The Effectiveness of Centella asiatica Extract and Aerobic Exercise on Plasma Levels of Amyloid Beta-42 and Phosphorylated Tau in Older Women with Dementia

Year 2024, , 1156 - 1162, 25.09.2024

Lisna Anisa Fitriana , I Ketut Adnyana , Kusnandar Anggadiredja , Iwan Setiawan , Ria Maria Theresa Puu Taa Luu

https://doi.org/10.33438/ijdshs.1505669

Abstract

Urgency: Effect of Centella asiatica (CA) and aerobic exercise on Amyloid beta-42 (Aβ42) and phosphorylated tau (p-tau) as biomarkers of dementia is not yet known. Objectives: This study aimed to analyze the effect of CA, aerobic exercise, and their combination on Aβ42 and p-tau in older women with dementia. Design: It was a 24-week randomized, double-blind controlled trial. Partisipant: Subjects were divided into four groups: the Centella asiatica group (CA, 1x500 mg/day, n = 16), the aerobic exercise group (AE, 3x60 minutes/week, n = 16), the CA-AE combination group (1x500 mg/day and exercise, n = 15), and the placebo group (n = 15). Instruments: The dementia screening test used the Mini Mental State Examination (Intraclass correlation coefficients : ranging from 0.60 to 0.93, sensitivity of 88.3%) and Clinical Dementia Rating questionnaires (sensitivity 93.6% and specificity 100%). The Wilcoxon, Kruskal-Wallis, and Mann-Whitney tests were used to analyze the data. Results: Plasma amyloid beta-42 showed an increase in all groups: CA (p<0.001), AE (p=0.001), CA-AE combination (p<0.001), and placebo (p<0.001). Meanwhile, plasma p-tau also decreased in CA (p<0.001), AE (p<0.001), and CA-AE combination (p=0.001). The Mann-Whitney test showed that Centella asiatica caused the highest increase in Aβ42 (∆=233.5; p<0.001). Conclusion: This study indicate that Centella asiatica, aerobic exercise, and the CA-AE combination were effective in improving plasma Aβ42 and decreasing p-tau in older women with dementia. Contributions: This study can be an alternative therapy for the prevention and treatment of cognitive decline. Research with a larger sample size is recommended.

Keywords

Amyloid-Beta, Centella Asiatica, Dementia, Exercise, P-tau

References

• Burhaein, E., Demirci, N.,Diajeng Tyas Pinru Phytanza, D.T.P.,Nadzalan, A., And Niksic, E. (2024). Is Walking a Miracle Cure for Active and Healthy Aging?. Int. J. Act. Health Aging, 2(1),10-17. [CrossRef]
• Cancela, J. M., Vila Suárez, M. H., Vasconcelos, J., Lima, A., & Ayán, C. (2015). Efficacy of brain gym training on the cognitive performance and fitness level of active older adults: A preliminary study. Journal of Aging and Physical Activity. [CrossRef]
• Chiroma, S. M., Baharuldin, M. T. H., Taib, C. N. M., Amom, Z., Jagadeesan, S., Adenan, M. I., Mahdi, O., & Moklas, M. A. M. (2019). Centella asiatica protects D-galactose/AlCl3 mediated alzheimer’s disease-like rats via PP2A/GSK-3β signaling pathway in their hippocampus. International Journal of Molecular Sciences. [CrossRef]
• Davey, D. A. (2013). Alzheimer’s disease, dementia, mild cognitive impairment and the menopause: A “window of opportunity”? In Women’s Health. [PubMed]
• Dhanasekaran, M., Holcomb, L. A., Hitt, A. R., Tharakan, B., Porter, J. W., Young, K. A., & Manyam, B. V. (2009). Centella asiatica extract selectively decreases amyloid β levels in hippocampus of Alzheimer’s disease animal model. Phytotherapy Research, 23(1), 14–19. [PubMed]
• Fitriana, L. A., Pragholapati, A., Rohaedi, S., Anggadiredja, K., Setiawan, I., & Adnyana, I. K. (2021). Differences of electroencephalography wave with eyes-closed between older women with dementia and without dementia. Journal of Engineering Research. [CrossRef]
• Frederiksen, K. S., Madsen, K., Andersen, B. B., Beyer, N., Garde, E., Høgh, P., Waldemar, G., Hasselbalch, S. G., & Law, I. (2015). O5-04-02: Effect of moderate-high intensity aerobic exercise on beta-amyloid accumulation measured with 11 C-PiB-PET in patients with mild-to-moderate Alzheimer’s disease . Alzheimer’s & Dementia. [CrossRef]
• Head, D., Bugg, J. M., Goate, A. M., Fagan, A. M., Mintun, M. A., Benzinger, T., Holtzman, D. M., & Morris, J. C. (2012). Exercise engagement as a moderator of the effects of APOE genotype on amyloid deposition. Archives of Neurology. [CrossRef]
• Jensen, C. S., Portelius, E., Siersma, V., Høgh, P., Wermuth, L., Blennow, K., et al., (2016). Cerebrospinal fluid amyloid beta and tau concentrations are not modulated by 16 weeks of moderate- to high-intensity physical exercise in patients with Alzheimer disease. Dementia and Geriatric Cognitive Disorders. [Crossref]
• Kang, E.-B., & Cho, J.-Y. (2015). Effect of treadmill exercise on PI3K/AKT/mTOR, autophagy, and Tau hyperphosphorylation in the cerebral cortex of NSE/htau23 transgenic mice. The Journal of Exercise Nutrition and Biochemistry. [Crossref]
• Lee, S. H., Han, J. H., Jin, Y. Y., Lee, I. H., Hong, H. R., & Kang, H. S. (2016). Poor physical fitness is independently associated with mild cognitive impairment in elderly Koreans. Biology of Sport. [Crossref]
• Liang, K. Y., Mintun, M. A., Fagan, A. M., Goate, A. M., Bugg, J. M., Holtzman, D. M., Morris, J. C., & Head, D. (2010). Exercise and Alzheimer’s disease biomarkers in cognitively normal older adults. Annals of Neurology. [Crossref]
• Meyer, C., & O’Keefe, F. (2020). Non-pharmacological interventions for people with dementia: A review of reviews. Dementia, 19(6), 1927–1954. [PubMed]
• Meyer, J. C., Harirari, P., & Schellack, N. (2016). Overview of Alzheimer’s disease and its management. In SA Pharmaceutical Journal.
• Mielke, M. M., Leoutsakos, J. M., Corcoran, C. D., Green, R. C., Norton, M. C., Welsh-Bohmer, K. A., Tschanz, J. T., & Lyketsos, C. G. (2012). Effects of Food and Drug Administration-approved medications for Alzheimer’s disease on clinical progression. Alzheimer’s and Dementia. [CrossRef]
• Nam, E., Lee, Y. B., Moon, C., & Chang, K. A. (2020). Serum tau proteins as potential biomarkers for the assessment of alzheimer’s disease progression. International Journal of Molecular Sciences, 21(14), 1–20. [Crossref]
• Olsson, B., Lautner, R., Andreasson, U., Öhrfelt, A., Portelius, E., Bjerke, M., Hölttä, M., Rosén, C., Olsson, C., Strobel, G., Wu, E., Dakin, K., Petzold, M., Blennow, K., & Zetterberg, H. (2016). CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. The Lancet Neurology. [PubMed]
• Ozbeyli, D., & Cakir, O. K. (2017). The Effects of Different Exercise Modalities in Alzheimer’s Disease. Clinical and Experimental Health Sciences. [CrossRef]
• Prince, M., Ali, G.-C., Guerchet, M., Prina, A. M., Albanese, E., & Wu, Y.-T. (2016). Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimer’s Research & Therapy, 8(1), 23. [Crossref]
• Ramesh, B. N., Indi, S. S., & Rao, K. S. J. (2010). Studies to understand the effect of Centella asiatica on Aβ(42) aggregation in vitro. Current Trends in Biotechnology and Pharmacy.
• Rather, M. A., Thenmozhi, A. J., Manivasagam, T., Bharathi, M. D., Essa, M. M., & Guillemin, G. J. (2018). Neuroprotective role of asiatic acid in aluminium chloride induced rat model of Alzheimer’s disease. Frontiers in Bioscience - Scholar. [Crossref]
• Sari, D. C. R., Arfian, N., Tranggono, U., Setyaningsih, W. A. W., Romi, M. M., & Emoto, N. (2019). Centella asiatica (Gotu kola) ethanol extract up-regulates hippocampal brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling in chronic electrical stress model in rats. Iranian Journal of Basic Medical Sciences. [PubMed]
• Schneider, L. S., Kennedy, R. E., & Cutter, G. R. (2010). Requiring an amyloid-β1-42 biomarker for prodromal Alzheimer’s disease or mild cognitive impairment does not lead to more efficient clinical trials. Alzheimer’s and Dementia. [Crossref]
• Shimizu, Y., Sawada, N., Iwasaki, M., Shikimoto, R., Nozaki, S., Mimura, M., Tsugane, S., & Group, J. P. H. C. P. S. (2019). Reproductive history and risk of cognitive impairment in Japanese women. Maturitas, 12(8), 22–28. [Crossref]
• Soumyanath, A., Zhong, Y. P., Henson, E., Wadsworth, T., Bishop, J., Gold, B. G., & Quinn, J. F. (2012). Centella asiatica extract improves behavioral deficits in a mouse model of Alzheimer’s disease: Investigation of a possible mechanism of action. International Journal of Alzheimer’s Disease, 2012:381974 [Crossref]
• Yu, J.T., Tan, L., & Hardy, J. (2014). Apolipoprotein E in Alzheimer’s Disease: An Update. Annual Review of Neuroscience, 37:79-100 [Crossref]