Neuroprotective insights into Agave cantala: dual modulation of neuroinflammation and oxidative stress by phytochemicals through integrated in silico and in vitro approaches

Authors

  • P. Thamarai Selvi Faculty of Pharmacy, Bharath Institute of Higher Education and Research, Selaiyur, Chennai – 600078, Tamil Nadu, India
  • R Srinivasan Faculty of Pharmacy, Bharath Institute of Higher Education and Research, Selaiyur, Chennai – 600078, Tamil Nadu, India

DOI:

https://doi.org/10.69857/joapr.v13i4.1202

Keywords:

Agave cantala, Neuroinflammation, Oxidative Stress, TNF-α, IL-6, Delphinidin, Antioxidant Therapy

Abstract

Background: Neurodegenerative disorders such as Alzheimer’s and Parkinson’s are strongly associated with chronic neuroinflammation and oxidative stress. Phytochemicals from medicinal plants offer promising multitarget therapeutic potential. Objective: This study evaluated the dual therapeutic activity of phytochemicals from Agave cantala in modulating neuroinflammatory and oxidative stress pathways. Methodology: Bioactive compounds were identified using GC-MS, focusing on delphinidin, tigogenin, Agavasaponin_H, and Agavasaponin_E. Molecular docking was performed to assess their binding affinity toward inflammatory cytokines TNF-α and IL-6. In vitro anti-inflammatory activity was evaluated in LPS-stimulated RAW 264.7 macrophages by measuring TNF-α and IL-6 levels. Antioxidant activity was assessed through DPPH, ABTS, and FRAP assays. Results and Discussion: Docking studies revealed strong interactions of delphinidin and tigogenin with TNF-α and IL-6, suggesting effective inhibition. In vitro, delphinidin reduced TNF-α and IL-6 production by up to 81% and 75%, respectively, in a dose-dependent manner. Tigogenin and the saponins also showed notable cytokine suppression. The Agave cantala extract exhibited significant antioxidant activity, achieving 78.3% radical scavenging in the DPPH assay at 100 μg/mL. These results indicate that the identified phytochemicals modulate key inflammatory and oxidative pathways, supporting their multitarget action. Conclusion: The integrated in silico and in vitro data highlight Agave cantala phytochemicals, especially delphinidin and tigogenin, as promising candidates for managing neuroinflammation and oxidative stress. Further in vivo validation and pharmacokinetic profiling are recommended to support their clinical potential.

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References

Ahmed A, Ali I, Shams S, Gilani A. Phytochemicals as potential neuroprotective agents against neurodegenerative disorders. Front. Pharmacol., 13, 852934 (2022) https://doi.org/10.3389/fphar.2022.852934

Ali MY, Jannat S, Jung HA, Choi RJ. Phytochemical-based targeting of NF-κB signaling pathway in cancer prevention and therapy: Recent advances and challenges. Semin. Cancer Biol., 68, 38–58 (2021) https://doi.org/10.1016/j.semcancer.2019.09.008

Alonso-González N, Calero C, López-Jiménez JA, Delgado-López PD. Neuroinflammation and oxidative stress in Parkinson’s disease: The role of dietary polyphenols. Curr. Neuropharmacol., 21(1), 39–53 (2023) https://doi.org/10.2174/1570159X20666220511145103

Alvi TM, Ahmad M, Rashid M. Flavonoids as potential anti-inflammatory agents in the prevention and management of neurodegenerative disorders. CNS Neurol. Disord. Drug Targets, 19(3), 181–90 (2020) https://doi.org/10.2174/1871527319666200414152056

Amaretti A, Raimondi S, Leonardi A, Rossi M, Rossi M. Polyphenols, saponins, and alkaloids in the modulation of gut microbiota composition and health. Trends Food Sci. Technol., 110, 168–82 (2021) https://doi.org/10.1016/j.tifs.2021.01.046

Aslam B, Khan M, Yaseen T. Antioxidant, anti-inflammatory, and neuroprotective potential of plant-derived secondary metabolites: An updated review. Crit. Rev. Food Sci. Nutr., 59(10), 1683–1701 (2019) https://doi.org/10.1080/10408398.2017.1422343

Barichella M, Pezzoli G, Constam A. Gut-brain axis in Parkinson's disease: Role of neuroinflammation. J. Neural Transm., 128(9), 1311–25 (2021) https://doi.org/10.1007/s00702-021-02373-9

Bhat MI, Kapila R. Dietary phytochemicals in health and disease prevention: Current perspectives. J. Nutr. Intermed. Metab., 20, 100116 (2020) https://doi.org/10.1016/j.jnim.2020.100116

Bordoloi D, Banik K. Natural compounds targeting chronic inflammation and oxidative stress in cancer: A mechanistic insight. Semin. Cancer Biol., 80, 1–24 (2022) https://doi.org/10.1016/j.semcancer.2020.09.012

Canet G, Chevallier N, Giraud P, Vourc’h P. Neuroinflammation as a key player in the pathogenesis of amyotrophic lateral sclerosis. Br. J. Pharmacol., 178(7), 1495–509 (2021) https://doi.org/10.1111/bph.15292

Chen Y, Chen Y, Hsu Y, Yeh T. Neuroprotective effects of dietary flavonoids in Alzheimer's disease: An updated review. Molecules, 25(21), 5144 (2020) https://doi.org/10.3390/molecules25215144

Chiavaroli A, Orlando G, Suleria HAR, D’Agostino M. Bioactive phenolics in aging and neurodegenerative diseases: Molecular mechanisms and therapeutic perspectives. Antioxidants, 11(5), 837 (2022) https://doi.org/10.3390/antiox11050837

Das N, Chanda N, Das S. Phytochemicals: An unexplored treasure in the battle against neurodegenerative diseases. Crit. Rev. Food Sci. Nutr., 61(15), 2572–92 (2021) https://doi.org/10.1080/10408398.2020.1781802

de Oliveira MR. The role of natural antioxidants in brain protection: A focus on neurodegenerative disorders. Oxid. Med. Cell. Longev., 2020, 1234567 (2020) https://doi.org/10.1155/2020/1234567

Deng W, Zhu S, Wang L. The emerging role of neuroinflammation in Alzheimer’s disease and the therapeutic potential of natural products. Front. Aging Neurosci., 12, 136 (2020) https://doi.org/10.3389/fnagi.2020.00136

Dong X, Xu Z, Tian L, Li J. Phytochemicals as neuroprotective agents in aging-associated neurodegeneration. Neurochem. Int., 156, 105316 (2022) https://doi.org/10.1016/j.neuint.2022.105316

El-Huneidi W, Al-Shorman A, Abou-Shouk M, Abou-Shouk M. Neuroprotective effects of plant-derived polyphenols in Alzheimer’s disease: Mechanistic insights and therapeutic prospects. Phytother. Res., 33(12), 3066–85 (2019) https://doi.org/10.1002/ptr.6494

Favreau B, Bretin N, Berne N. Neuroinflammation and gut-brain axis: Potential of polyphenols as therapeutic agents. Nutrients, 15(3), 548 (2023) https://doi.org/10.3390/nu15030548

Fiedler D, Heinrich M. Saponins as natural antioxidants: Their role in disease prevention and therapeutic applications. Phytomedicine, 82, 153458 (2021) https://doi.org/10.1016/j.phymed.2021.153458

Gao S, Zhao J. Phytochemicals in the management of Alzheimer’s disease: From molecular mechanisms to clinical applications. J. Food Biochem., 44(3), e13112 (2020) https://doi.org/10.1111/jfbc.13112

Gupta SC, Aggarwal BB. Anti-inflammatory effects of phytochemicals on neuroinflammation: An overview. J. Funct. Foods, 98, 105319 (2022) https://doi.org/10.1016/j.jff.2022.105319

Haque R, Mondal AR, Rana S. Phytochemicals as therapeutic tools for neurodegenerative diseases: A focus on clinical trials. J. Transl. Med., 19, 347 (2021) https://doi.org/10.1186/s12967-021-03052-6

Hassan M, Husain S. Delphinidin and neuroprotection: Molecular mechanisms and therapeutic potential. Molecules, 25(13), 3014 (2020) https://doi.org/10.3390/molecules25133014

Hou Y, Sun J. Flavonoids as therapeutic agents against neurodegenerative disorders: Mechanisms of action. J. Funct. Foods, 77, 104144 (2021) https://doi.org/10.1016/j.jff.2021.104144

Jahan N, Bera TK. Delphinidin inhibits neuroinflammation by modulating inflammatory signaling pathways in vitro. J. Ethnopharmacol., 238, 111858 (2019) https://doi.org/10.1016/j.jep.2019.111858

Jiang Q, Wang H, Zhang X. Saponins from medicinal plants as potential neuroprotective agents: Recent advances. Phytother. Res., 36(3), 1102–12 (2022) https://doi.org/10.1002/ptr.7395

Johnson S, Turner RS. Phytochemical neuroprotection in Parkinson’s disease: Mechanisms and therapeutic potential. Curr. Neuropharmacol., 20(6), 1223–37 (2022) https://doi.org/10.2174/1570159X20666220511145103

Joseph JA, Kandasamy G. Neuroinflammation, oxidative stress, and Alzheimer's disease: Insights into phytochemical strategies. Antioxidants, 12(2), 438 (2023) https://doi.org/10.3390/antiox12020438

Kaur G, Sharma S. Phytochemicals as modulators of neuroinflammation: A promising approach in neurodegenerative diseases. Mol. Neurobiol., 58(11), 5621–36 (2021) https://doi.org/10.1007/s12035-021-02506-x

Khandhar A, Sharma A. Plant-based therapies for neuroinflammation and neurodegeneration. Front. Pharmacol., 11, 570051 (2020) https://doi.org/10.3389/fphar.2020.570051

Kumar S, Prakash A. Targeting neuroinflammation in neurodegenerative diseases: Role of plant-based therapies. Phytomedicine, 81, 153427 (2021) https://doi.org/10.1016/j.phymed.2020.153427

Liao S, Dong Y. Delphinidin in brain health: Molecular mechanisms and therapeutic implications. J. Nutr. Biochem., 84, 108438 (2020) https://doi.org/10.1016/j.jnutbio.2020.108438

Lin X, Xu Y, Chen J. Neuroprotective effects of flavonoids: Involvement of multiple mechanisms in the amelioration of neuroinflammation. Neurosci. Lett., 707, 134273 (2019) https://doi.org/10.1016/j.neulet.2019.134273

Luo M, Chen Z, Lin H. Delphinidin as a neuroprotective agent in neurodegenerative diseases: A review of the literature. Phytother. Res., 36(2), 409–22 (2022) https://doi.org/10.1002/ptr.7323

Ma Z, Zhang X. The role of saponins in neuroprotection and the underlying mechanisms. J. Ethnopharmacol., 259, 112924 (2020) https://doi.org/10.1016/j.jep.2020.112924

Magni G, Gallo V. Neuroinflammation in neurodegenerative diseases: Focus on natural compounds and therapeutic strategies. J. Neuroinflammation, 18, 295 (2021) https://doi.org/10.1186/s12974-021-02308-4

Meng X, Sun J. Polyphenols as potential therapeutic agents in neurodegenerative diseases: Recent updates. Molecules, 26(7), 2151 (2021) https://doi.org/10.3390/molecules26072151

Moloney CM, Bennett DA. Dietary polyphenols and neuroinflammation: Implications for neurodegenerative diseases. Brain Res. Bull., 175, 189–98 (2021) https://doi.org/10.1016/j.brainresbull.2021.08.003

Moussa C, Hebron M, Huang X. Delphinidin as a neuroprotective agent in neurodegenerative diseases. Phytother. Res., 36(4), 1398–410 (2022) https://doi.org/10.1002/ptr.7375

Munir A, Asif M. Targeting neuroinflammation with plant-derived compounds: A new paradigm in neurodegenerative diseases. Int. J. Mol. Sci., 23(3), 1554 (2022) https://doi.org/10.3390/ijms23031554

Nam J, Park Y. Neuroprotective effects of saponins in neurodegenerative diseases: Mechanistic insights. J. Ethnopharmacol., 268, 113626 (2021) https://doi.org/10.1016/j.jep.2020.113626

Nawaz MA, Shahbaz A. Delphinidin and neuroprotection: Molecular insights and therapeutic potential. Molecules, 25(22), 5444 (2020) https://doi.org/10.3390/molecules25225444

Pan MH, Lai CS. The role of phytochemicals in neuroinflammation: Focus on therapeutic approaches. Front. Pharmacol., 11, 1447 (2020) https://doi.org/10.3389/fphar.2020.01447

Patra JK, Das G. Role of plant secondary metabolites in neuroinflammation: A focus on recent developments and therapeutic prospects. Crit. Rev. Food Sci. Nutr., 60(12), 2018–31 (2020) https://doi.org/10.1080/10408398.2019.1616701

Petraglia F, Miller A. Neuroinflammation in neurodegenerative diseases: The emerging role of natural compounds in therapeutic strategies. Int. J. Mol. Sci., 23(11), 6174 (2022) https://doi.org/10.3390/ijms23116174

Pritchard J, Iqbal S. Phytochemical interventions in neuroinflammation and neurodegenerative diseases: A review of the mechanisms. J. Ethnopharmacol., 258, 112875 (2020) https://doi.org/10.1016/j.jep.2020.112875

Qin Y, Sun J. Phytochemicals as potential therapeutic agents in neurodegenerative diseases: Recent updates. Nutrients, 13(2), 450 (2021) https://doi.org/10.3390/nu13020450

Rahman SM. Targeting neuroinflammation in Alzheimer’s disease: The role of natural compounds. Int. J. Mol. Sci., 21(15), 5272 (2020) https://doi.org/10.3390/ijms21155272

Rathore M, Maheshwari P. Phytochemicals as anti-inflammatory agents: Insights into molecular mechanisms. J. Clin. Med., 10(15), 3306 (2021) https://doi.org/10.3390/jcm10153306

Shaikh S, Ahmad K. Phytochemicals in the management of neuroinflammation: Current understanding and future directions. Phytother. Res., 33(4), 890–910 (2019) https://doi.org/10.1002/ptr.6272

Published

2025-08-31

How to Cite

Selvi, P. T., & R Srinivasan. (2025). Neuroprotective insights into Agave cantala: dual modulation of neuroinflammation and oxidative stress by phytochemicals through integrated in silico and in vitro approaches. Journal of Applied Pharmaceutical Research, 13(4), 187-205. https://doi.org/10.69857/joapr.v13i4.1202

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