Investigating the molecular mechanisms of Ashwagandha phytocompounds in epilepsy through differential gene expression and pathway analysis

Srivarshini Govinda Srinivasan; Susha Dinesh; Sameer Sharma; Bhavana Sunkadakatte Venugopal; Martin Lucas A.; Dinesh Sosalagere Manjegowda

doi:10.51248/.v43i5.2870

Authors

Srivarshini Govinda Srinivasan https://orcid.org/0009-0006-2673-1858
Susha Dinesh https://orcid.org/0000-0001-6593-3803
Sameer Sharma https://orcid.org/0000-0002-3456-0263
Bhavana Sunkadakatte Venugopal https://orcid.org/0009-0001-0761-2574
Martin Lucas A. https://orcid.org/0000-0003-0082-0191
Dinesh Sosalagere Manjegowda

DOI:

https://doi.org/10.51248/.v43i5.2870

Keywords:

KCNQ2, SCN1A, SCN9A, epilepsy, ashwagandha root

Abstract

Introduction and Aim: Withania somnifera (Ashwagandha) is a traditional Indian herb used in Ayurveda and Unani medicine, particularly in anti-inflammatory, anti-cancer, anti-stress, antioxidant, immune-boosting, and rejuvenating effects. Epilepsy is a severe neuropsychological condition that occurs sporadically and has a long-term effect on the electrical signals that travel between brain cells. The disorder is characterized by recurrent seizures that are brought on by a sudden increase in brain electrical activity. This is the outcome of abnormal neuronal discharges or coordinated neuronal hyperexcitability. The study’s main objective is to find out the therapeutic phytocompound in treating Epileptic disorder.

Materials and Methods: This study investigated the potential use of phytochemicals from the Ashwagandha plant as epileptic seizure treatments that target key genes strongly associated with the disease. To forecast the binding affinity between the phytochemicals and the receptors, molecular docking simulations (PyRx) were used for the virtual screening.

Results: The preliminary screening of the twenty-two phytocompounds from Withania somnifera was based on their affinity for epilepsy. The results showed that withasomnine exhibited great binding affinity to the receptors, indicating their potential as targeted epileptic seizure therapeutics. The ligands revealed stronger binding with the epilepsy targets, and the binding score less than -7 kcal/mol was taken into consideration for further exploration. This research lays the groundwork for upcoming in-vitro and in-vivo studies to confirm the effectiveness of these phytochemicals as cancer therapies.

Conclusion: The results suggest that withasomnine derivatives from Withania somnifera could be a promising source of epilepsy therapies.

Author Biographies

Srivarshini Govinda Srinivasan

Department of Human Genetics, School of Basic and Applied Sciences, Dayananda Sagar University, Bangalore, 560078, Karnataka, India

Susha Dinesh

Department of Bioinformatics, BioNome, Bangalore, 560078, Karnataka, India

Sameer Sharma

Department of Bioinformatics, BioNome, Bangalore, 560078, Karnataka, India

Bhavana Sunkadakatte Venugopal

Department of Human Genetics, School of Basic and Applied Sciences, Dayananda Sagar University, Bangalore, 560078, Karnataka, India

Martin Lucas A.

Department of Anatomy, Dr. Chandramma Dayananda Sagar Institute of Medical Education & Research, Devarakaggalahalli, Harohalli, Kanakapura Road, Ramanagara Dt., 562 112, Karnataka, India

Dinesh Sosalagere Manjegowda

Department of Human Genetics, School of Basic and Applied Sciences, Dayananda Sagar University, Bangalore, 560078, Karnataka, India

References

Mayuri, B., Kumar, D.S., Kishore, P. A Review on epilepsy. Journal of Medical Science and Clinical Research. 2019; 7(3):1362-1369.

Raju, G.P., Dwajani, S., Rajendran, K., Adarsh, E. A study of rationale use of sodium valproate and levetiracetam as monotherapy in pediatric patients with epilepsy at tertiary care hospital. Biomedicine. 2022 Mar 5;42(1):160-164.

Mahmood, I.A., Muslim, A.T., Kaddoori, H.G. The utility of hematological indices in differentiation between general and focal onset epilepsy. Biomedicine. 2022 Mar 5;42(1):64-71.

Mishra, A., Batham, L., Verma, S., Mishra, S., Shrivastava, V. Management of epileptic seizures through an integrated approach including yagya therapy. Interdisciplinary Journal of Yagya Research. 2019;2(1):52-64.

Beghi, E. The epidemiology of epilepsy. Neuroepidemiology. 2020;54(2):185-191.

Bonilla-Jaime, H., Zeleke, H., Rojas, A., Espinosa-Garcia, C. Sleep disruption worsens seizures: neuroinflammation as a potential mechanistic link. International Journal of Molecular Sciences. 2021;22(22):12531.

Thijs, R.D., Surges, R., O'Brien, T.J., Sander, J.W. Epilepsy in adults. The Lancet. 2019;393(10172):689-701.

Yang, L., Wang, Y., Chen, X., Zhang, C., Chen, J., Cheng, H., et al., Risk factors for epilepsy: A national cross-sectional study from National Health and Nutrition Examination Survey 2013 to 2018. International Journal of General Medicine. 2021;14:4405-4411.

Safran, M., Rosen, N., Twik, M., BarShir, R., Stein, T.I., Dahary, D., et al., The GeneCards Suite. Pract. Guid. Life Sci. 2021;Databases 1, 27–56. https://doi.org/10.1007/978-981-16-5812-9_2.

Piñero, J., Ramírez-Anguita, J.M., Saüch-Pitarch, J., Ronzano, F., Centeno, E., Sanz, F., et al., The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic acids research. 2020;48(D1):D845-D855.

Hamosh, A., Amberger, J.S., Bocchini, C., Scott, A.F., Rasmussen, S.A. Online Mendelian inheritance in man (OMIM®): Victor McKusick's magnum opus. American Journal of Medical Genetics Part A. 2021;185(11):3259-3265.

Szklarczyk, D., Kirsch, R., Koutrouli, M., Nastou, K., Mehryary, F., Hachilif, R., et al., The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Research. 2023;51(D1):D638-D646.

Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., et al., PubChem 2023 update. Nucleic Acids Research. 2023; 51(D1):D1373-D1380.

Vivek-Ananth, R.P., Mohanraj, K., Sahoo, A.K., Samal, A. IMPPAT 2.0: an enhanced and expanded phytochemical atlas of Indian medicinal plants. ACS Omega. 2023;8(9):8827-8845.

UniProt Consortium. UniProt: The universal protein knowledgebase in 2023. Nucleic Acids Res. 2023;51(D1): D523-D531.

Burley, S.K., Bhikadiya, C., Bi, C., Bittrich, S., Chao, H., Chen, L., et al., RCSB Protein Data Bank (RCSB. org): Delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning. Nucleic Acids Research. 2023;51(D1):D488-D508.

Chang, Y., Hawkins, B.A., Du, J.J., Groundwater, P.W., Hibbs, D.E., Lai, F. A Guide to in silico drug design. Pharmaceutics. 2023;15(1):49.

Er-rajy, M., Imtara, H., Noman, O.M., Mothana, R.A., Abdullah, S., Zerougui, S., et al., QSAR, ADME-Tox, molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitor with memory enhancing properties. Heliyon. 2023;9(2): e13706.

Blazekovic, A., Gotovac, Jercic, K., Meglaj, S., Duranovic, V., Prpic, I., Lozic, B., et al., Genetics of pediatric epilepsy: Next-Generation Sequencing in Clinical Practice. Genes. 2022; 13(8):1466.

Umadevi, M., Rajeswari, R., Rahale, C. S., Selvavenkadesh, S., Pushpa, R., Kumar, K. S., et al., Traditional and medicinal uses of Withania somnifera. The Pharma Innovation.2012; 1(9):102-110.

Mandlik, D.S., Namdeo, A.G. Pharmacological evaluation of Ashwagandha highlighting its healthcare claims, safety, and toxicity aspects. Journal of Dietary Supplements. 2021;18(2):183-226.

Bhat, J.A., Akther, T., Najar, R.A., Rasool, F., Hamid, A. Withania somnifera (L.) Dunal (Ashwagandha); current understanding and prospect as a potential drug candidate. Frontiers in Pharmacology. 2022;13:1029123.

Pina, L.T., Guimarães, A.G., Sampaio, L.A., Guimarães, J.O., Rabelo, T.K., Savi, F.M., et al., Plant-based pharmacological alternatives in the seizure treatment: A patent review. Research, Society, and Development.2022;11(2): e40411225940.