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Experimental validation and network pharmacology evaluation to decipher the mechanism of action of Erythrina variegata L. bark against scopolamine-induced memory impairment in rats

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Abstract

This paper aimed to elucidate the effect of Erythrina variegata L. bark on scopolamine-induced memory impairment in rats and to decipher the molecular mechanism of phytoconstituents via the utilization of gene set enrichment analysis, network pharmacology coupled with in silico docking study. First, three models i.e. Morris Water Maze (MWM), Elevated Plus Maze (EPM), and Passive Avoidance Paradigm (PA) were utilized to elucidate the memory function. Second, the level of biomarkers i.e. acetylcholinesterase enzyme, reduced glutathione, and lipid peroxidation level were measured in brain tissues. Third, the key bioactive phytoconstituents targeting potential protein targets and pathways were identified through gene set enrichment analysis and network pharmacology. Lastly, the interaction between bioactive phytoconstituents with their respective targets was confirmed by molecular docking analysis. The MWM, EPM, and PA activity showed, scopolamine administration increased Escape Latency Time (ELT), Transfer Latency (TL), and Step Through Latency (STL) respectively on day 0th, 7th, 14th, and 21st, whereas treatment with E. variegata extract significantly reverse the ELT, TL and STL activity. The decreased level of Acetylcholinesterase (AChE) and MDA level in treated animals reflected the enhanced memory and was found to be comparable withclinically proven drug i.e. donepezil. Sixty compounds were identified in EV bark, among which twenty-two compounds are predicted to modulate potential targets involved in AD and considered potentially bioactive. Further, the docking study revealed, Alpinumisoflavone, Auriculatin, Osajin, and Scandenone to have the highest binding affinity with Tau protein, Whereas Donepezil and Glucoerysodine with acetylcholinesterase enzyme.

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Acknowledgement

The authors thank the Vital Laboratories Pvt. Ltd, Gujarat for providing Scopolamine HBr and Apotex pharmaceuticals, Bangalore for providing Donepezil as a gift sample. Thanks to the Principal KLE College of Pharmacy, Belagavi for providing necessary facilities to conduct the work.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, 590010, India

    Prakash Biradar, Vishal Patil, Pukar Khanal & Shamanand Mallapur

  2. Department of Pharmacognosy, Sharadaha Vilas College of Pharmacy, Mysore, Karnataka, India

    Hanumanthachari Joshi

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  1. Prakash Biradar
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  2. Vishal Patil
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  3. Hanumanthachari Joshi
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  4. Pukar Khanal
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  5. Shamanand Mallapur
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Contributions

Prakash Biradar designed the study, conducted the experiments and written and drafted the manuscript Vishal Patil performed insilico studies and data analysis. Dr. Hanumanthachare Joshi supervised the experiments. Pukar Khanal and Shamanand Mallapur assisted in data analysis and reviewed the manuscript.

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Correspondence to Prakash Biradar.

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Ethical statement

The study protocol was reviewed and approved by the Institutional Animal Ethical Committee, KLE College of Pharmacy, Belagavi, and Resolution No. KLECOP/CPCSEAReg. No. 221/Po/Re/S/2000/CPCSEA, Res. 25–13/10/2018. The animal experiments were carried out in accordance with the CPCSEA guidelines.

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Biradar, P., Patil, V., Joshi, H. et al. Experimental validation and network pharmacology evaluation to decipher the mechanism of action of Erythrina variegata L. bark against scopolamine-induced memory impairment in rats. ADV TRADIT MED (ADTM) 22, 193–206 (2022). https://doi.org/10.1007/s13596-020-00524-9

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