Multimodal neuroprotection by Terminalia chebula fruit extract against haloperidol-induced neurotoxicity in rats

Arbind Kumar Choudhary; Ekambaram Manivannan; Kothai Ramalingam; Sathiyendran Kathiravan; Lakshmana Madhan; V Sivasankari; Arul Balasubramanian

doi:10.52756/ijerr.2023.v32.004

Authors

Arbind Kumar Choudhary Govt Erode Medical College, Tamil Nadu, India https://orcid.org/0000-0001-8910-1745
Ekambaram Manivannan Department of Pharmacology, Vinayaka Mission’s College of Pharmacy (VMCP), Yercaud, Salem, Tamil Nadu, India
Kothai Ramalingam Department of Pharmacology, Vinayaka Mission’s College of Pharmacy (VMCP), Yercaud, Salem, Tamil Nadu, India
Sathiyendran Kathiravan Department of Biotechnology, Rajalakshmi Engineering College, Kilpauk, Chennai, India
Lakshmana Madhan Department of Pharmacology, Coimbatore Medical College, Coimbatore, India
V Sivasankari Department of Pharmacology, Vinayaka Mission’s Kirupananda Variyar Medical, College and Hospitals, Salem, Tamil Nadu, India
Arul Balasubramanian Department of Pharmacy Practice, Vinayaka Mission & College of Pharmacy, Salem, Tamil Nadu, India

DOI:

https://doi.org/10.52756/ijerr.2023.v32.004

Keywords:

Catalepsy, Haloperidol, Neurotoxicity, Neurodegenerative, Terminalia chebula

Abstract

Terminalia chebula is a plant with a long history of use in traditional medicine for its medicinal properties. In this study, we investigated the potential neuroprotective effects of an aqueous extract derived from the dried fruit pulp of Terminalia chebula against haloperidol-induced neurotoxicity in Wistar albino rats. Haloperidol is an antipsychotic drug that is known to cause neurotoxicity. In this study, haloperidol-treated rats exhibited behavioral disruptions, oxidative stress, and inflammation. Treatment with the aqueous extract of Terminalia chebula significantly improved these outcomes. The aqueous extract of Terminalia chebula exhibited antioxidant and anti-inflammatory properties. It also protected neuronal architecture. These results suggest that Terminalia chebula may be a potential therapeutic agent for mitigating drug-induced neurotoxicity. The aqueous extract of Terminalia chebula may exert its neuroprotective effects through multiple mechanisms. First, it may act as an antioxidant by scavenging free radicals and reducing oxidative stress. Second, it may have anti-inflammatory properties by suppressing the production of pro-inflammatory cytokines. Third, it may protect neuronal architecture by promoting the growth and repair of neurons. Studies are warranted to elucidate the underlying mechanisms of action of Terminalia chebula and to translate these findings into clinical applications. In particular, it would be interesting to investigate the effects of Terminalia chebula in humans with drug-induced neurotoxicity.

References

A, J., Aarli, Dua, T., Janca, A., & Muscetta, A. (n.d.). NEUROLOGICAL DISORDERS public health challenges, pp. 1–213. https://apps.who.int/iris/bitstream/handle/10665/43605/9241563362_eng.pdf

Chen, H. S., Yung Kang Shen, Lin, C. C., Juan, C. W., Chang, C.Y., & Liang, S. Y. (2022). Ethanol-Soluble Extract of Terminalia chebula Attenuates Paraquat-Induced Apoptosis in PC12 Cells. Current Topics in Nutraceutical Research, 21(1), 25–30. https://doi.org/10.37290/ctnr2641-452x.21:25-30

Choudhary, A. K., Manivannan, E., Ramalingam, K., Sivasankari, V., Balasubramanian, A., & Rajan, C. (2022). Evaluation of The Antidepressant Properties of Aqueous Extract Terminalia Chebula Fruit Pulp in Wistar Albino Rats. International Journal of Life Science and Pharma Research, 6(12). https://doi.org/10.22376/ijpbs/lpr.2022.12.6.p162-169

Dey, A., & De, J. N. (2015). Neuroprotective therapeutics from botanicals and phytochemicals against Huntington’s disease and related neurodegenerative disorders. Journal of Herbal Medicine, 5(1), 1–19. https://doi.org/10.1016/j.hermed.2015.01.002

G.K., S., Muralidhara, & M. S. Bharath, M. (2011). Exploring the Role of “Brahmi” (Bacopa monnieri and Centella asiatica) in Brain Function and Therapy. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 5(1), 33–49. https://doi.org/10.2174/187221411794351833

Geberemeskel, G. A., Debebe, Y. G., & Nguse, N. A. (2019). Antidiabetic Effect of Fenugreek Seed Powder Solution (Trigonella foenum-graecum L.) on Hyperlipidemia in Diabetic Patients. Journal of Diabetes Research, 2019, 1–8. https://doi.org/10.1155/2019/8507453

Grandjean, P., & Landrigan, P. J. (2014). Neurobehavioural effects of developmental toxicity. The Lancet Neurology, 13(3), 330–338. https://doi.org/10.1016/s1474-4422(13)70278-3

Habibi, E., Hossein Bakhshi Jouybari, Reza Valadan, Fatemeh Mirzaee, & Faride Bargi Karizno. (2023). Immunomodulatory activity of polysaccharide from Trametes gibbosa (Pers.) Fr (Basidiomycota, Fungi) mediated by TLR4 signaling pathway. Advanced Biomedical Research, 12(1), 127–127. https://doi.org/10.4103/abr.abr_50_22

Kesharwani, A., Polachira, S. K., Nair, R., Agarwal, A., Mishra, N. N., & Gupta, S. K. (2017). Anti-HSV-2 activity of Terminalia chebula Retz extract and its constituents, chebulagic and chebulinic acids. BMC Complementary and Alternative Medicine, 17(1). https://doi.org/10.1186/s12906-017-1620-8

Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018). Inflammation as a central mechanism in Alzheimer’s disease. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 4(1), 575–590. https://doi.org/10.1016/j.trci.2018.06.014

Landolfo, E., Cutuli, D., Petrosini, L., & Caltagirone, C. (2022). Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans. Biomolecules, 12(5), 667–667. https://doi.org/10.3390/biom12050667

Nigam, M., Mishra, A. P., Adhikari‐Devkota, A., Dirar, A. I., Hassan, Md. M., Adhikari, A., Belwal, T., & Devkota, H. P. (2020). Fruits of Terminalia chebula Retz.: A review on traditional uses, bioactive chemical constituents and pharmacological activities. Phytotherapy Research. 1-16. https://doi.org/10.1002/ptr.6702

Nosalova, G., Jurecek, L., Chatterjee, U. R., Majee, S. K., Nosal, S., & Ray, B. (2013). Antitussive Activity of the Water-Extracted Carbohydrate Polymer from Terminalia chebula on Citric Acid-Induced Cough. Evidence-Based Complementary and Alternative Medicine, 2013, e650134. https://doi.org/10.1155/2013/650134

Olivier, B., Afshari, A. R., Sadeghnia, Hamid R, & Mollazadeh, H. (2016). A Review on Potential Mechanisms of Terminalia chebula in Alzheimer’s Disease. Advances in Pharmacological Sciences, 2016, 8964849. https://doi.org/10.1155/2016/8964849

Pasupuleti, V. R., Arigela, C. S., Gan, S. H., Salam, S. K. N., Krishnan, K. T., Rahman, N. A., & Jeffree, M. S. (2020). A Review on Oxidative Stress, Diabetic Complications, and the Roles of Honey Polyphenols. Oxidative Medicine and Cellular Longevity, 2020, 1–16. https://doi.org/10.1155/2020/8878172

Rao, N. K., & Nammi, S. (2006). Antidiabetic and renoprotective effects of the chloroform extract of Terminalia chebula Retz. seeds in streptozotocin-induced diabetic rats. BMC Complementary and Alternative Medicine, 6, 17. https://doi.org/10.1186/1472-6882-6-17

Ravi Shankara, B., Dhananjaya, B., Ramachandra, Y., Rajan, Ss., Sujan Ganapathy, P., Yarla, N., & Richard, S. (2016). Evaluating the anticancer potential of ethanolic gall extract of Terminalia chebula (Gaertn.) Retz. (combretaceae). Pharmacognosy Research, 8(3), 209. https://doi.org/10.4103/0974-8490.182919

Saini, A., Sawant, L., Sultan Zahiruddin, Dhiraj Shrivastva, Mitra, R., Kumar, R., & Ahmad, S. (2023). LC-MS/MS-based Targeted Metabolomic Profiling of Aqueous and Hydro-alcoholic Extracts of Pistacia integerrima Linn., Quercus infectoria Olivier and Terminalia chebula Retz. Pharmacognosy Magazine, 19(2), 222–230. https://doi.org/10.1177/09731296221144809

Seeman, P., & Kapur, S. (2000). Schizophrenia: More dopamine, more D2 receptors. Proceedings of the National Academy of Sciences, 97(14), 7673–7675. https://doi.org/10.1073/pnas.97.14.7673

Tiwari, R., Mohammed Naseeruddin Inamdar, Raha Orfali, Alshehri, Alghamdi, A., Almadani, M. E., Sultan Alshehri, Syed Imam Rabbani, & Basheeruddin, M. (2023). Comparative evaluation of the potential anti-spasmodic activity of Piper longum, Piper nigrum, Terminalia bellerica, Terminalia chebula, and Zingiber officinale in experimental animals. Journal of the Saudi Pharmaceutical Society, 31(9), 101705–101705. https://doi.org/10.1016/j.jsps.2023.101705

Vassar, R., & Kandalepas, P. C. (2011). The β-secretase enzyme BACE1 as a therapeutic target for Alzheimer’s disease. Alzheimer’s Research & Therapy, 3(3), 20. https://doi.org/10.1186/alzrt82

Yogeswaran Lokanathan, Omar, N., Puzi, A., Aminuddin Bin Saim, & Ruszymah Bt Hj Idrus. (2016). Recent Updates in Neuroprotective and Neuroregenerative Potential of Centella asiatica. PubMed, 23(1), 4–14.

Zhang, X., Qiao, Y. J., Zhu, H., Kong, Q., Ben Zhong Tang, Yang, C. R., & Zhang, Y. J. (2021). Multiple in vitro biological effects of phenolic compounds from Terminalia chebula var. tomentella. Journal of Ethnopharmacology, 275, 114135–114135. https://doi.org/10.1016/j.jep.2021.114135