Unlocking the Immunomodulatory Potential of Rosmarinic Acid Isolated from Punica granatum L. using Bioactivity-Guided Approach: In Silico, In Vitro, and In Vivo Approaches

Author:

Gautam Rupesh K.12,Tripathi Shailesh Mani3,Akash Shopnil4,Sharma Sanjay5,Sharma Komal6,Goyal Swapnil7,Behzad Sahar8,Gundamaraju Rohit910,Mishra Dinesh Kumar11,Zhang Yingbo1,Shen Bairong1,Sundriyal Sandeep3,Singla Rajeev K.112ORCID

Affiliation:

1. Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China

2. Indore Institute of Pharmacy, IIST Campus, Rau, Indore, 453331, (M.P.), India

3. Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan, 333031, India

4. Department of Pharmacy, Daffodil International University, Daffodil Smart City, Ashulia, Savar, Dhaka, 1207, Bangladesh

5. Department of Quality Assurance, Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMs NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra, 400056, India

6. Bhupal Nobles' College of Pharmacy, Bhopal Noble's University, Udaipur, 313001, India

7. Faculty of Pharmacy, Mandsaur University, Mandsaur, 458001, India

8. Evidence-based Phytotherapy and Complementary Medicine Research Center, Alborz University of Medical Sciences, Karaj, Iran

9. ER stress and mucosal immunology lab, School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia

10. School of Medicine, University of California San Francisco, San Francisco, California, United States of America

11. Department of Pharmacy, Guru Ghasidas Vishwavidyalaya (A Central University) Koni, Bilaspur (C.G.), 495009, India

12. School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India

Abstract

Background: Punica granatum L. is well-known for its multifaceted therapeutic potential, including anti-inflammatory and immunomodulatory activities. Aim: This study aimed to characterize an immunomodulatory compound isolated from Punica granatum L. using a bioactivity-guided approach. Methods: Chromatographic techniques were adopted for isolation and purification of secondary metabolites. In silico, in vitro, and in vivo methods were performed to characterize the therapeutic potential of the isolated compound. Results: Using preparative thin-layer chromatography, rosmarinic acid was isolated from F4 (column chromatography product obtained from a butanolic fraction of the extract). The impact of rosmarinic acid was assessed in rats using the neutrophil adhesion test, DTH response, and phagocytic index. In immunized rats, rosmarinic acid demonstrated significant immunomodulatory potential. Computational experiments, like molecular docking and molecular dynamics, were also conducted against two targeted receptors, Cereblon (PDB ID: 8AOQ) and human CD22 (PDB ID: 5VKM). Computational studies suggested that an increase in phagocytic index by rosmarinic acid could be attributed to inhibiting Cereblon and CD22. Pharmacokinetics and toxicity prediction also suggested the drug-likeness of rosmarinic acid. Conclusion: Rosmarinic acid is a potential candidate, but extensive research needs to be done to translate this molecule from bench to bedside.

Publisher

Bentham Science Publishers Ltd.

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