28-day repeated dose toxicological evaluation of Coronil in Sprague Dawley rats: Behavioral, hematological, biochemical and histopathological assessments under GLP compliance

Abstract

Ayurvedic medicines are widely employed globally for prophylaxis and treatment of a variety of diseases. Coronil is a tri-herbal medicine, constituted with the traditional herbs, Tinospora cordifolia, Withania somnifera and Ocimum sanctum, with known immunomodulatory activities. Based on its proven in-vitro activity and in-vivo efficacy, Coronil has been approved as a ‘Supporting Measure for COVID-19’ by the Ministry of AYUSH, Government of India. The current study was aimed to assess the non-clinical safety of Coronil in a 28-day repeated dose toxicity study along with a 14-day recovery period in Sprague Dawley rats. This toxicity study was conducted in accordance with OECD test guideline 407, under GLP-compliance. Specific-Pathogen-Free animals of either sex, housed in Individually-Ventilated-Cages were particularly used in the study. The tested Coronil dose levels were 0, 100, 300 and 1000 mg/kg/day, orally administered to 5 males and 5 female rats per test group. In the current study, no mortality was observed in any group and in addition, Coronil did not elicit any finding of toxicological relevance with respect to clinical signs, ocular effects, hematology, urinalysis and clinical chemistry parameters, as well as macro- or microscopical changes in any organs, when compared to the control group. Accordingly, the No-Observed-Adverse-Effect-Level (NOAEL) of Coronil was ascertained to be 1000 mg/kg/day, subsequent to its 28-day oral administration to male and female rats. The acceptable safety profile of Coronil paves the way further toxicity assessments in rodents for a longer duration as well as in higher animals, and towards its clinical investigation.

Keywords:

• 28-day repeated dose toxicity
• Coronil
• OECD 407
• GLP
• Ayurveda

Acknowledgements

We thank Dr. Pralhad Wangikar, Dr. Sachin Shinde, Dr Sneha Thorat, and the scientific staff at PRADO, Pune, India for conducting this GLP Toxicity study in a blinded fashion; Dr. Jyotish Srivastava and Ms. Meenu Tomer for analytical chemistry supports. We extend our gratitude to Mr. Tarun Rajput, Mr. Gagan Kumar and Mr. Lalit Mohan for their swift administrative supports.

Author contributions

A.B. provided broad direction for the study, identified the test formulations, generated resources and gave final approval for the manuscript; S.S. monitored the in-vivo study, performed data curing, and wrote the manuscript; A.V. monitored, supervised overall studies, generated resources, critically reviewed and finally approved the manuscript. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

The test article, Coronil is an approved ayurvedic medicine and was manufactured by Divya Pharmacy, Haridwar, Uttarakhand, India. Besides, providing the test article, Divya Pharmacy was not involved in any aspect of this study. Acharya Balkrishna is a trustee in Divya Yog Mandir Trust, Haridwar, India that governs Divya Pharmacy, Haridwar. In addition, Acharya Balkrishna is one of the founding promoter and holds an honorary managerial position in Patanjali Ayurved Ltd, Haridwar, India. Divya Pharmacy and Patanjali Ayurved Ltd commercially manufacture and sell several ayurvedic products. All other authors, Sandeep Sinha and Anurag Varshney, have been employed at Patanjali Research Institute which is governed by Patanjali Research Foundation Trust (PRFT), Haridwar, Uttarakhand, India. PRFT is an independent not-for-profit organization. In addition, Anurag Varshney is an Adjunct Professor in Department of Allied and Applied Sciences, University of Patanjali, Haridwar, India; and in Special Center for Systems Medicine, Jawaharlal Nehru University, New Delhi, India. All other authors declare no conflict of interest.

Additional information

Funding

This presented work has been conducted using internal research funds from Patanjali Research Foundation Trust, Haridwar, India.