In vitro effect of Withania somnifera, AYUSH-64, and remdesivir on the activity of CYP-450 enzymes: Implications for possible herb−drug interactions in the management of COVID-19
Authors
Siva Kasarla
Translational Health Science and Technology Institute (THSTI), Faridabad, India
Swapnil Borse
AYUSH - Center of Excellence (AYUSH-CoE), Center for Complementary and Integrative Health [CCIH], Interdisciplinary School of Health Sciences (ISHS), Savitribai Phule Pune University Pune (SPPU), Pune, India
Yashwant Kumar
Translational Health Science and Technology Institute (THSTI), Faridabad, India
Neha Sharma
Translational Health Science and Technology Institute (THSTI), Faridabad, India
Madhu Dikshit
Translational Health Science and Technology Institute (THSTI), Faridabad, India
Ayurvedic medicines Withania somnifera Dunal (ashwagandha) and AYUSH-64 have been used for the prevention and management of COVID-19 in India. The present study explores the effect of Ashwagandha and AYUSH-64 on important human CYP enzymes (CYP3A4, CYP2C8, and CYP2D6) to assess their interaction with remdesivir, a drug used for COVID-19 management during the second wave. The study also implies possible herb−drug interactions as ashwagandha and AYUSH-64 are being used for managing various pathological conditions. Aqueous extracts of ashwagandha and AYUSH-64 were characterized using LC-MS/MS. A total of 11 and 24 phytoconstituents were identified putatively from ashwagandha and AYUSH-64 extracts, respectively. In addition, in silico studies revealed good ADME properties of most of the phytoconstituents of these herbal drugs and suggested that some of these might possess CYP-450 inhibitory activity. In vitro CYP-450 studies with human liver microsomes showed moderate inhibition of CYP3A4, 2C8, and 2D6 by remdesivir, while ashwagandha had no inhibitory effect alone or in combination with remdesivir. AYUSH-64 also exhibited a similar trend; however, a moderate inhibitory effect on CYP2C8 was noticed. Thus, ashwagandha seems to be safe to co-administer with the substrates of CYP3A4, CYP2C8, and CYP2D6. However, caution is warranted in prescribing AYUSH-64 along with CYP2C8 substrate drugs. Furthermore, preclinical and clinical PK studies would be helpful for their effective and safer use in the management of various ailments along with other drugs.
Keywords: Withania somnifera, Ayurveda, remdesivir, integrative medicine, Rasayana, LC-MS/MS, AYUSH-64, herb−drug interaction
Author Biographies
Siva Kasarla, Translational Health Science and Technology Institute (THSTI), Faridabad, India
Spatial Metabolomics Group, Leibniz-Institut für Analytische Wissenschaften-ISAS-e V, Dortmund, Germany
Neha Sharma, Translational Health Science and Technology Institute (THSTI), Faridabad, India
Department of Pharmaceutical Analysis, Delhi Pharmaceutical Science and Research University, Pushp Vihar, New Delhi, India
Madhu Dikshit, Translational Health Science and Technology Institute (THSTI), Faridabad, India
CSIR- Central Drug Research Institute, Lucknow, Uttar Pradesh, India
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