Neuroprotective insights into Agave cantala: dual modulation of neuroinflammation and oxidative stress by phytochemicals through integrated in silico and in vitro approaches
DOI:
https://doi.org/10.69857/joapr.v13i4.1202Keywords:
Agave cantala, Neuroinflammation, Oxidative Stress, TNF-α, IL-6, Delphinidin, Antioxidant TherapyAbstract
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.
Downloads
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
How to Cite
Issue
Section
Copyright (c) 2025 P. Thamarai Selvi, R Srinivasan

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.







