagandha supplement to purchase this product with withanolides.

Withanolide standardization
Many ashwagandha products are standardized to withanolides of 1 percent, 1.5 percent, 2 percent, 4 percent, and even higher.

Withanolide safety
Q. Can an ashwagandha herbal supplement that contains withanolides be taken daily for many months or years?
   A. Since the long term safety of withanolides is not fully understood, it would be a good idea to take a week off each month.

Types of withanolides
There are a number of withanolides including 27-hydroxy withanone, 17-hydroxy withaferin A, 17-hydroxy-27-deoxy withaferin A, withaferin A, withanolide D, 27-hydroxy withanolide B, withanolide A, withanone and 27-deoxywithaferin A.

Withanolides in Tubocapsicum anomalum
Several withanolides are found in the stems, roots, and leaves of Tubocapsicum anomalum.

Glioblastoma
Effect of the alcoholic extract of Ashwagandha leaves and its components on proliferation, migration, and differentiation of glioblastoma cells: Combinational approach for enhanced differentiation.
Cancer Sci. 2009 May 31. Shah N, Kataria H, Kaul SC, Ishii T, Kaur G, Wadhwa R. National Institute of Advanced Industrial Science and Technology, Graduate School of Life and Environmental Sciences, University if Tsukuba, Ibaraki, Japan.
Ashwagandha (Withania somnifera) is widely used in the Indian traditional system of medicine, Ayurveda. Although it is claimed to have a large variety of health-promoting effects, including therapeutic effects on stress and disease, the mechanisms of action have not yet been determined. In the present study, we aimed to investigate the growth inhibition and differentiation potential of the alcoholic extract of Ashwagandha leaves (i-Extract), its different constituents (Withaferin A, Withanone, Withanolide A) and their combinations on glioma (C6 and YKG1) cell lines. Withaferin A, Withanone, Withanolide A and i-Extract markedly inhibited the proliferation of glioma cells in a dose-dependent manner and changed their morphology toward the astrocytic type. Molecular analysis revealed that the i-Extract and some of its components caused enhanced expression of glial fibrillary acidic protein, change in the immunostaining pattern of mortalin from perinuclear to pancytoplasmic, delay in cell migration, and increased expression of neuronal cell adhesion molecules. The data suggest that the i-Extract and its components have the potential to induce senescence-like growth arrest and differentiation in glioma cells. These assays led us to formulate a unique combination formula of i-Extract components that caused enhanced differentiation of glial cells.

Withanolide kills leukemia cells in vitro
Withanolide induces apoptosis in HL-60 leukemia cells via mitochondria mediated cytochrome c release and caspase activation.
Chem Biol Interact. 2007 April. Senthil V, Ramadevi S, Venkatakrishnan V, Giridharan P, Lakshmi BS, Vishwakarma RA, Balakrishnan A.
Centre For Biotechnology, Anna University, Chennai 600025, Tamil Nadu, India.
The present study is on the growth inhibitory effect of Withania somnifera methanolic leaf extract and its active component, withanolide on HL-60 promyelocytic leukemia cells. Both the crude leaf extract and the active component activated the apoptotic cascade through the cytochrome c release from mitochondria. The activation of caspase 9, caspase 8 and caspase 3 revealed that caspase was a key mediator in the apoptotic pathway. DNA fragmentation analysis revealed typical ladders as early as 12h indicative of caspase 3 role in the apoptotic pathway. Flow cytometry data demonstrated an increase of sub-G1 peak upon treatment by 51% at 24h, suggesting the induction of apoptotic cell death in HL-60 cells.

Ashwagandha extract availability by herbal ingredient suppliers
Ashwagandha extract is available in a number of concentrations and extract potencies. These include 1 percent alkaloids, 1 percent withanolides, 1.5 percent withanolides, 2.5 percent withanolides, and 5 percent withanolides.

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