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

Rupesh K Gautam; Shailesh Mani Tripathi; Shopnil Akash; Sanjay Sharma; Komal Sharma; Swapnil Goyal; Sahar Behzad; Rohit Gundamaraju; Dinesh Kumar Mishra; Yingbo Zhang; Bairong Shen; Sandeep Sundriyal; Rajeev K Singla

doi:10.2174/0109298673291064240227094654

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

Curr Med Chem. 2024 Mar 5. doi: 10.2174/0109298673291064240227094654. Online ahead of print.

Authors

Rupesh K Gautam^{1

2}, Shailesh Mani Tripathi³, Shopnil Akash⁴, Sanjay Sharma⁵, Komal Sharma⁶, Swapnil Goyal⁷, Sahar Behzad⁸, Rohit Gundamaraju^{9

10}, Dinesh Kumar Mishra¹¹, Yingbo Zhang¹, Bairong Shen¹, Sandeep Sundriyal¹², Rajeev K Singla^{1

13}

Affiliations

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 Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMs NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra, India-400056.
⁶ Bhupal Nobles' College of Pharmacy, 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 Birla Institute of Technology and Science, Pilani Department of Pharmacy Pil?ni India.
¹³ School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab-144411, India.

PMID: 38445701
DOI: 10.2174/0109298673291064240227094654

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.

Keywords: CD22; Cereblon; Punica granatum L.; immune response.; immunomodulatory activity; rosmarinic acid.