Effect of Indian Ayurvedic Medicine Ashwagandha on Measurement of Serum Digoxin and 11 Commonly Monitored Drugs Using Immunoassays: Study of Protein Binding and Interaction with Digibind (Report‪)‬

Ashwagandha (Withania somnifera), also known as winter cherry, belongs to the pepper family and is found in India and Africa, as well as in North America. Ashwagandha roots have been used in Indian Ayurvedic medicine for more than 3000 years as an aphrodisiac, liver tonic, anti-inflammatory agent, and astringent. Traditional use of Ashwagandha among tribal peoples in Africa includes treating fever and inflammatory conditions. Preliminary research indicates that Ashwagandha may be effective for treating anxiety, cognitive and neurologic disorders, inflammation, and Parkinson disease. (1) Recently, several preparations of St John's wort were found to contain extract of Ashwagandha, as revealed by surveying product from several herbal stores in the Houston area. Ashwagandha extract is also used traditionally in Ayurvedic medicine for stimulation of the heart. However, pharmacologic and toxicologic effects of Ashwagandha on humans have not been established by rigorous scientific research. The major biochemical constituents of Ashwagandha are steroidal alkaloids and steroidal lactones in a class of compounds termed withanolides. Withaferin A (also a withanolide), a major constituent of Ashwagandha, has structural similarity with digoxin (Figure). Other novel withanolides have been isolated and characterized from Ashwagandha. 2-4 Withanolides also have some structural similarity with ginsenosides, the active component of Asian ginseng (Panax ginseng). We reported earlier that Asian ginseng interferes with the fluorescence polarization immunoassay (FPIA) and the microparticle enzyme immunoassay (MEIA) of digoxin but has no effect on the Beckman, Roche, or the chemiluminescent assay (Bayer, Tarrytown, NY). (5,6) Therefore, it was theorized that Ashwagandha may affect FPIA and MEIA assessment of digoxin. The possibility also exists that constituents of Ashwagandha may interfere with immunoassays of other therapeutic drugs. Moreover, herbal products are not prepared following rigorous pharmaceutical standard, and components of a herbal product may vary significantly between different manufacturers. Here we report findings of 3 different Ashwagandha products from 2 different manufacturers on the FPIA, MEIA, and Beckman assay of digoxin. We also report that Ashwagandha does not interfere with immunoassays of 11 other drugs monitored routinely in clinical laboratories. The potential neutralization of digoxin-like immunoreactive components of Ashwagandha by the Fab fragment of antidigoxin antibody (Digibind) was also examined.