{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T02:49:56Z","timestamp":1788230996685,"version":"build-2803163510"},"reference-count":85,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"VA merit review","doi-asserted-by":"publisher","award":["O1BX003440"],"award-info":[{"award-number":["O1BX003440"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"VA merit review","doi-asserted-by":"publisher","award":["U19 AT010829"],"award-info":[{"award-number":["U19 AT010829"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"VA merit review","doi-asserted-by":"publisher","award":["U19AT010829-S2"],"award-info":[{"award-number":["U19AT010829-S2"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"VA merit review","doi-asserted-by":"publisher","award":["K08AT012477"],"award-info":[{"award-number":["K08AT012477"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH-NCCIH","award":["O1BX003440"],"award-info":[{"award-number":["O1BX003440"]}]},{"name":"NIH-NCCIH","award":["U19 AT010829"],"award-info":[{"award-number":["U19 AT010829"]}]},{"name":"NIH-NCCIH","award":["U19AT010829-S2"],"award-info":[{"award-number":["U19AT010829-S2"]}]},{"name":"NIH-NCCIH","award":["K08AT012477"],"award-info":[{"award-number":["K08AT012477"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Extracts of the plant Centella asiatica can enhance mitochondrial function, promote antioxidant activity and improve cognitive deficits. Asiatic acid (AA) is one of the constituent triterpene compounds present in the plant. In this study, we explore the effects of AA on brain mitochondrial function, antioxidant response and cognition in a beta-amyloid (A\u03b2)-overexpressing 5xFAD mouse line. Methods: Six- to seven-month-old 5xFAD mice were treated with 1% AA for 4 weeks. In the last week of treatment, associative memory was assessed along with mitochondrial bioenergetics and the expression of mitochondrial and antioxidant response genes from isolated cortical synaptosomes. The A\u03b2 plaque burden was also evaluated. Results: AA treatment resulted in improvements in associative memory in female 5xFAD mice without altering the A\u03b2 plaque burden. Cortical mitochondrial function and mitochondrial gene expression were increased in the AA-treated female 5xFAD mice, as was the expression of antioxidant genes. More modest effects of AA on cortical mitochondrial function and mitochondrial and antioxidant gene expression were observed in male 5xFAD mice. Conclusions: Oral AA treatment improved cognitive and mitochondrial function and activated antioxidant in A\u03b2-overexpressing mice. These changes occurred independent of alterations in A\u03b2 plaque burden, suggesting that AA could have translational therapeutic relevance in later-stage AD when plaques are well established.<\/jats:p>","DOI":"10.3390\/nu17040729","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T05:34:26Z","timestamp":1739943266000},"page":"729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Oral Asiatic Acid Improves Cognitive Function and Modulates Antioxidant and Mitochondrial Pathways in Female 5xFAD Mice"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0784-5442","authenticated-orcid":false,"given":"Samantha","family":"Varada","sequence":"first","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Chamberlin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillie","family":"Bui","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikah S.","family":"Brandes","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Gladen-Kolarsky","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wyatt","family":"Hack","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody J.","family":"Neff","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara H.","family":"Brumbach","sequence":"additional","affiliation":[{"name":"OHSU-PSU School of Public Health, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1569-6453","authenticated-orcid":false,"given":"Amala","family":"Soumyanath","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7305-2256","authenticated-orcid":false,"given":"Joseph F.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"},{"name":"Department of Neurology and Parkinson\u2019s Disease Research Education and Clinical Care Center (PADRECC), VA Portland Healthcare System, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora E.","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"ref_1","unstructured":"Alzheimer\u2019s Association (2023). 2023 Alzheimer\u2019s Disease Facts and Figures, Alzheimer\u2019s & Dementia, Alzheimer\u2019s Association."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9758\/cpn.2017.15.1.1","article-title":"Mechanisms of Alzheimer\u2019s Disease Pathogenesis and Prevention: The Brain, Neural Pathology, N-methyl-D-aspartate Receptors, Tau Protein and Other Risk Factors","volume":"15","author":"Kocahan","year":"2017","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Agarwal, M., Alam, M.R., Haider, M.K., Malik, M.Z., and Kim, D.K. (2020). Alzheimer\u2019s Disease: An Overview of Major Hypotheses and Therapeutic Options in Nanotechnology. Nanomaterials, 11.","DOI":"10.3390\/nano11010059"},{"key":"ref_4","first-page":"3","article-title":"Oxidative stress mediates the pathogenic effect of different Alzheimer\u2019s disease risk factors","volume":"2","author":"Guglielmotto","year":"2010","journal-title":"Front. Aging Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1111\/j.1471-4159.2006.03907.x","article-title":"Oxidative stress and neurodegeneration: Where are we now?","volume":"97","author":"Halliwell","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Suzen, S., Tucci, P., Profumo, E., Buttari, B., and Saso, L. (2022). A Pivotal Role of Nrf2 in Neurodegenerative Disorders: A New Way for Therapeutic Strategies. Pharmaceuticals, 15.","DOI":"10.3390\/ph15060692"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"675","DOI":"10.2174\/1570159X19666210517114016","article-title":"Mitochondrial Dysfunction in Alzheimer\u2019s Disease: Opportunities for Drug Development","volume":"20","author":"Bhatia","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.neurobiolaging.2016.12.029","article-title":"Mitochondrial genes are altered in blood early in Alzheimer\u2019s disease","volume":"53","author":"Lunnon","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12516","DOI":"10.1073\/pnas.1819541116","article-title":"NRF2\/ARE pathway negatively regulates BACE1 expression and ameliorates cognitive deficits in mouse Alzheimer\u2019s models","volume":"116","author":"Bahn","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mcn.2018.09.002","article-title":"Centella asiatica attenuates hippocampal mitochondrial dysfunction and improves memory and executive function in beta-amyloid overexpressing mice","volume":"93","author":"Gray","year":"2018","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.3233\/JAD-210271","article-title":"Prolonged Treatment with Centella asiatica Improves Memory, Reduces Amyloid-beta Pathology, and Activates NRF2-Regulated Antioxidant Response Pathway in 5xFAD Mice","volume":"81","author":"Zweig","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cotox.2016.10.002","article-title":"The multifaceted role of Nrf2 in mitochondrial function","volume":"1","author":"Kostov","year":"2016","journal-title":"Curr. Opin. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4925","DOI":"10.1007\/s12035-018-1420-2","article-title":"Nootropic and Anti-Alzheimer\u2019s Actions of Medicinal Plants: Molecular Insight into Therapeutic Potential to Alleviate Alzheimer\u2019s Neuropathology","volume":"56","author":"Uddin","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2174\/187221411794351833","article-title":"Exploring the Role of \u201cBrahmi\u201d (Bacopa monnieri and Centella asiatica) in Brain Function and Therapy","volume":"5","author":"Shinomol","year":"2011","journal-title":"Recent Pat. Endocr. Metab. Immune Drug Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11101-017-9528-y","article-title":"Centella asiatica\u2014Phytochemistry and mechanisms of neuroprotection and cognitive enhancement","volume":"17","author":"Gray","year":"2018","journal-title":"Phytochem. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jep.2016.01.013","article-title":"Centella asiatica modulates antioxidant and mitochondrial pathways and improves cognitive function in mice","volume":"180","author":"Gray","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"933","DOI":"10.3233\/JAD-142217","article-title":"Centella asiatica Attenuates Amyloid-beta-Induced Oxidative Stress and Mitochondrial Dysfunction","volume":"45","author":"Gray","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e01024","DOI":"10.1002\/brb3.1024","article-title":"Centella asiatica increases hippocampal synaptic density and improves memory and executive function in aged mice","volume":"8","author":"Gray","year":"2018","journal-title":"Brain Behav."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7023091","DOI":"10.1155\/2017\/7023091","article-title":"Centella asiatica Attenuates Mitochondrial Dysfunction and Oxidative Stress in Abeta-Exposed Hippocampal Neurons","volume":"2017","author":"Gray","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Matthews, D.G., Caruso, M., Murchison, C.F., Zhu, J.Y., Wright, K.M., Harris, C.J., Gray, N.E., Quinn, J.F., and Soumyanath, A. (2019). Centella asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice. Antioxidants, 8.","DOI":"10.3390\/antiox8120630"},{"key":"ref_22","first-page":"381974","article-title":"Centella asiatica Extract Improves Behavioral Deficits in a Mouse Model of Alzheimer\u2019s Disease: Investigation of a Possible Mechanism of Action","volume":"2012","author":"Soumyanath","year":"2012","journal-title":"Int. J. Alzheimers Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3595","DOI":"10.2147\/DDDT.S179876","article-title":"Asiatic acid ameliorates CCl(4)-induced liver fibrosis in rats: Involvement of Nrf2\/ARE, NF-kappaB\/IkappaBalpha, and JAK1\/STAT3 signaling pathways","volume":"12","author":"Fan","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8128","DOI":"10.1021\/acs.jafc.7b01590","article-title":"Asiaticoside Mitigates the Allergic Inflammation by Abrogating the Degranulation of Mast Cells","volume":"65","author":"Jiang","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"134386","DOI":"10.1016\/j.neulet.2019.134386","article-title":"Madecassoside ameliorates lipopolysaccharide-induced neurotoxicity in rats by activating the Nrf2-HO-1 pathway","volume":"709","author":"Liu","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105712","DOI":"10.1016\/j.intimp.2019.105712","article-title":"Asiatic acid inhibits cardiac fibrosis throughNrf2\/HO-1 and TGF-beta1\/Smads signaling pathways in spontaneous hypertension rats","volume":"74","author":"Meng","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.biopha.2016.10.015","article-title":"Madecassic Acid protects against hypoxia-induced oxidative stress in retinal microvascular endothelial cells via ROS-mediated endoplasmic reticulum stress","volume":"84","author":"Yang","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3233\/JAD-131913","article-title":"Caffeoylquinic acids in Centella asiatica protect against amyloid-beta toxicity","volume":"40","author":"Gray","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1111\/jcmm.17635","article-title":"Therapeutic properties and pharmacological activities of asiaticoside and madecassoside: A review","volume":"27","author":"Bandopadhyay","year":"2023","journal-title":"J. Cell. Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Tan, S.C., Bhattamisra, S.K., Chellappan, D.K., and Candasamy, M. (2021). Actions and Therapeutic Potential of Madecassoside and Other Major Constituents of Centella asiatica: A Review. Appl. Sci., 11.","DOI":"10.3390\/app11188475"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wong, J.H., Barron, A.M., and Abdullah, J.M. (2021). Mitoprotective Effects of Centella asiatica (L.) Urb.: Anti-Inflammatory and Neuroprotective Opportunities in Neurodegenerative Disease. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.687935"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"413","DOI":"10.3892\/etm.2016.4004","article-title":"Asiaticoside ameliorates beta-amyloid-induced learning and memory deficits in rats by inhibiting mitochondrial apoptosis and reducing inflammatory factors","volume":"13","author":"Zhang","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Matthews, D.G., Caruso, M., Alcazar Magana, A., Wright, K.M., Maier, C.S., Stevens, J.F., Gray, N.E., Quinn, J.F., and Soumyanath, A. (2020). Caffeoylquinic Acids in Centella asiatica Reverse Cognitive Deficits in Male 5XFAD Alzheimer\u2019s Disease Model Mice. Nutrients, 12.","DOI":"10.3390\/nu12113488"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e15853","DOI":"10.1016\/j.heliyon.2023.e15853","article-title":"Neuroprotective mechanisms of Asiatic acid","volume":"9","author":"Ding","year":"2023","journal-title":"Heliyon"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"287","DOI":"10.2741\/e823","article-title":"Asiatic acid nullified aluminium toxicity in in vitro model of Alzheimer\u2019s disease","volume":"10","author":"Manivasagam","year":"2018","journal-title":"Front. Biosci. Elite"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"442","DOI":"10.4062\/biomolther.2018.188","article-title":"Asiatic Acid Protects Dopaminergic Neurons from Neuroinflammation by Suppressing Mitochondrial Ros Production","volume":"27","author":"Chen","year":"2019","journal-title":"Biomol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1080\/1028415X.2015.1135559","article-title":"Neuroprotective effect of asiatic acid on rotenone-induced mitochondrial dysfunction and oxidative stress-mediated apoptosis in differentiated SH-SYS5Y cells","volume":"20","author":"Nataraj","year":"2017","journal-title":"Nutr. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1007\/s11064-008-9844-0","article-title":"Protective effects of asiatic acid on rotenone- or H2O2-induced injury in SH-SY5Y cells","volume":"34","author":"Xiong","year":"2009","journal-title":"Neurochem. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chaisawang, P., Sirichoat, A., Chaijaroonkhanarak, W., Pannangrong, W., Sripanidkulchai, B., Wigmore, P., and Welbat, J.U. (2017). Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy. PLoS ONE., 12.","DOI":"10.1371\/journal.pone.0180650"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s11011-017-0143-9","article-title":"Asiatic acid prevents the quinolinic acid-induced oxidative stress and cognitive impairment","volume":"33","author":"Loganathan","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.taap.2017.11.023","article-title":"Asiatic acid ameliorates hepatic ischemia\/reperfusion injury in rats via mitochondria-targeted protective mechanism","volume":"338","author":"Lu","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lv, H., Qi, Z., Wang, S., Feng, H., Deng, X., and Ci, X. (2017). Asiatic Acid Exhibits Anti-inflammatory and Antioxidant Activities against Lipopolysaccharide and d-Galactosamine-Induced Fulminant Hepatic Failure. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00785"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jep.2010.12.010","article-title":"Effects of asiatic acid on passive and active avoidance task in male Spraque-Dawley rats","volume":"134","author":"Nasir","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1007\/s11064-017-2183-2","article-title":"Neurotrophic Effect of Asiatic acid, a Triterpene of Centella asiatica Against Chronic 1-Methyl 4-Phenyl 1, 2, 3, 6-Tetrahydropyridine Hydrochloride\/Probenecid Mouse Model of Parkinson\u2019s disease: The Role of MAPK, PI3K-Akt-GSK3beta and mTOR Signalling Pathways","volume":"42","author":"Nataraj","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1186\/s12974-017-1009-0","article-title":"Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB\/STAT3\/ERK and mitochondria-mediated apoptosis pathway","volume":"14","author":"Park","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Welbat, J.U., Sirichoat, A., Chaijaroonkhanarak, W., Prachaney, P., Pannangrong, W., Pakdeechote, P., Sripanidkulchai, B., and Wigmore, P. (2016). Asiatic Acid Prevents the Deleterious Effects of Valproic Acid on Cognition and Hippocampal Cell Proliferation and Survival. Nutrients, 8.","DOI":"10.3390\/nu8050303"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Welbat, J.U., Chaisawang, P., Pannangrong, W., and Wigmore, P. (2018). Neuroprotective Properties of Asiatic Acid against 5-Fluorouracil Chemotherapy in the Hippocampus in an Adult Rat Model. Nutrients, 10.","DOI":"10.3390\/nu10081053"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/aps.2012.3","article-title":"Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells","volume":"33","author":"Xu","year":"2012","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1211\/0022357044391","article-title":"Asiatic acid derivatives enhance cognitive performance partly by improving acetylcholine synthesis","volume":"56","author":"Kim","year":"2004","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lu, C.W., Lin, T.Y., Pan, T.L., Wang, P.W., Chiu, K.M., Lee, M.Y., and Wang, S.J. (2021). Asiatic Acid Prevents Cognitive Deficits by Inhibiting Calpain Activation and Preserving Synaptic and Mitochondrial Function in Rats with Kainic Acid-Induced Seizure. Biomedicines, 9.","DOI":"10.3390\/biomedicines9030284"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.intimp.2019.04.028","article-title":"Neuroprotective effects of isoliquiritigenin against cognitive impairment via suppression of synaptic dysfunction, neuronal injury, and neuroinflammation in rats with kainic acid-induced seizures","volume":"72","author":"Zhu","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/pca.2936","article-title":"Integration of mass spectral fingerprinting analysis with precursor ion (MS1) quantification for the characterisation of botanical extracts: Application to extracts of Centella asiatica (L.) Urban","volume":"31","author":"Wright","year":"2020","journal-title":"Phytochem Anal."},{"key":"ref_53","first-page":"1379","article-title":"The metabolism of asiatic acid,-madecassic acid and asiaticoside in the rat","volume":"21","author":"Chassaud","year":"1971","journal-title":"Arzneimittelforschung"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.3390\/molecules16021310","article-title":"Triterpene composition and bioactivities of Centella asiatica","volume":"16","author":"Hashim","year":"2011","journal-title":"Molecules"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.jcis.2008.05.046","article-title":"Association (micellization) and partitioning of aglycon triterpenoids","volume":"325","author":"Rafat","year":"2008","journal-title":"J. Colloid Interface Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/BF03190180","article-title":"The comparative steady-state bioavailability of the active ingredients of Madecassol","volume":"18","author":"Rush","year":"1993","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1080\/00498254.2016.1273562","article-title":"Comparative pharmacokinetics between madecassoside and asiaticoside presented in a standardised extract of Centella asiatica, ECa 233 and their respective pure compound given separately in rats","volume":"48","author":"Hengjumrut","year":"2018","journal-title":"Xenobiotica"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1177\/000331970105202S10","article-title":"Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: A clinical prospective randomized trial with a microcirculatory model","volume":"52","author":"Cesarone","year":"2001","journal-title":"Angiology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0378-8741(90)90033-P","article-title":"Pharmacokinetics of the total triterpenic fraction of Centella Asiatica after Single and Multiple Administrations to Healthy Volunteers, A New Assay for Asiatic Acid","volume":"28","author":"Grimaldi","year":"1990","journal-title":"J. Ethnopharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1177\/000331970105202S12","article-title":"Total triterpenic fraction of Centella asiatica in the treatment of venous hypertension: A clinical, prospective, randomized trial using a combined microcirculatory model","volume":"52","author":"Incandela","year":"2001","journal-title":"Angiology"},{"key":"ref_61","first-page":"12","article-title":"Centella asiatica triterpenes for diabetic neuropathy: A randomized, double-blind, placebo-controlled, pilot clinical study","volume":"20","author":"Lou","year":"2018","journal-title":"Esper Dermatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","article-title":"Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer\u2019s disease mutations: Potential factors in amyloid plaque formation","volume":"26","author":"Oakley","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Gray, N.E., Hack, W., Brandes, M.S., Zweig, J.A., Yang, L., Marney, L., Choi, J., Magana, A.A., Cerruti, N., and McFerrin, J. (2024). Amelioration of age-related cognitive decline and anxiety in mice by Centella asiatica extract varies by sex, dose and mode of administration. Front. Aging, 5.","DOI":"10.3389\/fragi.2024.1357922"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bandc.2012.10.005","article-title":"A model of amygdala-hippocampal-prefrontal interaction in fear conditioning and extinction in animals","volume":"81","author":"Moustafa","year":"2013","journal-title":"Brain Cogn."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1002\/rcm.1155","article-title":"Quantitative analysis of betulinic acid in mouse, rat and dog plasma using electrospray liquid chromatography\/mass spectrometry","volume":"17","author":"Cheng","year":"2003","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1002\/rcm.6291","article-title":"A liquid chromatography\/electrospray ionization tandem mass spectrometric method for quantification of asiatic acid from plasma: Application to pharmacokinetic study in rats","volume":"26","author":"Nair","year":"2012","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"512","DOI":"10.30574\/wjarr.2022.15.1.0726","article-title":"Centella asiatica: A traditional herbal medicine","volume":"15","author":"Krupa","year":"2022","journal-title":"World J. Adv. Res. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Saha, S., Buttari, B., Profumo, E., Tucci, P., and Saso, L. (2021). A Perspective on Nrf2 Signaling Pathway for Neuroinflammation: A Potential Therapeutic Target in Alzheimer\u2019s and Parkinson\u2019s Diseases. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.787258"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.biopha.2017.01.067","article-title":"Asiatic acid enhances Nrf2 signaling to protect HepG2 cells from oxidative damage through Akt and ERK activation","volume":"88","author":"Qi","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s12012-017-9424-0","article-title":"Asiatic Acid Ameliorates Doxorubicin-Induced Cardiac and Hepato-Renal Toxicities with Nrf2 Transcriptional Factor Activation in Rats","volume":"18","author":"Kamble","year":"2018","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.lfs.2016.05.004","article-title":"Neuroprotective effect of asiatic acid against spinal cord injury in rats","volume":"157","author":"Jiang","year":"2016","journal-title":"Life Sci."},{"key":"ref_72","first-page":"360","article-title":"Asiatic acid attenuates traumatic brain injury via upregulating Nrf2 and HO-1 expression","volume":"11","author":"Han","year":"2018","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1211\/jpp.58.2.0010","article-title":"Mechanism underlying mitochondrial protection of asiatic acid against hepatotoxicity in mice","volume":"58","author":"Gao","year":"2006","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Nagoor Meeran, M.F., Goyal, S.N., Suchal, K., Sharma, C., Patil, C.R., and Ojha, S.K. (2018). Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00892"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1002\/jnr.22071","article-title":"Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia","volume":"87","author":"Krishnamurthy","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neurobiolaging.2020.11.019","article-title":"Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging","volume":"100","author":"Zweig","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neures.2019.05.001","article-title":"Coffee polyphenols prevent cognitive dysfunction and suppress amyloid beta plaques in APP\/PS2 transgenic mouse","volume":"154","author":"Ishida","year":"2020","journal-title":"Neurosci. Res."},{"key":"ref_78","first-page":"115","article-title":"Cognitive-Enhancing Effects of a Polyphenols-Rich Extract from Fruits without Changes in Neuropathology in an Animal Model of Alzheimer\u2019s Disease","volume":"55","author":"Dudonne","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1017\/S0007114509992364","article-title":"Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment","volume":"103","author":"Krikorian","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5736","DOI":"10.1021\/jf300277g","article-title":"Concord grape juice supplementation and neurocognitive function in human aging","volume":"60","author":"Krikorian","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Krikorian, R., Skelton, M.R., Summer, S.S., Shidler, M.D., and Sullivan, P.G. (2022). Blueberry Supplementation in Midlife for Dementia Risk Reduction. Nutrients, 14.","DOI":"10.3390\/nu14081619"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.neurol.2019.08.005","article-title":"Mediterranean diet: The role of long-chain omega-3 fatty acids in fish; polyphenols in fruits, vegetables, cereals, coffee, tea, cacao and wine; probiotics and vitamins in prevention of stroke, age-related cognitive decline, and Alzheimer disease","volume":"175","author":"Roman","year":"2019","journal-title":"Rev. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Javonillo, D.I., Tran, K.M., Phan, J., Hingco, E., Kram\u00e1r, E.A., da Cunha, C., Forner, S., Kawauchi, S., Milinkevicuite, G., and Gomez-Arboledas, A. (2021). Systematic Phenotyping and Characterization of the 3xTg-AD Mouse Model of Alzheimer\u2019s Disease. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.785276"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"755","DOI":"10.3233\/JAD-210523","article-title":"Sex Differences in Behavior and Molecular Pathology in the 5XFAD Model","volume":"85","author":"Sil","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1007\/s11427-020-1810-y","article-title":"Critical thinking on amyloid-beta-targeted therapy: Challenges and perspectives","volume":"64","author":"Sun","year":"2021","journal-title":"Sci. China Life Sci."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/4\/729\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:37:34Z","timestamp":1760027854000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/4\/729"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":85,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["nu17040729"],"URL":"https:\/\/doi.org\/10.3390\/nu17040729","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]}}}