Therapeutic Potential of Bacopa monnieri L. in Sciatic Nerve Ligation: Modulation of Regeneration and Oxidative Stress

Year 2023, Volume: 3 Issue: 2, 32 - 38, 27.09.2023

Ziadoon Al-yaqoobi Öznur Altunlu Feyza Burul Esma Topatan Behzad Mokhtare Ayşenur Budak Savaş Mehmet Ali Yörük Burak Çınar Selma Sezen Cemil Bayram Irmak Ferah Okkay Ufuk Okkay Ahmet Hacımüftüoğlu

https://doi.org/10.5152/JLASP.2023.23010

Abstract

Bacopa monnieri L. is a plant known for its neuroprotective properties with positive effects on neuronal regeneration and synaptic activity. In this study, the effects of Bacopa monnieri L. extract on the regeneration process in sciatic nerve injury, which is a peripheral nerve injury model, were investigated. Within the scope of this study, 18 Sprague–Dawley rats, each group containing six animals, were divided into three groups. Surgical ligation of the sciatic nerve was performed at the beginning of the experiment to induce sciatic nerve injury in the positive control and treatment groups. Following surgical intervention, the treatment group received a daily dose of 400 mg/kg extract for 15 days starting from the 14th day post surgery. The oxidative stress status in serum samples obtained from rats was investigated biochemically. Immunohistochemical measurements of tumor necrosis factor alpha and inducible nitric oxide synthase were also performed in the muscles surrounding the sciatic nerve. Upon examination of the results, it was observed that the treatment group exhibited a significant increase in antioxidant capacity compared to the control groups. Furthermore, the oxidant status in the treatment group was lower than that in the positive control group. Immunohistochemical examinations revealed an increase in tumor necrosis factor alpha- and inducible nitric oxide synthase immunoreactivity in the positive control group, while a decrease in the immunoreactivity of these inflammation markers was observed in the treatment group. In conclusion, Bacopa monnieri L. extract may contribute to recovery in peripheral nerve injury by regulating antioxidant and anti-inflammatory processes.

Keywords

İmmunohistokimyasal, antioxidant, Bacopa monnieri L., peripheral nerve injury, sciatic nerve ligation

Siyatik Sinir Ligasyonunda Bacopa monnieri L.’nin Tedavi Potansiyeli: Rejenerasyon ve Oksidatif Stresin Modülasyonu

Abstract

Bacopa monnieri L. nöronal rejenerasyon ve sinaptik aktivite üzerinde olumlu etkileri olduğu bilinen nöroprotektif özelliğe sahip bir bitkidir. Bu çalışmada Bacopa monnieri L. ekstresinin periferik sinir hasarı modeli olan siyatik sinir hasarında rejenerasyon süreci üzerine etkileri araştırılmıştır. Çalışma kapsamında Sprague–Dawley ırkı 18 adet sıçan her birinde 6 hayvan bulunan 3 gruba ayrıldı. Pozitif kontrol ve tedavi gruplarına siyatik sinir hasarı oluşturmak amacıyla deneyin başlangıcında cerrahi olarak siyatik sinir ligasyonu uygulandı. Tedavi grubuna cerrahi uygulama sonrası 14. günden itibaren 15 gün boyunca 400 mg/kg/gün ekstrakt uygulandı. Sıçanlardan alınan serum örneklerinde oksidatif stres durumu biyokimyasal olarak araştırıldı. İmmunohistokimyasal olarak ise siyatik sinir çevresindeki kaslarda TNF-α ve iNOS ölçümü gerçekleştirildi. Elde edilen sonuçlar incelendiğinde kontrol gruplarına göre tedavi grubunda antioksidan kapasite önemli ölçüde artmıştır. Oksidan durumun ise tedavi grubunda PC grubundan daha düşük olduğu görülmüştür. Immunohistochemical incelemelerde PC grubunda TNF-α ve iNOS immunoreaktivitesini artarken tedavi grubunda bu inflamasyon belirteçlerinin immunoreaktivitesinin düştüğü belirlenmiştir. Sonuç olarak Bacopa monnieri L. ekstresi periferik sinir hasarında antioksidan ve antiinflamatuar süreçleri düzenleyerek iyileşmeye katkı sağlayabilir.

Keywords

Antiinflamatuar, antioksidan, Bacopa monnieri L., periferik sinir hasarı, siyatik sinir bağlama

References

• 1. Allodi, I., Udina, E., & Navarro, X. (2012). Specificity of peripheral nerve regeneration: Interactions at the axon level. Progress in Neurobiology, 98(1), 16–37. [CrossRef]
• 2. An, Y., Yan, H. X., Zhao, J. N., Yang, X. M., & Yan, J. T. (2022). Evaluation methods of a rat sciatic nerve crush injury model. Journal of Integrative Neuroscience, 21(3), 91. [CrossRef]
• 3. Bhardwaj, P., Goswami, N., Narula, P., Jain, C. K., & Mathur, A. (2018). Zinc oxide nanoparticles (ZnO NP) mediated regulation of bacosides biosynthesis and transcriptional correlation of HMG-CoA reductase gene in suspension culture of Bacopa monnieri. Plant Physiology and Biochemistry, 130, 148–156. [CrossRef]
• 4. Deepak, M., & Amit, A. (2013). ‘Bacoside B’ — The need remains for establishing identity. Fitoterapia, 87, 7–10. [CrossRef]
• 5. Dong, R., Liu, Y., Yang, Y., Wang, H., Xu, Y., & Zhang, Z. (2019). MSC-derived exosomes-based therapy for peripheral nerve injury: A novel therapeutic strategy. BioMed Research International, 2019, 6458237. [CrossRef]
• 6. Dowell, A., Davidson, G., & Ghosh, D. (2015). Validation of quantitative HPLC method for bacosides in KeenMind. Evidence-Based Complementary and Alternative Medicine: eCAM, 2015, 696172. [CrossRef]
• 7. Emsen, B., Karataş, M., & Doğan, M. (2019). In vitro Koşullarda Çoğaltılan Bacopa monnieri L. Pennell’nin Oksidatif Stres İnhibisyon Aktiviteleri. Karaelmas Fen ve Mühendislik Dergisi, 9(2), 181–189.
• 8. Ferah Okkay, I., Okkay, U., Bayram, C., Cicek, B., Sezen, S., Aydin, I. C., Mendil, A. S., & Hacimuftuoglu, A. (2023). Bromelain protects against cisplatin-induced ocular toxicity through mitigating oxidative stress and inflammation. Drug and Chemical Toxicology, 46(1), 69–76. [CrossRef]
• 9. Ferdowsi, S., Abdolmaleki, A., Asadi, A., & Zahri, S. (2023). Effect of azithromycin on sciatic nerve injury in the Wistar rats. Neurochemical Research, 48(1), 161–171. [CrossRef]
• 10. Jauhari, N., Bharadwaj, R., Sharma, N., & Bharadvaja, N. (2019). Assessment of bacoside production, total phenol content and antioxidant potential of elicited and non-elicited shoot cultures of Bacopa monnieri (L.). Environmental Sustainability, 2(4), 441–453. [CrossRef]
• 11. Jeyasri, R., Muthuramalingam, P., Adarshan, S., Shin, H., & Ramesh, M. (2022). Assessing the anti-inflammatory effects of bacopa-derived bioactive compounds using network pharmacology and in vitro studies. ACS Omega, 7(44), 40344–40354. [CrossRef]
• 12. Jeyasri, R., Muthuramalingam, P., Suba, V., Ramesh, M., & Chen, J. T. (2020). Bacopa monnieri and their bioactive compounds inferred multitarget treatment strategy for neurological diseases: A cheminformatics and system pharmacology approach. Biomolecules, 10(4), 536. [CrossRef]
• 13. Kiguchi, N., Kobayashi, Y., Saika, F., Sakaguchi, H., Maeda, T., & Kishioka, S. (2015). Peripheral interleukin-4 ameliorates inflammatory macrophage-dependent neuropathic pain. Pain, 156(4), 684–693. [CrossRef]
• 14. Kishore, L., Kaur, N., & Singh, R. (2016). Renoprotective effect of Bacopa monnieri via inhibition of advanced glycation end products and oxidative stress in STZ-nicotinamide-induced diabetic nephropathy. Renal Failure, 38(9), 1528–1544. [CrossRef]
• 15. Kishore, L., Kaur, N., & Singh, R. (2017). Bacosine isolated from aerial parts of Bacopa monnieri improves the neuronal dysfunction in streptozotocin-induced diabetic neuropathy. Journal of Functional Foods, 34, 237–247. [CrossRef]
• 16. Kornfeld, T., Vogt, P. M., & Radtke, C. (2019). Nerve grafting for peripheral nerve injuries with extended defect sizes [Nerventransplantate für periphere Nervenverletzungen ausgedehnterer Defektgrößen]. Wiener Medizinische Wochenschrift, 169(9–10), 240–251. [CrossRef]
• 17. Lopes, B., Sousa, P., Alvites, R., Branquinho, M., Sousa, A. C., Mendonça, C., Atayde, L. M., Luís, A. L., Varejão, A. S. P., & Maurício, A. C. (2022). Peripheral nerve injury treatments and advances: One health perspective. International Journal of Molecular Sciences, 23(2). [CrossRef]
• 18. Mehta, J., Utkarsh, K., Fuloria, S., Singh, T., Sekar, M., Salaria, D., Rolta, R., Begum, M. Y., Gan, S. H., Rani, N. N. I. M., Chidambaram, K., Subramaniyan, V., Sathasivam, K. V., Lum, P. T., Uthirapathy, S., Fadare, O. A., Awofisayo, O., & Fuloria, N. K. (2022). Antibacterial potential of Bacopa monnieri (L.) Wettst. and its bioactive molecules against uropathogens–An in silico study to identify potential lead molecule(s) for the development of new drugs to treat urinary tract infections. Molecules, 27(15), 4971. [CrossRef]
• 19. Nadeau, S., Filali, M., Zhang, J., Kerr, B. J., Rivest, S., Soulet, D., Iwakura, Y., de Rivero Vaccari, J. P., Keane, R. W., & Lacroix, S. (2011). Functional recovery after peripheral nerve injury is dependent on the proinflammatory cytokines IL-1β and TNF: Implications for neuropathic pain. Journal of Neuroscience, 31(35), 12533–12542. [CrossRef]
• 20. Nemetchek, M. D., Stierle, A. A., Stierle, D. B., & Lurie, D. I. (2017). The Ayurvedic plant Bacopa monnieri inhibits inflammatory pathways in the brain. Journal of Ethnopharmacology, 197, 92–100. [CrossRef]
• 21. Ohtori, S., Takahashi, K., Moriya, H., & Myers, R. R. (2004). TNF-alpha and TNF-alpha receptor type 1 upregulation in glia and neurons after peripheral nerve injury: Studies in murine DRG and spinal cord. Spine (Phila Pa 1976), 29(10), 1082–1088. [CrossRef]
• 22. Okkay, U., Ferah Okkay, I., Cicek, B., Aydin, I. C., Ertugrul, M. S., Bayram, C., Senyayla, S., Sezen, S., Mendil, A. S., Guven, L., & Hacimuftuoglu, A. (2021). Achillea millefolium alleviates testicular damage in paclitaxel intoxicated rats via attenuation of testicular oxido-inflammatory stress and apoptotic responses. Andrologia, 53(5), e14028. [CrossRef]
• 23. Omura, T., Sano, M., Omura, K., Hasegawa, T., Doi, M., Sawada, T., & Nagano, A. (2005). Different expressions of BDNF, NT3, and NT4 in muscle and nerve after various types of peripheral nerve injuries. Journal of the Peripheral Nervous System, 10(3), 293–300. [CrossRef]
• 24. Qian, Y., Han, Q., Zhao, X., Song, J., Cheng, Y., Fang, Z., Ouyang, Y., Yuan, W. E., & Fan, C. (2018). 3D melatonin nerve scaffold reduces oxidative stress and inflammation and increases autophagy in peripheral nerve regeneration. Journal of Pineal Research, 65(4), e12516. [CrossRef]
• 25. Rayner, M. L. D., Day, A. G. E., Bhangra, K. S., Sinden, J., & Phillips, J. B. (2021). Engineered neural tissue made using clinical-grade human neural stem cells supports regeneration in a long gap peripheral nerve injury model. Acta Biomaterialia, 135, 203–213. [CrossRef]
• 26. Rayner, M. L. D., Grillo, A., Williams, G. R., Tawfik, E., Zhang, T., Volitaki, C., Craig, D. Q. M., Healy, J., & Phillips, J. B. (2020). Controlled local release of PPARγ agonists from biomaterials to treat peripheral nerve injury. Journal of Neural Engineering, 17(4), 046030. [CrossRef]
• 27. Ren, W. J., Liu, Y., Zhou, L. J., Li, W., Zhong, Y., Pang, R. P., Xin, W. J., Wei, X. H., Wang, J., Zhu, H. Q., Wu, C. Y., Qin, Z. H., Liu, G., & Liu, X. G. (2011). Peripheral nerve injury leads to working memory deficits and dysfunction of the hippocampus by upregulation of TNF-α in rodents. Neuropsychopharmacology, 36(5), 979–992. [CrossRef]
• 28. Sanyal, R., Nandi, S., Pandey, S., Chatterjee, U., Mishra, T., Datta, S., Prasanth, D. A., Anand, U., Mane, A. B., Kant, N., Jha, N. K., Jha, S. K., Shekhawat, M. S., Pandey, D. K., & Dey, A. (2022). Biotechnology for propagation and secondary metabolite production in Bacopa monnieri. Applied Microbiology and Biotechnology, 106(5–6), 1837–1854. [CrossRef]
• 29. Savastano, L. E., Laurito, S. R., Fitt, M. R., Rasmussen, J. A., Gonzalez Polo, V., & Patterson, S. I. (2014). Sciatic nerve injury: A simple and subtle model for investigating many aspects of nervous system damage and recovery. Journal of Neuroscience Methods, 227, 166–180. [CrossRef]
• 30. Shahid, M., Subhan, F., Ahmad, N., & Ullah, I. (2017). A bacosides containing Bacopa monnieri extract alleviates allodynia and hyperalgesia in the chronic constriction injury model of neuropathic pain in rats. BMC Complementary and Alternative Medicine, 17(1), 293. [CrossRef]
• 31. Shinomol, G. K., Muralidhara, & Bharath, M. M. (2011). Exploring the role of “Brahmi” (Bacopa monnieri and Centella asiatica) in brain function and therapy. Recent Patents on Endocrine, Metabolic and Immune Drug Discovery, 5(1), 33–49. [CrossRef]
• 32. Siemionow, M., & Brzezicki, G. (2009). Chapter 8 current techniques and concepts in peripheral nerve repair. In International review of neurobiology (Vol. 87, pp. 141–172). Academic Press. [CrossRef]
• 33. Slavin, B. R., Sarhane, K. A., von Guionneau, N., Hanwright, P. J., Qiu, C., Mao, H. Q., Höke, A., & Tuffaha, S. H. (2021). Insulin-like growth Factor-1: A promising therapeutic target for peripheral nerve injury. Frontiers in Bioengineering and Biotechnology, 9, 695850. [CrossRef]
• 34. Starinets, A., Tyrtyshnaia, A., & Manzhulo, I. (2023). Anti-inflammatory activity of synaptamide in the peripheral nervous system in a model of sciatic nerve injury. International Journal of Molecular Sciences, 24(7), 6273. [CrossRef]
• 35. Toraman, E., Bayram, C., Sezen, S., Özkaraca, M., Hacımüftüoğlu, A., & Budak, H. (2023). Parthenolide as a potential analgesic in the treatment of paclitaxel-induced neuropathic pain: The rat modeling. Naunyn-Schmiedeberg’s Archives of Pharmacology. [CrossRef]
• 36. Vecchiarelli, H. A., & Tremblay, M.-È. (2023). Microglial transcriptional signatures in the central nervous system: Toward a future of unraveling their function in health and disease. Annual Review of Genetics, 57(1). [CrossRef]
• 37. Vigneshwar, R., Arivalagan, A., & Palanivel, M. (2021). Thyrogenic, hypolipidemic and antioxidant effects of Bacopa monnieri (Brahmi) on experimental hypothyroidism in rats. Journal of Pharmacognosy and Phytochemistry, 10(1), 454–458.
• 38. Wang, H., Ding, X. G., Li, S. W., Zheng, H., Zheng, X. M., Navin, S., Li, L., & Wang, X. H. (2015). Role of oxidative stress in surgical cavernous nerve injury in a rat model. Journal of Neuroscience Research, 93(6), 922–929. [CrossRef]
• 39. Wang, M. L., Rivlin, M., Graham, J. G., & Beredjiklian, P. K. (2019). Peripheral nerve injury, scarring, and recovery. Connective Tissue Research, 60(1), 3–9. [CrossRef]
• 40. Wang, Y., Wehling-Henricks, M., Samengo, G., & Tidball, J. G. (2015). Increases of M2a macrophages and fibrosis in aging muscle are influenced by bone marrow aging and negatively regulated by mus cle-derived nitric oxide. Aging Cell, 14(4), 678–688. [CrossRef]
• 41. Xiaoting, L., Ding, Y., Zhang, Y., Tse, H., & Lian, Q. (2013). Paracrine mechanisms of mesenchymal stem cell-based therapy: Current status and perspectives. Cell Transplantation, 23(9), 1045–1059. [CrossRef]
• 42. Zhang, L., Johnson, D., & Johnson, J. A. (2013). Deletion of Nrf2 impairs functional recovery, reduces clearance of myelin debris and decreases axonal remyelination after peripheral nerve injury. Neurobiology of Disease, 54, 329–338. [CrossRef]
• 43. Zhang, M., Li, L., An, H., Zhang, P., & Liu, P. (2021). Repair of peripheral nerve injury using hydrogels based on self-assembled peptides. Gels, 7(4). [CrossRef]