Due to transition in the journal platform, the previously submitted articles, which are under process can be re-submitted here for quick process, kindly co-operate

Biomedicine

Volume: 43 Issue: 1

  • Open Access
  • Original Article

Cytoprotective and anti-inflammatory effect of ethanolic extract of Withania somnifera root in combination with doxycycline in rotenone induced cytotoxicity in neuroblastoma cell lines

Vishala Epuri1, Lavanya Prathap2, Venkateshwar Reddy1, B. Rajesh3, B. Ramesh4

1Department of Anatomy, SVS Medical College, Mahaboobnagar, Telangana, India
2Department of Anatomy, Saveetha Dental College and Hospital, SIMATS, Chennai, India
3Department of Anatomy, 4Department of Biochemistry, Arundathi Institute of Medical Sciences,
Dundigal (V), Gandimaisamma (M), Medchal-Malkajgiri Dist., HMDA Hyderabad, 500043, Telangana, India

Corresponding author: B. Ramesh. Email: [email protected]

Year: 2023, Page: 469-476, Doi: https://doi.org/10.51248/.v43i01.2232

Abstract

Introduction and Aim: Parkinson's disease (PD) is a neurodegenerative disorder that destroys dopaminergic neurons in the nigrostriatal area of the midbrain this results in a movement difficulty characterised by tremors, bradykinesia, and postural instability The present in vitro study is designed to assess the beneficial (cytoprotectant and anti-inflammatory) and cyto-toxicological effects of ethanolic Withania somnifera (Ashwagandha) root extract (EWSR) in presence of Rotenone (ROT) and other known neuroprotectants (Doxycycline and Ellagic acid).
Materials and Methods: The nine groups used in the in vitro studies were normal control, positive control (Rotenone or Rot), W. somnifera root extract (EWSR), Doxycycline (Doxy), Ellagic acid (EA), ROT with EWSR, ROT with doxy, ROT with EA, ROT with EWSR-doxy, and ROT with EWSR-doxy-EA. The EWSR, doxy and EA treatment was started on the 24th hour following the rotenone administration and continued for the next 36 hours. After the 36th hour of protective therapy, quantification of pro-inflammatory cytokines (ELISA), cell viability or analyses of neuronal cell loss, cell cycle analysis and molecular analysis (RTPCR) was performed as a part of assessment.
Results: Observations from the present in vitro studies clearly demonstrate the cytoprotective and anti-inflammatory properties of EWSR, and these beneficial or protective effects got enhanced when treated in combination with Doxy and EA indicating synergistic effect in the cells that were priorly treated with ROT, and later treated with EWSR, Doxy, and EA individually and in combination.
Conclusion: The findings imply that EWSR reduces the in vitro effects of ROT by acting as an anti-inflammatory and cytoprotective agent

Keywords: Rotenone (ROT); Withania somnifera root extract (EWSR); Doxycycline; Anti-inflammation; Parkinson’s disease.

References

1. Kouli, A., Torsney, K.M., Kuan, W.L. Parkinson’s disease: Etiology, neuropathology, and pathogenesis. In: Stoker TB, Greenland JC, editors. Parkinson’s Disease: Pathogenesis and Clinical Aspects (Internet). Brisbane (AU): Codon Publications; 2018. Chapter1. doi: 10.15586/ codonpublicationsparkinsonsdisease.2018.ch1

2. Salari, S., Bagheri, M. In vivo, in vitro and pharmacologic models of Parkinson's disease. Physiol Res. 2019; 68(1): 17-24.

3. Moradi, V.S., Nasrolahi, A., Ghaderi, S., Belali, R., Rashno, M., Farzaneh, M., et al., Mitochondrial dysfunction and Parkinson's disease: Pathogenesis and therapeutic strategies. Neurochem Res. 2023. doi: 10.1007/s11064-023-03904-0.

4. Lee, Y., Lee, S., Chang, S.C., Lee, J. Significant roles of neuroinflammation in Parkinson's disease: therapeutic targets for PD prevention. Arch Pharm Res. 2019; 42(5): 416-425.

5. Ibarra-Gutiérrez, M.T., Serrano-García, N.,Orozco-Ibarra, M. Rotenone-induced model of Parkinson’s Disease: Beyond mitochondrial complex I inhibition. Mol Neurobiol 2023; 60: 1929-1948.

6. Radad, K., Al-Shraim, M., Al-Emam, A., Wang, F., Kranner, B., Rausch, W.D., et al., Rotenone: from modelling to implication in Parkinson's disease. Folia Neuropathol. 2019;57(4):317-326.

7. Raza, C., Anjum, R., Shakeel, N.U.A. Parkinson's disease: Mechanisms, translational models and management strategies. Life Sci. 2019 June 1;226:77-90.

8. Betarbet, R., Sherer, T.B., MacKenzie, G., Garcia-Osuna, M., Panov, A.V., Greenamyre, J.T. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 2000; 3: 1301-1306.

9. Zhang, M., He, Q., Chen, G., Li, PA. Suppression of NLRP3 Inflammasome, pyroptosis, and cell death by NIM811 in rotenone-exposed cells as an in vitro model of Parkinson's disease. Neurodegener Dis. 2020; 20(2-3): 73-83.

10. Marogianni, C., Sokratous, M., Dardiotis, E., Hadjigeorgiou, G.M., Bogdanos, D., Xiromerisiou, G. Neurodegeneration

and inflammation-An interesting interplay in Parkinson's disease. Int J Mol Sci. 2020;21(22):8421.

11. Bhat, J., Damle, A., Vaishnav, P.P., Albers, R., Joshi, M., Banerjee, G.In vivo enhancement of natural killer cell activity through tea fortified with ayurvedic herbs. Phytother Res. 2010; 24:129-135.

12. Dutta, R., Khalil, R., Green, R., Mohapatra, S.S., Mohapatra, S. Withania somnifera (Ashwagandha) and Withaferin A: Potential in Integrative Oncology. Int J Mol Sci. 2019 Oct 25;20(21):5310.

13. Bhatnagar, M., Goel, I., Roy, T., Shukla, S.D., Khurana, S. Complete Comparison Display (CCD) evaluation of ethanol extracts of Centella asiatica and Withania somnifera shows that they can non-synergistically ameliorate biochemical and behavioural damages in MPTP induced Parkinson's model of mice. PLoS One. 2017; 12(5): e0177254.

14. Limanaqi, F., Biagioni, F., Busceti, C.L., Ryskalin, L., Polzella, M., Frati, A., et al., Phytochemicals bridging autophagy induction and alpha-synuclein degradation in parkinsonism. International Journal of Molecular Sciences. 2019; 20(13):3274.

15. Sikandan, A., Shinomiya, T., Nagahara, Y. Ashwagandha root extract exerts anti-inflammatory effects in HaCaT cells by inhibiting the MAPK/NF-κB pathways and by regulating cytokines. Int J Mol Med. 2018;42: 425-434.

16. Sangita, C., Chatterjee, P., Dey, P., Bhattacharya, S. Evaluation of Anti-inflammatory Effect of Ashwagandha: A preliminary study in vitro. Pharmacognosy Journal. 2012; 4(29): 47-49.

17. Gupta, M., Kaur, G. Withania somnifera as a potential anxiolytic and anti-inflammatory candidate against systemic lipopolysaccharide-induced neuroinflammation. Neuromol Med. 2018; 20 (3): 343-362.

18. Gupta, M., Kaur, G. Withania somnifera (L.) dunal ameliorates neurodegeneration and cognitive impairments associated with systemic inflammation. BMC Complement. Altern Med. 2019;19 (1): 217.

19. Ahmad, M., Saleem, S., Ahmad, A.S., Ansari, M.A., Yousuf, S., Hoda, M.N., et al., Neuroprotective effects of Withania somnifera on 6-hydroxydopamine induced Parkinsonism in rats. Hum Exp Toxicol. 2005; 24:137-147.

20. Vareed, S.K., Bauer, A.K., Nair, K.M., Li, Y., Jayaprakasam, B., Nair, M.G., et al., Blood-brain barrier permeability of bioactive withanamides present in Withania somnifera fruit extract. Phytother. Res. 2014; 28 (8): 1260-1264.

21. Singh, S., Khanna, D., Kalra, S. Minocycline and Doxycycline: More Than Antibiotics. Curr Mol. Pharmacol. 2021;14(6):1046-1065.

22. Balducci, C., Santamaria, G., La Vitola, P., Brandi, E., Grandi, F., Viscomi, A.R., et al., Doxycycline counteracts neuroinflammation restoring memory in Alzheimer's disease mouse models. Neurobiol Aging. 2018;70:128-139.

23. Santa-Cecília, F.V., Leite, C.A., Del-Bel, E., Raisman-Vozari, R. The Neuroprotective Effect of Doxycycline on Neurodegenerative Diseases. Neurotox Res. 2019;35(4):981-986.

24. Dornelles, G.L., de Oliveira, J.S., de Almeida, E J. R., Mello, C.B.E. Rodrigues, B.R., da Silva, C. B, et al., Ellagic acid inhibits neuroinflammation and cognitive impairment induced by lipopolysaccharides. Neurochem Res. 2020;45(10):2456-2473.

25. Ardah, M.T., Bharathan, G., Kitada, T., Haque, M.E. Ellagic Acid prevents dopamine neuron degeneration from oxidative stress and neuroinflammation in MPTP model of Parkinson's disease. Biomolecules. 2020; 10(11):1519.

Cite this article

Vishala Epuri, Lavanya Prathap, Venkateshwar Reddy, B. Rajesh, B. Ramesh. Cytoprotective and anti-inflammatory effect of ethanolic extract of Withania somnifera root in combination with doxycycline in rotenone induced cytotoxicity in neuroblastoma cell lines.Biomedicine: 2023; 43(1): 469-476

Views
90
Downloads
22
Citations