Extracellular vesicle-based drug delivery system boosts phytochemicals’ therapeutic effect for neurodegenerative diseases
Zhenzhu Zhu, Liuyue Liao, Hongzhi Qiao
Extracellular vesicle-based drug delivery system boosts phytochemicals’ therapeutic effect for neurodegenerative diseases
Neurodegenerative diseases (NDs) are a major threat to the elderly, and efficient therapy is rarely available. A group of phytochemicals has been shown to ameliorate NDs; however, poor stability, low bioavailability, and reduced drug accumulation in brain tissue limit their application in NDs. Therefore, a targeted drug delivery system is a feasible treatment strategy for NDs. Extracellular vesicles (EVs) possess many favorable bioactivities and are excellent carriers for targeting brain tissue. This review summarizes EVs as novel phytochemical carriers in ND therapy. First, we discuss the current challenges of ND therapy and the therapeutic effects of phytochemicals for NDs. Second, we highlight the ability of EVs to cross the blood-brain barrier and act as drug carriers to enhance the therapeutic efficacy of drugs for NDs. Finally, encapsulation strategies for phytochemicals in EVs are particularly reviewed, as they are critical for obtaining high loading efficacy and stable drug delivery systems. This review provides new insights into EV-based drug delivery systems for improving the therapeutic effect of phytochemicals for ND treatment. Therefore, the release rate and pharmacokinetics of phytochemicals should be well controlled to ensure the therapeutic efficacy of phytochemical-loaded EVs in the brain.
Bioavailability / Brain-targeting / Extracellular vesicle-based drug delivery system / Neurodegenerative diseases / Phytochemicals
[[1]] |
Alzheimer’s Association.Alzheimer’s disease facts and figures. Alzheimers Dement. 2022;18(4):700-789.
|
[[2]] |
Webber CJ, Lei SE, Wolozin B.The pathophysiology of neurodegenerative disease: disturbing the balance between phase separation and irreversible aggregation. Prog Mol Biol Transl Sci. 2020;174:187-223.
|
[[3]] |
Kiaei M.New hopes and challenges for treatment of neurodegenerative disorders: great opportunities for young neuroscientists. Basic Clin Neurosci. 2013;4(1):3-4.
|
[[4]] |
Durães F, Pinto M, Sousa E. Old drugs as new treatments for neurodegenerative diseases. Pharmaceuticals (Basel). 2018;11(2):44.
|
[[5]] |
Gupta J, Sharma S, Sharma NR, et al.Phytochemicals enriched in spices: a source of natural epigenetic therapy. Arch Pharm Res. 2020;43(2):171-186.
|
[[6]] |
Rodriguez-Casado A.The health potential of fruits and vegetables phytochemicals: notable examples. Crit Rev Food Sci Nutr. 2016;56(7):1097-1107.
|
[[7]] |
Venkatesan R, Ji E, Kim SY.Phytochemicals that regulate neurodegenerative disease by targeting neurotrophins: a comprehensive review. Biomed Res Int. 2015;2015:814068.
|
[[8]] |
Heiss CN, Olofsson LE.The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system. [J] Neuroendocrinol. 2019;31(5):e12684.
|
[[9]] |
Yadav DK.Potential therapeutic strategies of phytochemicals in neurodegenerative disorders. Curr Top Med Chem. 2021;21(31):2814-2838.
|
[[10]] |
Muhammad SA.Are extracellular vesicles new hope in clinical drug delivery for neurological disorders? Neurochem Int. 2021;144:104955.
|
[[11]] |
Fan L, Mao C, Hu X, et al.New insights into the pathogenesis of Alzheimer’s disease. Front Neurol. 2020;10:1312.
|
[[12]] |
Hirsch EC, Jenner P, Przedborski S.Pathogenesis of Parkinson’s disease. Mov Disord. 2013;28(1):24-30.
|
[[13]] |
Jimenez-Sanchez M, Licitra F, Underwood BR, et al. Huntington’s disease: mechanisms of pathogenesis and therapeutic strategies. Cold Spring Harb Perspect Med. 2017;7(7):a024240.
|
[[14]] |
Saberi S, Stauffer JE, Schulte DJ, et al. Neuropathology of amyotrophic lateral sclerosis and its variants. Neurol Clin. 2015;33(4):855-876.
|
[[15]] |
Lee JH, Yang DS, Goulbourne CN, et al. Faulty autolysosome acidification in Alzheimer’s disease mouse models induces autophagic build-up of Aβ in neurons, yielding senile plaques. Nat Neurosci. 2022;25(6):688-701.
|
[[16]] |
Abbott NJ, Patabendige AA, Dolman DE, et al.Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13-25.
|
[[17]] |
Löscher W, Potschka H.Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx. 2005;2(1):86-98.
|
[[18]] |
Pardridge WM.Drug transport across the blood-brain barrier. [J] Cereb Blood Flow Metab. 2012;32(11):1959-1972.
|
[[19]] |
Reynolds JL, Mahato RI.Nanomedicines for the treatment of CNS diseases. [J] Neuroimmune Pharmacol. 2017;12(1):1-5.
|
[[20]] |
Briggs R, Kennelly SP, O’Neill D. Drug treatments in Alzheimer’s disease. Clin Med (Lond). 2016;16(3):247-253.
|
[[21]] |
Khoury R, Patel K, Gold J, et al.Recent progress in the pharmacotherapy of Alzheimer’s disease. Drugs Aging. 2017;34(11):811-820.
|
[[22]] |
Das B, Yan R.Role of BACE1 in Alzheimer’s synaptic function. Trans Nurodegener. 2017;6(1):23.
|
[[23]] |
Wang X, Sun G, Feng T, et al.Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression. Cell Res. 2019;29(10):787-803.
|
[[24]] |
Cummings J, Aisen P, Apostolova LG, et al.Aducanumab: appropriate use recommendations. [J] Prev Alzheimers Dis. 2021;8(4):398-410.
|
[[25]] |
Selkoe DJ.Treatments for Alzheimer’s disease emerging. Science. 2021;373(6555):624-626.
|
[[26]] |
Koo EH.Preclinical and clinical understanding: major gaps in our understanding and capabilities. Translational Neuroscience: Toward New Therapies.Cambridge, MA: MIT Press2015.
|
[[27]] |
Patra S, Nayak R, Patro S, et al.Chemical diversity of dietary phytochemicals and their mode of chemoprevention. Biotechnol Rep (Amst). 2021;30:e00633.
|
[[28]] |
Velmurugan BK, Rathinasamy B, Lohanathan BP, et al.Neuroprotective role of phytochemicals. Molecules. 2018; 23(10):2485.
|
[[29]] |
Yu W, Tao M, Zhao Y, et al.4’-Methoxyresveratrol alleviated AGE-induced inflammation via RAGE-mediated NF-κB and NLRP3 inflammasome pathway. Molecules. 2018;23(6):1447.
|
[[30]] |
Ladiwala AR, Lin JC, Bale SS, et al.Resveratrol selectively remodels soluble oligomers and fibrils of amyloid Abeta into off-pathway conformers. [J] Biol Chem. 2010;285(31):24228-24237.
|
[[31]] |
Karuppagounder SS, Pinto JT, Xu H, et al.Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer’s disease. Neurochem Int. 2009;54(2):111-118.
|
[[32]] |
Zhang L, Fang Y, Cheng X, et al. Curcumin exerts effects on the pathophysiology of Alzheimer’s disease by regulating PI(3,5)P2 and transient receptor potential mucolipin-1 expression. Front Neurol. 2017;8:531.
|
[[33]] |
Xia XJ, Lian YG, Zhao HY, et al.Curcumin protects from oxidative stress and inhibits α-synuclein aggregation in MPTP induced Parkinsonian mice. Int [J] Clin Exp Med. 2016;9:2654-2665.
|
[[34]] |
Jiang TF, Zhang YJ, Zhou HY, et al.Curcumin ameliorates the neurodegenerative pathology in A53T α-synuclein cell model of Parkinson’s disease through the downregulation of mTOR/p70S6K signaling and the recovery of macroautophagy. [J] Neuroimmune Pharmacol. 2013;8:356-369.
|
[[35]] |
Sharma N, Nehru B. Curcumin affords neuroprotection and inhibits α-synuclein aggregation in lipopolysaccharide-induced Parkinson’s disease model. Inflammopharmacology. 2018;26(2):349-360.
|
[[36]] |
Liu Y, Zhou H, Yin T, et al.Quercetin-modified gold-palladium nanoparticles as a potential autophagy inducer for the treatment of Alzheimer’s disease. [J] Colloid Interface Sci. 2019;552:388-400.
|
[[37]] |
Regitz C, Dußling LM, Wenzel U. Amyloid-beta (Aβ1-42)-induced paralysis in Caenorhabditis elegans is inhibited by the polyphenol quercetin through activation of protein degradation pathways. Mol Nutr Food Res. 2014;58(10):1931-1940.
|
[[38]] |
Zhu M, Han S, Fink AL.Oxidized quercetin inhibits α-synuclein fibrillization. Biochim Biophys Acta. 2013;1830(4):2872-2881.
|
[[39]] |
El-Horany HE, El-Latif RN,ElBatsh MM, et al. Ameliorative effect of quercetin on neurochemical and behavioral deficits in rotenone rat model of Parkinson’s Disease: modulating autophagy (quercetin on experimental Parkinson’s Disease). J Biochem Mol Toxicol. 2016;30:360-369.
|
[[40]] |
Pogacnik L, Pirc K, Palmela I, et al.Potential for brain accessibility and analysis of stability of selected flavonoids in relation to neuroprotection in vitro. Brain Res. 2016;1651:17-26.
|
[[41]] |
Winter AN, Ross EK, Khatter S, et al.Chemical basis for the disparate neuroprotective effects of the anthocyanins, callistephin and kuromanin, against nitrosative stress. Free Rad Bio Med. 2017;103:23-34.
|
[[42]] |
Rehman SU, Shah SA, Ali T, et al.Anthocyanins reversed D-galactose-induced oxidative stress and neuroinflammation mediated cognitive impairment in adult rats. Mol Neurobio. 2017;54:255-271.
|
[[43]] |
Chen Y, Chen J, Sun X, et al.Evaluation of the neuroprotective effect of EGCG: a potential mechanism of mitochondrial dysfunction and mitochondrial dynamics after subarachnoid hemorrhage. Food Funct. 2018;9:6349-6359.
|
[[44]] |
Šneideris T, Baranauskienė L, Cannon JG, et al.Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives. PeerJ. 2015;3:e1271.
|
[[45]] |
Xu Y, Xie M, Xue J, et al. EGCG ameliorates neuronal and behavioral defects by remodeling gut microbiota and TotM expression in Drosophila models of Parkinson’s disease. FASEB J. 2020;34(4):5931-5950.
|
[[46]] |
Abdallah IM, Al-Shami KM, Yang E, et al.Oleuropein-rich olive leaf extract attenuates neuroinflammation in the Alzheimer’s disease mouse model. ACS Chem Neurosci. 2022;13(7):1002-1013.
|
[[47]] |
Filomeni G, Graziani I, De Zio D, et al. Neuroprotection of kaempferol by autophagy in models of rotenone-mediated acute toxicity: possible implications for Parkinson’s disease. Neurobiol Aging. 2012;33(4):767-785.
|
[[48]] |
Han X, Sun S, Sun Y, et al. Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: implications for Parkinson disease. Autophagy. 2019;15(11):1860-1881.
|
[[49]] |
Chen Y, Chen Y, Liang Y, et al. Berberine mitigates cognitive decline in an Alzheimer’s disease mouse model by targeting both tau hyperphosphorylation and autophagic clearance. Biomed Pharmacother. 2020;121:109670.
|
[[50]] |
Huang M, Jiang X, Liang Y, et al.Berberine improves cognitive impairment by promoting autophagic clearance and inhibiting production of β-amyloid in APP/tau/PS1 mouse model of Alzheimer’s disease. Exp Gerontol. 2017;91:25-33.
|
[[51]] |
Jiang W, Wei W, Gaertig MA, et al.Therapeutic effect of berberine on Huntington’s Disease transgenic mouse model. PLoS One. 2015;10:e0134142.
|
[[52]] |
Chang CF, Lee YC, Lee KH, et al.Therapeutic effect of berberine on TDP-43-related pathogenesis in FTLD and ALS. [J] Biomed Sci. 2016;23(1):72.
|
[[53]] |
Kakkar V, Kaur IP.Evaluating potential of curcumin loaded solid lipid nanoparticles in aluminium induced behavioural, biochemical and histopathological alterations in mice brain. Food Chem Toxicol. 2011;49(11):2906-2913.
|
[[54]] |
Liu M, Chen F, Sha L, et al.(-)-Epigallocatechin-3-gallate ameliorates learning and memory deficits by adjusting the balance of TrkA/p75NTR signaling in APP/PS1 transgenic mice. Mol Neurobiol. 2014;49(3):1350-1363.
|
[[55]] |
Liu F, Zhao F, Wang W, et al.Cyanidin-3-O-glucoside inhibits Aβ40 fibrillogenesis, disintegrates preformed fibrils, and reduces amyloid cytotoxicity. Food Funct. 2020;11(3):2573-2587.
|
[[56]] |
Bai D, Jin G, Zhang D, et al.Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice. [J] Physiol Sci. 2019;69(4):643-652.
|
[[57]] |
Inden M, Takagi A, Kitai H, et al.Kaempferol has potent protective and antifibrillogenic effects for α-synuclein neurotoxicity in vitro. Int [J] Mol Sci. 2021;22(21):11484.
|
[[58]] |
Jiang W, Wei W, Gaertig MA, et al.Therapeutic effect of berberine on Huntington’s disease transgenic mouse model. PLoS One. 2015;10(7):e0134142.
|
[[59]] |
Tang S.Advance on the nano delivery system of curcumin. E3S Web Conf. 2020;185(3):04068.
|
[[60]] |
Schnatz A, Müller C, Brahmer A, et al.Extracellular vesicles in neural cell interaction and CNS homeostasis. FASEB Bioadv. 2021;3(8):577-592.
|
[[61]] |
Properzi F, Ferroni E, Poleggi A, et al.The regulation of exosome function in the CNS: implications for neurodegeneration. Swiss Med Wkly. 2015;145:w14204.
|
[[62]] |
Zaborowski MP, Balaj L, Breakefield XO, et al.Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience. 2015;65(8):783-797.
|
[[63]] |
Kalluri R, LeBleu VS. The biology, function,biomedical applications of exosomes. Science. 2020;367(6478):eaau6977.
|
[[64]] |
Dad HA, Gu TW, Zhu AQ, et al.Plant exosome-like nanovesicles: emerging therapeutics and drug delivery nanoplatforms. Mol Ther. 2021;29(1):13-31.
|
[[65]] |
Skotland T, Sagini K, Sandvig K, et al.An emerging focus on lipids in extracellular vesicles. Adv Drug Deliv Rev. 2020;159:308-321.
|
[[66]] |
Hu Q, Su H, Li J, et al.Clinical applications of exosome membrane proteins. Precis Clin Med. 2020;3(1):54-66.
|
[[67]] |
Gusachenko ON, Zenkova MA, Vlassov VV.Nucleic acids in exosomes: disease markers and intercellular communication molecules. Biochemistry (Mosc). 2013;78(1):1-7.
|
[[68]] |
Théry C.Exosomes: secreted vesicles and intercellular communications. F1000 Biol Rep. 2011;3:15.
|
[[69]] |
Doyle LM, Wang MZ.Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells. 2019;8(7):727.
|
[[70]] |
Chen YA, Lu CH, Ke CC, et al.Mesenchymal stem cell-derived extracellular vesicle-based therapy for Alzheimer’s disease: progress and opportunity. Membranes (Basel). 2021;11(10):796.
|
[[71]] |
Upadhya R, Zingg W, Shetty S, et al. Astrocyte-derived extracellular vesicles: Neuroreparative properties and role in the pathogenesis of neurodegenerative disorders. [J] Control Release. 2020;323:225-239.
|
[[72]] |
Casella G, Rasouli J, Boehm A, et al. Oligodendrocyte-derived extracellular vesicles as antigen-specific therapy for autoimmune neuroinflammation in mice. Sci Transl Med.2020;12(568):eaba0599.
|
[[73]] |
Gabrielli M, Prada I, Joshi P, et al.Microglial large extracellular vesicles propagate early synaptic dysfunction in Alzheimer’s disease. Brain. 2022;145(8):2849-2868.
|
[[74]] |
Croese T, Furlan R.Extracellular vesicles in neurodegenerative diseases. Mol Aspects Med. 2018;60:52-61.
|
[[75]] |
Rastogi S, Sharma V, Bharti PS, et al.The evolving landscape of exosomes in neurodegenerative diseases: exosomes characteristics and a promising role in early diagnosis. Int [J] Mol Sci. 2021;22(1):440.
|
[[76]] |
Zhong J, Xia B, Shan S, et al.High-quality milk exosomes as oral drug delivery system. Biomaterials. 2021;277:121126.
|
[[77]] |
Warren MR, Zhang C, Vedadghavami A, et al.Milk exosomes with enhanced mucus penetrability for oral delivery of siRNA. Biomater Sci. 2021;9(12):4260-4277.
|
[[78]] |
Cong M, Tan S, Li S, et al.Technology insight: plant-derived vesicles-how far from the clinical biotherapeutics and therapeutic drug carriers? Adv Drug Deliv Rev. 2022;182:114108.
|
[[79]] |
Chen YS, Lin EY, Chiou TW, et al. Exosomes in clinical trial and their production in compliance with good manufacturing practice. Tzu Chi Med J. 2019;32(2):113-120.
|
[[80]] |
Wang SS, Jia J, Wang Z.Mesenchymal stem cell-derived extracellular vesicles suppresses inos expression and ameliorates neural impairment in Alzheimer’s disease mice. [J] Alzheimers Dis. 2018;61(3):1005-1013.
|
[[81]] |
Teixeira FG, Carvalho MM, Panchalingam KM, et al.Impact of the secretome of human mesenchymal stem cells on brain structure and animal behavior in a rat model of Parkinson’s disease. Stem Cells Transl Med. 2017;6(2):634-646.
|
[[82]] |
Lee M, Liu T, Im W, et al.Exosomes from adipose-derived stem cells ameliorate phenotype of Huntington’s disease in vitro model. Eur [J] Neurosci. 2016;44(4):2114-2119.
|
[[83]] |
Bonafede R, Turano E, Scambi I, et al. ASC-exosomes ameliorate the disease progression in SOD1(G93A) murine model underlining their potential therapeutic use in human ALS. Int J Mol Sci. 2020;21(10):3651.
|
[[84]] |
Chang C, Lang H, Geng N, et al.Exosomes of BV-2 cells induced by alpha-synuclein: important mediator of neurodegeneration in PD. Neurosci Lett. 2013;548:190-195.
|
[[85]] |
Hong Y, Zhao T, Li XJ, et al.Mutant Huntingtin inhibits αB-crystallin expression and impairs exosome secretion from astrocytes. [J] Neurosci. 2017;37(39):9550-9563.
|
[[86]] |
Li P, Kaslan M, Lee SH, et al.Progress in exosome isolation techniques. Theranostics. 2017;7(3):789-804.
|
[[87]] |
Peng H, Ji W, Zhao R, et al. Exosome: a significant nano-scale drug delivery carrier. J Mater Chem B. 2020;8(34):7591-7608.
|
[[88]] |
Zempleni J, Aguilar-Lozano A, Sadri M, et al.Biological activities of extracellular vesicles and their cargos from bovine and human milk in humans and implications for infants. [J] Nutr. 2017;147(1):3-10.
|
[[89]] |
Chaput N, Théry C.Exosomes: immune properties and potential clinical implementations. Semin Immunopathol. 2011;33(5):419-440.
|
[[90]] |
Wang R, Wang X, Zhang Y, et al.Emerging prospects of extracellular vesicles for brain disease theranostics. [J] Control Release. 2022;341:844-868.
|
[[91]] |
Saintl J, Gosselet F, Duban-Deweer S, et al.Targeting and crossing the blood-brain barrier with extracellular vesicles. Cells. 2020;9(4):851.
|
[[92]] |
Matsumoto J, Stewart T, Banks WA, et al.The transport mechanism of extracellular vesicles at the blood-brain barrier. Curr Pharm Des. 2017;23(40):6206-6214.
|
[[93]] |
Kumar A, Zhou L, Zhi K, et al.Challenges in biomaterial-based drug delivery approach for the treatment of neurodegenerative diseases: opportunities for extracellular vesicles. Int [J] Mol Sci. 2020;22(1):138.
|
[[94]] |
Ren J, He W, Zheng L, et al.From structures to functions: insights into exosomes as promising drug delivery vehicles. Biomater Sci. 2016;4(6):910-921.
|
[[95]] |
Li L, Zhang L, Knez M.Comparison of two endogenous delivery agents in cancer therapy: exosomes and ferritin. Pharmacol Res. 2016;110:1-9.
|
[[96]] |
Walker S, Busatto S, Pham A.Extracellular vesicles-based drug delivery system for cancer treatment. Theranostics. 2019;9(26):8001-8017.
|
[[97]] |
Fu S, Wang Y, Xia X, et al.Exosome engineering: current progress in cargo loading and targeted delivery. NanoImpact. 2020;20:100261.
|
[[98]] |
Jia G, Han Y, An Y, et al.NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo. Biomaterials. 2018;178:302-316.
|
[[99]] |
Gong C, Tian J, Wang Z, et al. Functional exosome-mediated co-delivery of doxorubicin and hydrophobically modified microRNA 159 for triple-negative breast cancer therapy. J Nanobiotechnology. 2019;17(1):93.
|
[[100]] |
Liu C, Su C.Design strategies and application progress of therapeutic exosomes. Theranostics. 2019;9(4):1015-1028.
|
[[101]] |
Vader P, Kooijmans SA, Stremersch S, et al.New considerations in the preparation of nucleic acid-loaded extracellular vesicles. Ther Deliv. 2015;5(2):105-107.
|
[[102]] |
Aqil F, Jeyabalan J, Agrawal AK, et al.Exosomal delivery of berry anthocyanidins for the management of ovarian cancer. Food Funct. 2017;8(11):4100-4107.
|
[[103]] |
Amiot MJ, Romier B, Dao TMA, et al.Optimization of trans-resveratrol bioavailability for human therapy. Biochimie. 2013;95:1233-1238.
|
[[104]] |
Sergides C, Chirilă M, Silvestro L, et al.Bioavailability and safety study of resveratrol 500 mg tablets in healthy male and female volunteers. Exp Ther Med. 2016;11(1):164-170.
|
[[105]] |
Weiskirchen S, Weiskirchen R.Resveratrol: how much wine do you have to drink to stay healthy? Adv Nutr. 2016;7(4):706-718.
|
[[106]] |
Cottart CH, Nivet-Antoine V, Laguillier-Morizot C, et al.Resveratrol bioavailability and toxicity in humans. Mol Nutr Food Res. 2010;54:7-16.
|
[[107]] |
Anand P, Kunnumakkara AB, Newman RA, et al.Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807-818.
|
[[108]] |
Bhat A, Mahalakshmi AM, Ray B, et al.Benefits of curcumin in brain disorders. Biofactors. 2019;45(5):666-689.
|
[[109]] |
Purkayastha S, Berliner A, Fernando SS, et al.Curcumin blocks brain tumor formation. Brain Res. 2009;1266:130-138.
|
[[110]] |
Walle T.Bioavailability of resveratrol. Ann N Y Acad Sci. 2011;1215:9-15.
|
[[111]] |
Metzler M, Pfeiffer E, Schulz SI, et al.Curcumin uptake and metabolism. Biofactors. 2013;39(1):14-20.
|
[[112]] |
Czank C, Cassidy A, Zhang Q, et al. Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a (13)C-tracer study. Am J Clin Nutr. 2013;97(5):995-1003.
|
[[113]] |
Fornasaro S, Ziberna L, Gasperotti M, et al. Determination of cyanidin 3-glucoside in rat brain, liver and kidneys by UPLC/MS-MS and its application to a short-term pharmacokinetic study. Sci Rep. 2016;6:22815.
|
[[114]] |
Wang H, Sui HJ, Zheng Y, et al.Curcumin-primed exosomes potently ameliorate cognitive function in AD mice by inhibiting hyperphosphorylation of Tau protein through the AKT/GSK-3β pathway. Nanoscale. 2019;11(15):7481-7496.
|
[[115]] |
Fan Y, Li Y, Huang S, et al.Resveratrol-primed exosomes strongly promote the recovery of motor function in SCI rats by activating autophagy and inhibiting apoptosis via the PI3K signaling pathway. Neurosci Lett. 2020;736:135262.
|
[[116]] |
Huo Q, Shi Y, Qi Y, et al.Biomimetic silibinin-loaded macrophage-derived exosomes induce dual inhibition of Aβ aggregation and astrocyte activation to alleviate cognitive impairment in a model of Alzheimer’s disease. Mater Sci Eng C Mater Biol Appl. 2021;129:112365.
|
[[117]] |
Peng H, Li Y, Ji W, et al.Intranasal administration of self-oriented nanocarriers based on therapeutic exosomes for synergistic treatment of Parkinson’s disease. ACS Nano. 2022;16(1):869-884.
|
[[118]] |
Qi Y, Guo L, Jiang Y, et al.Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles. Drug Deliv. 2020;27(1):745-755.
|
[[119]] |
Gao ZS, Zhang CJ, Xia N, et al.Berberine-loaded M2 macrophage-derived exosomes for spinal cord injury therapy. Acta Biomater. 2021;126:211-223.
|
[[120]] |
Priyadarsini KI.The chemistry of curcumin: from extraction to therapeutic agent. Molecules. 2014;19(12):20091-20112.
|
[[121]] |
Kalani A, Chaturvedi P.Curcumin-primed and curcumin-loaded exosomes: potential neural therapy. Neural Regen Res. 2017;12(2):205-206.
|
[[122]] |
Guijarro-Leach J, Keogh A, Durban V, et al.Characterisation of ExoPr0 exosomes derived from proliferating GMP-grade CTX cells. Cytotherapy. 2018;20(5):S22.
|
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