Synergistic effects of Ginkgo biloba and voluntary exercise on oxidative stress and antioxidant markers in Parkinson’s disease in mice model
Subject Areas : Journal of Medicinal Herbs, "J. Med Herb" (Formerly known as Journal of Herbal Drugs or J. Herb Drug)Keivan Mehdipournezhad 1 , Khosro Jalali Dehkordi 2 *
1 - Department of Sport Physiology, Isf.C., Islamic Azad University, Isfahan, Iran;
2 - Department of Sport Physiology, Isf.C., Islamic Azad University, Isfahan, Iran;
Keywords: Parkinson's disease, Ginkgo biloba, SOD, SIRT1, MDA, Voluntary exercise,
Abstract :
Background & Aim: Parkinson's disease (PD) is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons in the substantia nigra. Inflammation and oxidative stress contribute significantly to its progression. This study assessed the effects of voluntary exercise and Ginkgo biloba supplementation on oxidative stress in a PD mouse model, using thirty female C57BL/6 mice induced with PD via MPTP. Experimental: The study included a pre-test and post-test phase with an eight-week intervention. Mice in the exercise group used spinning wheels daily, while those in the Ginkgo biloba group received 80 mg plant extract via gavage. A combination group followed both methods, and a control group received a placebo. Biochemical assessments were conducted after fasting, and results were analyzed with one-way ANOVA. Results: Findings showed that expression levels of SIRT1 and NRF2 as well as SOD concentration were significantly lower (P<0.05) in the PD model compared to control but increased after interventions. Malondialdehyde (MDA) levels were elevated in the PD group but decreased following the interventions, with the greatest improvements in the combination group, indicating a synergistic effect in alleviating Parkinson symptoms. Recommended applications/industries: Complimentary medicine identified Ginkgo biloba and voluntary exercise are recognized as effective methods to prevent and improve neurodegenerative disorder. Based on present results, Ginkgo biloba extract and voluntary exercise improved SIRT1 and NRF2 as well as SOD and MDA concentration in Parkinson condition. Furthermore, consuming the Ginkgo biloba along with voluntary exercise might recover oxidative stress pathway and regulate the hub genes networks.
Abedpoor, N., Taghian, F., Jalali Dehkordi, K. and Safavi, K. 2024. Sparassis latifolia and exercise training as complementary medicine mitigated the 5-fluorouracil potent side effects in mice with colorectal cancer: bioinformatics approaches, novel monitoring pathological metrics, screening signatures, and innovative management tactic. Cancer Cell International, 24(1): 141.
Abedpoor, N., Taghian, F., Jalali Dehkordi, K. and Safavi, K. 2025. The role of Sparasis Latifolia and Aerobic Exercise on Anti-inflammatory Activities and Regulation of Inflammatory Factors in the Intestine of Mice with Colon Cancer Under Chemotherapy. Iranian Journal of Nutrition Sciences and Food Technology, 19(4): 13-24.
Adebayo, O. G., Aduema, W., Emmanuel, M. U., Ben-Azu, B., Orji, B. O., Akpakpan, E., Adebayo, O. R., Onuoha, O. G. and Ajayi, A. M. 2022. The anti-Parkinson potential of gingko biloba-supplement mitigates cortico-cerebellar degeneration and neuropathobiological alterations via inflammatory and apoptotic mediators in mice. Neurochemical Research, 47(8): 2211-2229.
Ahmad, R., Tripathi, A. K., Tripathi, P., Singh, S., Singh, R. and Singh, R. K. 2008. Malondialdehyde and protein carbonyl as biomarkers for oxidative stress and disease progression in patients with chronic myeloid leukemia. In Vivo, 22(4): 525-528.
Biernacka, P., Felisiak, K., Adamska, I., Śnieg, M. and Podsiadło, C. 2023. Effect of brewing conditions on antioxidant properties of Ginkgo biloba leaves infusion. Antioxidants, 12(7): 1455.
Chen, C. M., Lin, C. H., Wu, Y. R., Yen, C.-Y., Huang, Y. T., Lin, J. L., Lin, C. Y., Chen, W. L., Chao, C. Y. and Lee-Chen, G. J. 2020. Lactulose and melibiose inhibit α-synuclein aggregation and up-regulate autophagy to reduce neuronal vulnerability. Cells, 9(5): 1230.
Dauer, W. and Przedborski, S. 2003. Parkinson's disease: mechanisms and models. Neuron, 39(6): 889-909.
Gong, X., Huang, M. and Chen, L. 2024. NRF1 mitigates motor dysfunction and dopamine neuron degeneration in mice with Parkinson's disease by promoting GLRX m6A methylation through upregulation of METTL3 transcription. CNS Neuroscience & Therapeutics, 30(3): e14441.
He, J., Zhu, G., Wang, G. and Zhang, F. 2020. Oxidative stress and neuroinflammation potentiate each other to promote progression of dopamine neurodegeneration. Oxidative Medicine and Cellular Longevity, 2020(1): 6137521.
Jankovic, J. and Lang, A. E. 2021. Diagnosis and assessment of Parkinson disease and other movement disorders. Bradley's Neurology in Clinical Practice E-Book, pp. 311-330.
Lee, K. H., Cha, M. and Lee, B. H. 2020. Neuroprotective effect of antioxidants in the brain. International Journal of Molecular Sciences, 21(19): 7152.
Li, F., Boateng, I. D., Yang, X. M., Li, Y. and Liu, W. 2023. Effects of processing methods on quality, antioxidant capacity, and cytotoxicity of Ginkgo biloba leaf tea product. Journal of the Science of Food and Agriculture, 103(10): 4993-5003.
Liu, H., Ye, M. and Guo, H. 2020. An updated review of randomized clinical trials testing the improvement of cognitive function of Ginkgo biloba extract in healthy people and Alzheimer’s patients. Frontiers in Pharmacology, 10: 509513.
Liu, Q., Wang, J., Gu, Z., Ouyang, T., Gao, H., Kan, H. and Yang, Y. 2024. Comprehensive exploration of the neuroprotective mechanisms of Ginkgo biloba leaves in treating neurological disorders. The American Journal of Chinese Medicine, 52(04): 1053-1086.
Moujalled, D., Strasser, A. and Liddell, J. R. 2021. Molecular mechanisms of cell death in neurological diseases. Cell Death and Differentiation, 28(7): 2029-2044.
Murakami, H., Shiraishi, T., Umehara, T., Omoto, S. and Iguchi, Y. 2023. Recent advances in drug therapy for Parkinson's disease. Internal Medicine, 62(1): 33-42.
Nowak, A., Kojder, K., Zielonka-Brzezicka, J., Wróbel, J., Bosiacki, M., Fabiańska, M., Wróbel, M., Sołek-Pastuszka, J. and Klimowicz, A. 2021. The use of Ginkgo biloba L. as a neuroprotective agent in the Alzheimer’s disease. Frontiers in Pharmacology, 12: 775034.
Rojas, P., Montes, P., Rojas, C., Serrano-García, N. and Rojas-Castañeda, J. C. 2012. Effect of a phytopharmaceutical medicine, Ginko biloba extract 761, in an animal model of Parkinson's disease: Therapeutic perspectives. Nutrition, 28(11-12): 1081-1088.
Ryu, D. W., Lee, S. H., Oh, Y. S., An, J. Y., Park, J. W., Song, I. U. and Kim, J. S. 2017. Clinical characteristics of Parkinson’s disease developed from essential tremor. Journal of Parkinson's disease, 7(2), 369-376.
Safavi, K., Abedpoor, N., Hajibabaie, F. and Kaviani, E. 2025. Mitigating diabetic cardiomyopathy: The synergistic potential of sea buckthorn and metformin explored via bioinformatics and chemoinformatics. Biology, 14(4): 361-366.
Safavi, K., Hajibabaie, F. and Abedpoor, N. 2024. Bioinformatics and chemoinformatics analysis explored the role of Linum usitatissimum in diabetic heart conditions: experimental analysis in H9c2 rat embryonic cardiomyocytes cell lines. Journal of Medical Signals & Sensors, 14(9): 27-32.
Sivanandy, P., Leey, T. C., Xiang, T. C., Ling, T. C., Wey Han, S. A., Semilan, S. L. A. and Hong, P. K. 2021. Systematic review on Parkinson's disease medications, emphasizing on three recently approved drugs to control Parkinson's symptoms. International Journal of Environment Research and Public Health, 19(1): 19010364.
Surendran, S. and Rajasankar, S. 2010. Parkinson’s disease: oxidative stress and therapeutic approaches. Neurological Sciences, 31: 531-540.
Umehara, T., Mimori, M., Kokubu, T., Ozawa, M., Shiraishi, T., Sato, T., Onda, A., Matsuno, H., Omoto, S. and Murakami, H. 2024. Serum phosphorus levels associated with nigrostriatal dopaminergic deficits in drug-naïve Parkinson's disease. Journal of the Neurological Sciences, 464: 123165.
Wang, H., Wu, X., Lezmi, S., Li, Q., Helferich, W. G., Xu, Y. and Chen, H. 2017. Extract of Ginkgo biloba exacerbates liver metastasis in a mouse colon cancer Xenograft model. BMC Complementary and Alternative Medicine, 17: 1-12.
Winiarska-Mieczan, A., Baranowska-Wójcik, E., Kwiecień, M., Grela, E. R., Szwajgier, D., Kwiatkowska, K., and Kiczorowska, B. 2020. The role of dietary antioxidants in the pathogenesis of neurodegenerative diseases and their impact on cerebral oxidoreductive balance. Nutrients, 12(2), 435.
Xiao, F., Kabachkova, A. V., Jiao, L., Zhao, H. and Kapilevich, L. V. 2023. Effects of cold water immersion after exercise on fatigue recovery and exercise performance--meta analysis. Front Physiology, 14: 1006512.
Zang, R., Ling, F., Wu, Z., Sun, J., Yang, L., Lv, Z. and Ji, N. 2023. Ginkgo biloba extract (EGb-761) confers neuroprotection against ischemic stroke by augmenting autophagic/lysosomal signaling pathway. Journal of Neuroimmunology, 382: 578101.
Zaychik, Y., Fainstein, N., Touloumi, O., Goldberg, Y., Hamdi, L., Segal, S., Nabat, H., Zoidou, S., Grigoriadis, N. and Katz, A. 2021. High-intensity exercise training protects the brain against autoimmune neuroinflammation: regulation of microglial redox and pro-inflammatory functions. Frontiers in Cellular Neuroscience, 15: 640724.
Zhang, X., Bai, L., Zhang, S., Zhou, X., Li, Y. and Bai, J. 2018. Trx-1 ameliorates learning and memory deficits in MPTP-induced Parkinson's disease model in mice. Free Radical Biology and Medicine, 124: 380-387.