SYNERGISTIC DUAL PHYTOSOMAL FORMULATION OF RESVERATROL AND SYRINGIC ACID FOR ENHANCED NEUROPROTECTION IN MPTP-INDUCED PARKINSON’S DISEASE
DOI:
https://doi.org/10.22159/ijap.2026v18i3.57346Keywords:
Dopamine, Dual phytosome, MPTP model. Neuroprotection, Parkinson’s disease, Resveratrol, Syringic acid and serotoninAbstract
Objective: Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder characterized by dopaminergic neuronal loss, oxidative stress, and neurotransmitter imbalance. Although L-Dopa remains the standard therapy, its limited efficacy against oxidative damage necessitates alternative strategies. This study aimed to develop and evaluate dual phytosomal formulations of Resveratrol and Syringic acid for synergistic neuroprotective potential in an MPTP-induced Parkinsonian mouse model.
Methods: Mice were divided into control, MPTP, L-Dopa, Resveratrol, Syringic acid, individual phytosomal, and dual phytosomal treatment groups. Behavioral studies, biochemical assays (dopamine and serotonin estimation), in vivo antioxidant analyses (lipid peroxidation and glutathione levels), and histopathological evaluations of the substantia nigra and striatum were performed to assess neuroprotective efficacy.
Results: Resveratrol and Syringic acid significantly reduced immobility and oxidative stress while partially restoring neurotransmitter levels. Their phytosomal formulations further enhanced these effects. The dual phytosomal formulation exhibited a marked synergistic effect by restoring dopamine and serotonin to near-control levels, reducing lipid peroxidation below control values, and preserving neuronal cytoarchitecture. Behavioral analyses confirmed improved motor coordination and reduced Parkinsonian deficits in the dual phytosome group compared with individual treatments and L-Dopa.
Conclusion: The dual phytosomal formulation of Resveratrol and Syringic acid effectively targeted multiple pathological mechanisms of PD, suggesting a novel and promising therapeutic approach for neuroprotection in Parkinson’s disease.
References
1. Radhakrishnan, Divya M, and Vinay Goyal. “Parkinson's disease: A review.” Neurology India vol. 66,Supplement (2018): S26-S35. doi:10.4103/0028-3886.226451
2. Bloem, Bastiaan R et al. “Parkinson's disease.” Lancet (London, England) vol. 397,10291 (2021): 2284-2303. doi:10.1016/S0140-6736(21)00218-X
3. Imbriani, Paola et al. “Oxidative stress and synaptic dysfunction in rodent models of Parkinson's disease.” Neurobiology of disease vol. 173 (2022): 105851. doi:10.1016/j.nbd.2022.105851
4. Park, Jin-Sung et al. “Mitochondrial Dysfunction in Parkinson's Disease: New Mechanistic Insights and Therapeutic Perspectives.” Current neurology and neuroscience reports vol. 18,5 21. 3 Apr. 2018, doi:10.1007/s11910-018-0829-3
5. Jankovic, Joseph, and Eng King Tan. “Parkinson's disease: etiopathogenesis and treatment.” Journal of neurology, neurosurgery, and psychiatry vol. 91,8 (2020): 795-808. doi:10.1136/jnnp-2019-322338
6. Portela, M., A. Silva, M. Carpena, C. Grosso, M. F. Barroso, A. I. Oliveira, C. Martins, C. Ribeiro, and M. A. Prieto. “Phytosomes-Based Nanocarriers Enhanced with Seaweed Extracts: Overcoming the Blood–Brain Barrier.” Eng Proc, vol. 87, no. 1, 2025, p. 75.
7. Lin, K. L., K. J. Lin, P. W. Wang, J. H. Chuang, H. Y. Lin, and S. D. Chen. “Resveratrol Provides Neuroprotective Effects through Modulation of Mitochondrial Dynamics and ERK1/2 Regulated Autophagy.” Free Radical Research, vol. 52, no. 11–12, 2018, pp. 1371–1386.
8. Frozza, R. L., A. Bernardi, J. B. Hoppe, A. B. Meneghetti, C. Batassini, and C. G. Salbego. “Nanocarriers for Resveratrol Delivery and Neuroprotection in Parkinson’s Disease.” Frontiers in Aging Neuroscience, vol. 15, 2023, p. 1180742.
9. Li, X., Y. Qian, Y. Chen, Y. Pang, M. Mao, and X. Zheng. “Syringic Acid Attenuates Neurotoxicity via ER Stress Modulation in Tauopathies.” Neuropharmacology, vol. 184, 2021, p. 108435.
10. Zhao, Y., M. Dang, W. Zhang, Y. Lei, T. Ramesh, V. P. Veeraraghavan, and X. Hou. “Neuroprotective Effects of Syringic Acid against Aluminium Chloride Induced Oxidative Stress Mediated Neuroinflammation in Rat Model of Alzheimer’s Disease.” Journal of Functional Foods, vol. 71, 2020, p. 104009.
11. Anand, U., et al. “Phytosome-Based Drug Delivery Systems for Herbal Bioactives.” Journal of Drug Delivery Science and Technology, vol. 55, 2020, p. 101389.
12. Dhiman, N., et al. “Recent Advances in Phytosomes for Herbal Bioactives.” Journal of Pharmaceutical Innovation, vol. 17, 2022, pp. 849–861.
13. Bhatia, D., S. Bhatia, P. Shelat, and D. Bhatt. “Phytosomes as a Novel Carrier for Delivery of Phytochemicals: A Comprehensive Review.” Journal of Drug Delivery Science and Technology, vol. 80, 2023, p. 104198.
14. Mushtaq, A., F. Khatoon, M. Anwar, and M. A. Khan. “Development and Characterization of Silymarin Phytosomes: An Approach to Enhance Oral Bioavailability.” Pharmaceutics, vol. 14, no. 8, 2022, p. 1621.
15. Singh, S., S. Jain, M. Khandai, A. Tiwari, and H. Rajak. “Formulation Optimization of Berberine-Loaded Phytosomes Using Box–Behnken Design for Antidiabetic Application.” Current Drug Delivery, vol. 19, no. 6, 2022, pp. 683–695.
16. Zafar, M., M. I. Qadir, G. Rasool, A. Saleem, and I. Khan. “Development and Evaluation of Nasal Phytosomal Vaccine Carrier System for Enhanced Brain Delivery.” Pharmaceutics, vol. 15, no. 2, 2023, p. 500.
17. Gosavi, D. D., A. S. Kamdi, S. M. Kalambe, and P. N. Bohra. “The Spontaneous Motor Activity of Aqueous Extract of Withania Coagulans Fruits in Swiss Albino Mice by Actophotometer.” International Journal of Basic & Clinical Pharmacology, vol. 9, no. 9, 2020, pp. 1440–1443.
18. Abbasi-Maleki, S., Z. Kadhoda, and R. Taghizad-Farid. “The Antidepressant-like Effects of Origanum Majorana Essential Oil on Mice through Monoaminergic Modulation Using the Forced Swimming Test.” Journal of Traditional and Complementary Medicine, vol. 10, no. 4, 2020, pp. 327–335.
19. Casarrubea, M., M. Pierucci, S. Aiello, D. Cassar, G. Deidda, G. Crescimanno, et al. “Effects of Chronic Nicotine on the Temporal Structure of Anxiety-Related Behavior in Rats Tested in Hole-Board.” Progress in Neuro-Psychopharmacology & Biological Psychiatry, vol. 96, 2019, p. 109731.
20. Zhou, L., D. Liu, Z. Xie, D. Deng, G. Shi, J. Zhao, et al. “Electrophysiological Characteristics of Dorsal Raphe Nucleus in Tail Suspension Test.” Frontiers in Behavioral Neuroscience, vol. 16, 2022.
21. Kawai, H., R. Iwadate, T. Ishibashi, N. Kudo, Y. Kawashima, and A. Mitsumoto. “Antidepressants with Different Mechanisms of Action Show Different Chronopharmacological Profiles in the Tail Suspension Test in Mice.” Chronobiology International, vol. 36, no. 9, 2019, pp. 1194–1207.
22. Lubrich, C., P. Giesler, and M. Kipp. “Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm.” International Journal of Molecular Sciences, vol. 23, no. 19, 2022, p. 11342.
23. İnaltekin, A., and Y. Kıvrak. “Evaluation of the Effect of Vortioxetine on Pain Threshold by Hot-Plate Test in Mice.” Nöro Psikiyatri Arşivi, vol. 58, no. 4, 2021, pp. 274–277.
24. Nam, J., C. T. Richie, B. K. Harvey, M. H. Voutilainen, et al. “Delivery of CDNF by AAV-Mediated Gene Transfer Protects Dopamine Neurons in the MPTP Mouse Model of Parkinson’s Disease.” Scientific Reports, vol. 14, 2024, p. 16487.
25. Kolacheva, A., L. Alekperova, E. Pavlova, A. Bannikova, and M. V. Ugrumov. “Changes in Tyrosine Hydroxylase Activity and Dopamine Synthesis in the Nigrostriatal System of Mice in an Acute Model of Parkinson’s Disease as a Manifestation of Neurodegeneration and Neuroplasticity.” Brain Sciences, vol. 12, no. 6, 2022, p. 779.
26. Gopinath, A., M. Ugrumov, E. Pavlova, et al. “DAT and TH Expression Marks Human Parkinson’s Disease Phenotype: MPTP Mouse Model Insights.” NPJ Parkinson’s Disease, vol. 8, 2022, p. 42.
27. Kumar, V., A. Prakash, and N. Kaur. “Quercetin Alleviates Neurotoxicity in Parkinson’s Disease Model via PI3K/Akt/GSK3β Pathway.” Neurochemistry International, vol. 140, 2020, p. 104862.
28. Gupta, S., B. Sharma, and A. Mishra. “Neuroprotective Effect of Berberine against MPTP-Induced Parkinson’s Disease in Mice.” Biomedicine & Pharmacotherapy, vol. 137, 2021, p. 111299.
29. Meredith, G. E., Rademacher, D. J., MPTP mouse models of Parkinson's disease: an update. J Parkinsons Dis. 2011;1(1):19-33. doi: 10.3233/JPD-2011-11023. PMID: 23275799; PMCID: PMC3530193.
30. Buchanan, A. M., Mena, S., Choukari, I. et al. Serotonin as a biomarker of toxin-induced Parkinsonism. Mol Med 30, 33 (2024). https://doi.org/10.1186/s10020-023-00773-9.
31. Kalivani, P., Kamraj, R. Phytosome Technology: A Novel Breakthrough for the Health Challenges. Cureus. 2024 30; 16(8):e68180. doi: 10.7759/cureus.68180. PMID: 39347133.
32. Molaveisi, M., Shahidi, N. M., Karim, P., and Ali, T. R. Fate of Nano-Phytosomes Containing Bioactive Compounds of Echinacea Extract in an Acidic Food Beverage. (2021) Food Structure 27. 100177. 10.1016/j.foostr.2021.100177.
Published
How to Cite
Issue
Section
Copyright (c) 2026 RAMYA KUBER B., JYOTHIRMAYI J., VARALAKSHMI N., MAYURI P. N.
This work is licensed under a Creative Commons Attribution 4.0 International License.