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A review of the neuroprotective effects of andrographolide in Alzheimer's disease

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Abstract

Alzheimer’s disease, characterized by amyloid beta peptides and neurofibrillary tangles, is the most prevalent cause of dementia. Nowadays, some novel medicines being developed have displayed more illustrious therapeutic efficacies in Alzheimer’s disease. Recent studies have found andrographolide exhibiting therapeutic efficacy in a variety of Alzheimer’s disease models. Andrographolide is a traditional herbal medicine compound extracted from Andrographis paniculata. Evidence has shown that andrographolide reduces amyloid beta aggregation and suppresses neuroinflammatory response and synaptic dysfunction by reversing the microglia-mediated production of pro-inflammatory cytokines as well as Alzheimer’s disease-associated reduction in synaptic proteins. In the present review, the pharmacological effects of andrographolide are summarized and its mechanism of action against Alzheimer’s disease is discussed to discover the possibilities of andrographolide for Alzheimer’s disease prevention and therapy.

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References

  • Abedi Z, Khaza’ai H, Vidyadaran S, Mutalib MSA (2017) The modulation of NMDA and AMPA/kainate receptors by tocotrienol-rich fraction and α-tocopherol in glutamate-induced injury of primary astrocytes. Biomedicines 5(4):68

    Article  PubMed Central  Google Scholar 

  • Al-Hilaly YK, Pollack SJ, Vadukul DM, Citossi F, Rickard JE, Simpson M, Serpell LC (2017) Alzheimer’s disease-like paired helical filament assembly from truncated tau protein is independent of disulfide crosslinking. J Mol Biol 429(23):3650–3665

    Article  CAS  PubMed  Google Scholar 

  • Alonso AD, Cohen LS, Corbo C, Morozova V, ElIdrissi A, Phillips G, Kleiman FE (2018) Hyperphosphorylation of tau associates with changes in its function beyond microtubule stability. Front Cell Neurosci 12:338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Antunes M, Biala G (2012) The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process 13(2):93–110

    Article  CAS  PubMed  Google Scholar 

  • Ardiles ÁO, Tapia-Rojas CC, Mandal M, Alexandre F, Kirkwood A, Inestrosa NC, Palacios AG (2012) Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer’s disease. Proc Natl Acad Sci 109(34):13835–13840

    Article  CAS  PubMed  Google Scholar 

  • Bao Z, Guan S, Cheng C, Wu S, Wong SH, Kemeny DM, Wong WF (2009) A novel antiinflammatory role for andrographolide in asthma via inhibition of the nuclear factor-κB pathway. Am J Respir Crit Care Med 179(8):657–665

    Article  CAS  PubMed  Google Scholar 

  • Bera R, Ahmed SM, Sarkar L, Sen T, Karmakar S (2014) Pharmacokinetic analysis and tissue distribution of andrographolide in rat by a validated LC-MS/MS method. Pharm Biol 52(3):321–329

    Article  CAS  PubMed  Google Scholar 

  • Brandt R, Trushina NI, Bakota L, Mulkidjanian AY (2019) The evolution of tau phosphorylation and interactions. Front Aging Neurosci 11:256

    Article  PubMed  PubMed Central  Google Scholar 

  • Brown MF, Giumetti GW (2006) Spatial pattern learning in the radial arm maze. Learn Behav 34(1):102–108

    Article  PubMed  Google Scholar 

  • Chen Y-Y, Hsu M-J, Hsieh C-Y, Lee L-W, Chen Z-C, Sheu J-R (2014) Andrographolide inhibits nuclear factor-B activation through JNK-Akt-p65 signaling cascade in tumor necrosis factor-α-Stimulated vascular smooth muscle cells. Sci World J 2014:1–14

    Google Scholar 

  • Chong FP, Ng KY, Koh RY, Chye SM (2018) Tau proteins and tauopathies in Alzheimer’s disease. Cell Mol Neurobiol 38(5):965–980

    Article  CAS  PubMed  Google Scholar 

  • Collingridge GL, Peineau S, Howland JG, Wang YT (2010) Long-term depression in the CNS. Nat Rev Neurosci 11(7):459–473

    Article  CAS  PubMed  Google Scholar 

  • Das S, Mishra K, Ganju L, Singh S (2017) Andrographolide-A promising therapeutic agent, negatively regulates glial cell derived neurodegeneration of prefrontal cortex, hippocampus and working memory impairment. J Neuroimmunol 313:161–175

    Article  CAS  PubMed  Google Scholar 

  • Delgado JY (2020). An Alternative Pin1 Binding and Isomerization Site in the N-Terminus Domain of PSD-95. Frontiers in Molecular Neuroscience, 13.

  • Ding Y, Shi C, Chen L, Ma P, Li K, Jin J, Li A (2017) Effects of andrographolide on postoperative cognitive dysfunction and the association with NF-κB/MAPK pathway. Oncol Lett 14(6):7367–7373

    PubMed  PubMed Central  Google Scholar 

  • Gray SC, Kinghorn KJ, Woodling NS (2020) Shifting equilibriums in Alzheimer’s disease: the complex roles of microglia in neuroinflammation, neuronal survival and neurogenesis. Neural Regen Res 15(7):1208–1219

    Article  PubMed  PubMed Central  Google Scholar 

  • Gruber J, Ng LF, Fong S, Wong YT, Koh SA, Chen C-B, Wenk MR (2011) Mitochondrial changes in ageing Caenorhabditis elegans–what do we learn from superoxide dismutase knockouts? PLoS ONE 6(5):e19444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guimaraes Marques MJ, Reyes-Garcia SZ, Marques-Carneiro JE, Lopes-Silva LB, Andersen ML, Cavalheiro EA, Scorza CA (2018) Long-term potentiation decay and poor long-lasting memory process in the wild rodents Proechimys from brazil’s amazon rainforest. Front Behav Neurosci 12:2

    Article  PubMed  PubMed Central  Google Scholar 

  • Guo W, Liu W, Chen G, Hong S, Qian C, Xie N, Xu Q (2012) Water-soluble andrographolide sulfonate exerts anti-sepsis action in mice through down-regulating p38 MAPK, STAT3 and NF-κB pathways. Int Immunopharmacol 14(4):613–619

    Article  CAS  PubMed  Google Scholar 

  • Harrison FE, Reiserer RS, Tomarken AJ, McDonald MP (2006) Spatial and nonspatial escape strategies in the Barnes maze. Learn Mem 13(6):809–819

    Article  PubMed  PubMed Central  Google Scholar 

  • Inestrosa NC, Ríos JA, Cisternas P, Tapia-Rojas C, Rivera DS, Braidy N, Ardiles AO (2015) Age progression of neuropathological markers in the brain of the chilean rodent octodon degus, a natural model of Alzheimer’s disease. Brain Pathol 25(6):679–691

    Article  CAS  PubMed  Google Scholar 

  • Iruretagoyena MI, Sepúlveda SE, Lezana JP, Hermoso M, Bronfman M, Gutiérrez MA, Kalergis AM (2006) Inhibition of nuclear factor-κB enhances the capacity of immature dendritic cells to induce antigen-specific tolerance in experimental autoimmune encephalomyelitis. J Pharmacol Exp Ther 318(1):59–67

    Article  CAS  PubMed  Google Scholar 

  • Islam MT (2017) Andrographolide, a new hope in the prevention and treatment of metabolic syndrome. Front Pharmacol 8:571

    Article  PubMed  PubMed Central  Google Scholar 

  • Italiani P, Puxeddu I, Napoletano S, Scala E, Melillo D, Manocchio S, Vitale E (2018) Circulating levels of IL-1 family cytokines and receptors in Alzheimer’s disease: new markers of disease progression? J Neuroinflammation 15(1):1–12

    Article  Google Scholar 

  • Jašarević E, Sieli PT, Twellman EE, Welsh TH, Schachtman TR, Roberts RM, Rosenfeld CS (2011) Disruption of adult expression of sexually selected traits by developmental exposure to bisphenol A. Proc Natl Acad Sci 108(28):11715–11720

    Article  PubMed  Google Scholar 

  • Jaworski T, Banach-Kasper E, Gralec K (2019) GSK-3β at the intersection of neuronal plasticity and neurodegeneration. Neural plasticity 2019:1–14

    Article  Google Scholar 

  • Jones SV, Kounatidis I (2017) Nuclear factor-kappa B and Alzheimer disease, unifying genetic and environmental risk factors from cell to humans. Front Immunol 8:1805

    Article  PubMed  PubMed Central  Google Scholar 

  • Kalergis AM, Iruretagoyena MI, Barrientos MJ, González PA, Herrada AA, Leiva ED, Jacobelli SH (2009) Modulation of nuclear factor-κB activity can influence the susceptibility to systemic lupus erythematosus. Immunology 128(12):e306–e314

    Article  PubMed  PubMed Central  Google Scholar 

  • Kou X, Chen D, Chen N (2019) Physical activity alleviates cognitive dysfunction of Alzheimer’s disease through regulating the mtor signaling pathway. Int J Mol Sci 20(7):1591

    Article  CAS  PubMed Central  Google Scholar 

  • Kumar V, Thakur A, Chatterjee S (2014) Perspective of Andrographis paniculata in neurological disorders. Clinic Pharmacol Biopharmaceut S 2:2

    Google Scholar 

  • Kumazawa-Manita N, Hama H, Miyawaki A, Iriki A (2013). Tool use specific adult neurogenesis and synaptogenesis in rodent Octodon degus hippocampus. PLoS One, 8(3)

  • Lee JC, Tseng CK, Young KC, Sun HY, Wang SW, Chen WC, Wu YH (2014a) Andrographolide exerts anti-hepatitis C virus activity by up-regulating haeme oxygenase-1 via the p38 MAPK/N rf2 pathway in human hepatoma cells. Br J Pharmacol 171(1):237–252

    Article  CAS  PubMed  Google Scholar 

  • Lee T-Y, Chang H-H, Wen C-K, Huang T-H, Chang Y-S (2014b) Modulation of thioacetamide-induced hepatic inflammations, angiogenesis and fibrosis by andrographolide in mice. J Ethnopharmacol 158:423–430

    Article  CAS  PubMed  Google Scholar 

  • Lee H, Shin W, Kim K, Lee S, Lee EJ, Kim J, Kang M (2019) NGL-3 in the regulation of brain development, Akt/GSK3b signaling, long-term depression, and locomotive and cognitive behaviors. PLoS biology, 17(6).

  • Li J, Luo L, Wang X, Liao B, Li G (2009) Inhibition of NF-κB expression and allergen-induced airway inflammation in a mouse allergic asthma model by andrographolide. Cell Mol Immunol 6(5):381–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y-J, Yu C-H, Li J-B, Wu X-Y (2013) Andrographolide antagonizes cigarette smoke extract-induced inflammatory response and oxidative stress in human alveolar epithelial A549 cells through induction of microRNA-218. Exp Lung Res 39(10):463–471

    Article  CAS  PubMed  Google Scholar 

  • Li G-F, Qin Y-H, Du P-Q (2015) Andrographolide inhibits the migration, invasion and matrix metalloproteinase expression of rheumatoid arthritis fibroblast-like synoviocytes via inhibition of HIF-1α signaling. Life Sci 136:67–72

    Article  CAS  PubMed  Google Scholar 

  • Li C-X, Li H-G, Zhang H, Cheng R-H, Li M, Liang J-Y, Yu H (2016) Andrographolide suppresses thymic stromal lymphopoietin in phorbol myristate acetate/calcium ionophore A23187-activated mast cells and 2, 4-dinitrofluorobenzene-induced atopic dermatitis-like mice model. Drug Des Dev Ther 10:781

    Article  Google Scholar 

  • Li S, Jin M, Liu L, Dang Y, Ostaszewski BL, Selkoe DJ (2018) Decoding the synaptic dysfunction of bioactive human AD brain soluble Aβ to inspire novel therapeutic avenues for Alzheimer’s disease. Acta Neuropathol Commun 6(1):1–16

    Article  Google Scholar 

  • Liao W, Tan WD, Wong WF (2016) Andrographolide restores steroid sensitivity to block lipopolysaccharide/IFN-γ–induced IL-27 and airway hyperresponsiveness in mice. J Immunol 196(11):4706–4712

    Article  CAS  PubMed  Google Scholar 

  • Liu W, Guo W, Guo L, Gu Y, Cai P, Xie N, Sun Y (2014) Andrographolide sulfonate ameliorates experimental colitis in mice by inhibiting Th1/Th17 response. Int Immunopharmacol 20(2):337–345

    Article  PubMed  Google Scholar 

  • Liu E, Xie A-J, Zhou Q, Li M, Zhang S, Li S, Wang J-Z (2017) GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory. Sci Rep 7(1):1–11

    Google Scholar 

  • Lively S, Schlichter LC (2018) Microglia responses to pro-inflammatory stimuli (LPS, IFNγ+ TNFα) and reprogramming by resolving cytokines (IL-4, IL-10). Front Cell Neurosci 12:215

    Article  PubMed  PubMed Central  Google Scholar 

  • Lu C-Y, Li C-C, Lii C-K, Yao H-T, Liu K-L, Tsai C-W, Chen H-W (2011) Andrographolide-induced pi class of glutathione S-transferase gene expression via PI3K/Akt pathway in rat primary hepatocytes. Food Chem Toxicol 49(1):281–289

    Article  CAS  PubMed  Google Scholar 

  • Lu WJ, Lin KH, Hsu MJ, Chou DS, Hsiao G, Sheu JR (2012) Suppression of NF-κB signaling by andrographolide with a novel mechanism in human platelets: regulatory roles of the p38 MAPK-hydroxyl radical-ERK2 cascade. Biochem Pharmacol 84(7):914–924

    Article  CAS  PubMed  Google Scholar 

  • Marcello E, Epis R, Saraceno C, Di Luca M (2012). Synaptic dysfunction in Alzheimer’s disease Synaptic Plasticity (pp. 573–601): Springer.

  • Marsh J, Alifragis P (2018) Synaptic dysfunction in Alzheimer’s disease: the effects of amyloid beta on synaptic vesicle dynamics as a novel target for therapeutic intervention. Neural Regen Res 13(4):616

    Article  PubMed  PubMed Central  Google Scholar 

  • Matoba K, Kawanami D, Tsukamoto M, Kinoshita J, Ito T, Ishizawa S, Matsufuji S (2014) Rho-kinase regulation of TNF-α-induced nuclear translocation of NF-κB RelA/p65 and M-CSF expression via p38 MAPK in mesangial cells. Am J Physiol Ren Physiol 307(5):F571–F580

    Article  CAS  Google Scholar 

  • Ming G-L, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250

    Article  CAS  PubMed  Google Scholar 

  • Mittal SP, Khole S, Jagadish N, Ghosh D, Gadgil V, Sinkar V, Ghaskadbi SS (2016). Andrographolide protects liver cells from H2O2 induced cell death by upregulation of Nrf-2/HO-1 mediated via adenosine A2a receptor signalling. Biochimica et Biophysica Acta (BBA)-General Subjects, 1860(11), 2377–2390.

  • Motyl J, Wencel P, Cieślik M, Strosznajder R, Strosznajder J (2018) Alpha-synuclein alters differently gene expression of Sirts, PARPs and other stress response proteins: implications for neurodegenerative disorders. Mol Neurobiol 55(1):727–740

    Article  CAS  PubMed  Google Scholar 

  • Nelson CD, Kim MJ, Hsin H, Chen Y, Sheng M (2013) Phosphorylation of threonine-19 of PSD-95 by GSK-3β is required for PSD-95 mobilization and long-term depression. J Neurosci 33(29):12122–12135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okhuarobo A, Falodun JE, Erharuyi O, Imieje V, Falodun A, Langer P (2014) Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology. Asian Pac J Trop Dis 4(3):213

    Article  CAS  PubMed Central  Google Scholar 

  • Palomer E, Buechler J, Salinas PC (2019) Wnt signalling deregulation in the ageing and Alzheimer´ s brain. Front Cell Neurosci 13:227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palop JJ, Mucke L (2010) Amyloid-β–induced neuronal dysfunction in Alzheimer’s disease: from synapses toward neural networks. Nat Neurosci 13(7):812–818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel S, Alam A, Pant R, Chattopadhyay S (2019). Wnt Signaling and Its Significance Within the Tumor Microenvironment: Novel Therapeutic Insights. Frontiers in Immunology, 10.

  • Peña-Ortega F (2013). Amyloid beta-protein and neural network dysfunction. Journal of Neurodegenerative Diseases, 2013.

  • Peng S, Gao J, Liu W, Jiang C, Yang X, Sun Y, Xu Q (2016) Andrographolide ameliorates OVA-induced lung injury in mice by suppressing ROS-mediated NF-κB signaling and NLRP3 inflammasome activation. Oncotarget 7(49):80262

    Article  PubMed  PubMed Central  Google Scholar 

  • Pérez MJ, Quintanilla RA (2015) 2015. Therapeutic actions of the thiazolidinediones in Alzheimer’s disease, PPAR research

    Google Scholar 

  • Pšemeneckienė G, Petrikonis K, Rastenytė D (2019) Polymorphisms of proinflammatory cytokines in relation to APOE epsilon 4 and risk of Alzheimer’s disease in the lithuanian population. Medicina 55(10):689

    Article  PubMed Central  Google Scholar 

  • Reis PA, de Albuquerque CFG, Gutierrez T, Silva AR, de Castro Faria Neto, H. (2017) Role of nitric oxide synthase in the function of the central nervous system under normal and infectious conditions. Nitric oxide synthase-simple enzyme-complex roles. London, InTech, pp 55–70

    Google Scholar 

  • Richetin K, Leclerc C, Toni N, Gallopin T, Pech S, Roybon L, Rampon C (2015) Genetic manipulation of adult-born hippocampal neurons rescues memory in a mouse model of Alzheimer’s disease. Brain 138(2):440–455

    Article  PubMed  Google Scholar 

  • Rivera DS, Inestrosa NC, Bozinovic F (2016a) On cognitive ecology and the environmental factors that promote Alzheimer disease: lessons from octodon degus (Rodentia: Octodontidae). Biol Res 49(1):10

    Article  PubMed  PubMed Central  Google Scholar 

  • Rivera DS, Lindsay C, Codocedo JF, Morel I, Pinto C, Cisternas P, Inestrosa NC (2016b) Andrographolide recovers cognitive impairment in a natural model of Alzheimer’s disease (Octodon degus). Neurobiol Aging 46:204–220

    Article  CAS  PubMed  Google Scholar 

  • Rosenfeld CS, Ferguson SA (2014). Barnes maze testing strategies with small and large rodent models. JoVE (Journal of Visualized Experiments)(84), e51194.

  • Roy DN, Sen G, Chowdhury KD, Biswas T (2011) Combination therapy with andrographolide and d-penicillamine enhanced therapeutic advantage over monotherapy with d-penicillamine in attenuating fibrogenic response and cell death in the periportal zone of liver in rats during copper toxicosis. Toxicol Appl Pharmacol 250(1):54–68

    Article  CAS  PubMed  Google Scholar 

  • Rubach MP, Zhang H, Florence SM, Mukemba JP, Kalingonji AR, Anstey NM, Mwaikambo ED (2019) Kinetic and cross-sectional studies on the genesis of hypoargininemia in severe pediatric Plasmodium falciparum malaria. Infect Immun 87(4):e00655-e618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salmeron KE, Maniskas ME, Edwards DN, Wong R, Rajkovic I, Trout A, Pinteaux E (2019) Interleukin 1 alpha administration is neuroprotective and neuro-restorative following experimental ischemic stroke. J Neuroinflammation 16(1):222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salvemini D, Kim SF, Mollace V (2013) Reciprocal regulation of the nitric oxide and cyclooxygenase pathway in pathophysiology: relevance and clinical implications. Am J Physiol Regul Integr Comp Physiol 304(7):R473–R487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sani D, Khatab NI, Kirby BP, Yong A, Hasan S, Basri H, Stanslas J (2019) A standardised andrographis paniculata Burm. Nees aqueous extract prevents Lipopolysaccharide-induced cognitive deficits through suppression of inflammatory cytokines and oxidative stress mediators. J Adv Res 16:87–97

    Article  CAS  PubMed  Google Scholar 

  • Selkoe DJ (2013) The therapeutics of Alzheimer’s disease: where we stand and where we are heading. Ann Neurol 74(3):328–336

    Article  CAS  PubMed  Google Scholar 

  • Seo JY, Pyo E, An JP, Kim J, Sung SH, Oh WK (2017). Andrographolide activates Keap1/Nrf2/ARE/HO-1 pathway in HT22 cells and suppresses microglial activation by Aβ42 through Nrf2-related inflammatory response. Mediators of inflammation, 2017.

  • Serrano FG, Tapia-Rojas C, Carvajal FJ, Hancke J, Cerpa W, Inestrosa NC (2014) Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice. Mol Neurodegener 9(1):61

    Article  PubMed  PubMed Central  Google Scholar 

  • Shao F, Tan T, Tan Y, Sun Y, Wu X, Xu Q (2016) Andrographolide alleviates imiquimod-induced psoriasis in mice via inducing autophagic proteolysis of MyD88. Biochem Pharmacol 115:94–103

    Article  CAS  PubMed  Google Scholar 

  • Sharma S, Rakoczy S, Brown-Borg H (2010) Assessment of spatial memory in mice. Life Sci 87(17–18):521–536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheng M, Kim E (2011) The postsynaptic organization of synapses. Cold Spring Harb Perspect Biol 3(12):a005678

    Article  PubMed  PubMed Central  Google Scholar 

  • Shih R-H, Wang C-Y, Yang C-M (2015) NF-kappaB signaling pathways in neurological inflammation: a mini review. Front Mol Neurosci 8:77

    Article  PubMed  PubMed Central  Google Scholar 

  • Silva-García O, Valdez-Alarcón JJ, Baizabal-Aguirre VM (2019) Wnt/β-catenin signaling as a molecular target by pathogenic bacteria. Front Immunol 10:2135

    Article  PubMed  PubMed Central  Google Scholar 

  • Singha PK, Roy S, Dey S (2007). Protective activity of andrographolide and arabinogalactan proteins from Andrographis paniculata Nees. against ethanol-induced toxicity in mice. Journal of Ethnopharmacology, 111(1):13–21.

  • Song Y, Kim H-D, Lee M-K, Hong I-H, Won C-K, Bai H-W, Cho J-H (2017). Maysin and its flavonoid derivative from Centipedegrass attenuates amyloid plaques by inducting humoral immune response with Th2 skewed cytokine response in the tg (APPswe, PS1dE9) Alzheimer’s mouse model. PloS one, 12(1).

  • Song Y, Hu M, Zhang J, Teng Z-Q, Chen C (2019) A novel mechanism of synaptic and cognitive impairments mediated via microRNA-30b in Alzheimer’s disease. EBioMedicine 39:409–421

    Article  PubMed  Google Scholar 

  • Soong TW, Liu C (2019) Nitric oxide, iron and neurodegeneration. Front Neurosci 13:114

    Article  PubMed  PubMed Central  Google Scholar 

  • Stakos DA, Stamatelopoulos K, Bampatsias D, Sachse M, Zormpas E, Vlachogiannis NI, Stellos K (2020) The Alzheimer’s disease amyloid-beta hypothesis in cardiovascular aging and disease: JACC focus seminar. J Am Coll Cardiol 75(8):952–967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Subedi L, Lee SE, Madiha S, Gaire BP, Jin M, Yumnam S, Kim SY (2020) Phytochemicals against TNFα-mediated neuroinflammatory diseases. Int J Mol Sci 21(3):764

    Article  CAS  PubMed Central  Google Scholar 

  • Sun Y, Ma J, Li D, Li P, Zhou X, Li Y, Luo X (2019) Interleukin-10 inhibits interleukin-1β production and inflammasome activation of microglia in epileptic seizures. J Neuroinflammation 16(1):66

    Article  PubMed  PubMed Central  Google Scholar 

  • Sunyer B, Patil S, Höger H, Luber G (2007). Barnes maze, a useful task to assess spatial reference memory in the mice. Protocol Exchange.

  • Takeda Y, Matoba K, Kawanami D, Nagai Y, Akamine T, Ishizawa S, Utsunomiya K (2019) ROCK2 regulates monocyte migration and cell to cell adhesion in vascular endothelial cells. Int J Mol Sci 20(6):1331

    Article  CAS  PubMed Central  Google Scholar 

  • Tan WD, Liao W, Zhou S, Wong WF (2017) Is there a future for andrographolide to be an anti-inflammatory drug? deciphering its major mechanisms of action. Biochem Pharmacol 139:71–81

    Article  CAS  PubMed  Google Scholar 

  • Tapia-Rojas C, Inestrosa NC (2018a) Loss of canonical Wnt signaling is involved in the pathogenesis of Alzheimer’s disease. Neural Regen Res 13(10):1705

    Article  PubMed  PubMed Central  Google Scholar 

  • Tapia-Rojas C, Inestrosa NC (2018b) Wnt signaling loss accelerates the appearance of neuropathological hallmarks of Alzheimer’s disease in J20-APP transgenic and wild-type mice. J Neurochem 144(4):443–465

    Article  CAS  PubMed  Google Scholar 

  • Tapia-Rojas C, Schüller A, Lindsay CB, Ureta RC, Mejías-Reyes C, Hancke J, Inestrosa NC (2015) Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3β: autoregulation of GSK-3β in vivo. Biochem J 466(2):415–430

    Article  CAS  PubMed  Google Scholar 

  • Tarragon E, Lopez D, Estrada C, Gonzalez-Cuello A, Ros CM, Lamberty Y, Guiso G (2014) Memantine prevents reference and working memory impairment caused by sleep deprivation in both young and aged Octodon degus. Neuropharmacology 85:206–214

    Article  CAS  PubMed  Google Scholar 

  • Tobore TO (2019). On the central role of mitochondria dysfunction and oxidative stress in Alzheimer’s disease. Neurological Sciences, 1–14.

  • Toledo E, Inestrosa N (2010) Activation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1ΔE9 mouse model of Alzheimer’s disease. Mol Psychiatry 15(3):272–285

    Article  CAS  PubMed  Google Scholar 

  • Tran QT, Tan WD, Wong WF, Chai CL (2020) Polypharmacology of andrographolide: beyond one molecule one target. Natural Product Reports.

  • Varela-Nallar L, Arredondo SB, Tapia-Rojas C, Hancke J, Inestrosa NC (2015) 2015. Andrographolide stimulates neurogenesis in the adult hippocampus, Neural plasticity

    Google Scholar 

  • Vargas L, Cerpa W, Muñoz F, Zanlungo S, Alvarez A (2018). Amyloid-β oligomers synaptotoxicity: The emerging role of EphA4/c-Abl signaling in Alzheimer's disease. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1864(4):1148–1159.

  • Visen P, Shukia B, Patnaik G, Dhawan B (1993) Andrographolide protects rat hepatocytes against paracetamol-induced damage. J Ethnopharmacol 40(2):131–136

    Article  CAS  PubMed  Google Scholar 

  • Wang T, Liu B, Zhang W, Wilson B, Hong J-S (2004) Andrographolide reduces inflammation-mediated dopaminergic neurodegeneration in mesencephalic neuron-glia cultures by inhibiting microglial activation. J Pharmacol Exp Ther 308(3):975–983

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Kastanenka KV, Arbel-Ornath M, Commins C, Kuzuya A, Lariviere AJ, Bacskai BJ (2018) An acute functional screen identifies an effective antibody targeting amyloid-β oligomers based on calcium imaging. Sci Rep 8(1):1–15

    Google Scholar 

  • Wang L, Cao F, Zhu L-L, Liu P, Shang Y-R, Liu W-H, Wang Z-Y (2019) Andrographolide impairs alpha-naphthylisothiocyanate-induced cholestatic liver injury in vivo. J Nat Med 73(2):388–396

    Article  CAS  PubMed  Google Scholar 

  • Xia Y-F, Ye B-Q, Li Y-D, Wang J-G, He X-J, Lin X, Hebbel RP (2004) Andrographolide attenuates inflammation by inhibition of NF-κB activation through covalent modification of reduced cysteine 62 of p50. J Immunol 173(6):4207–4217

    Article  CAS  PubMed  Google Scholar 

  • Xing B, Li Y-C, Gao W-J (2016) GSK3 β hyperactivity during an early critical period impairs prefrontal synaptic plasticity and induces lasting deficits in spine morphology and working memory. Neuropsychopharmacology 41(13):3003–3015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu D, Hou K, Li F, Chen S, Fang W, Li Y (2019a) XQ-1H alleviates cerebral ischemia in mice through inhibition of apoptosis and promotion of neurogenesis in a Wnt/β-catenin signaling dependent way. Life Sci 235:116844

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Tang D, Wang J, Wei H, Gao J (2019b) Neuroprotection of andrographolide against microglia-mediated inflammatory injury and oxidative damage in PC12 neurons. Neurochem Res 44(11):2619–2630

    Article  CAS  PubMed  Google Scholar 

  • Yan J, Chen Y, He C, Yang Z-Z, Lü C, Chen X-S (2012) Andrographolide induces cell cycle arrest and apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes. Cell Biol Toxicol 28(1):47–56

    Article  CAS  PubMed  Google Scholar 

  • Yang D, Zhang W, Song L, Guo F (2013) Andrographolide protects against cigarette smoke-induced lung inflammation through activation of Heme Oxygenase-1. J Biochem Mol Toxicol 27(5):259–265

    Article  CAS  PubMed  Google Scholar 

  • Yang C-H, Yen T-L, Hsu C-Y, Thomas P-A, Sheu J-R, Jayakumar T (2017a) Multi-targeting andrographolide, a novel NF-κB inhibitor, as a potential therapeutic agent for stroke. Int J Mol Sci 18(8):1638

    Article  PubMed Central  Google Scholar 

  • Yang R, Liu S, Zhou J, Bu S, Zhang J (2017b) Andrographolide attenuates microglia-mediated Aβ neurotoxicity partially through inhibiting NF-κB and JNK MAPK signaling pathway. Immunopharmacol Immunotoxicol 39(5):276–284

    Article  CAS  PubMed  Google Scholar 

  • Yen T-L, Chen R-J, Jayakumar T, Lu W-J, Hsieh C-Y, Hsu M-J, Lin K-H (2016) Andrographolide stimulates p38 mitogen-activated protein kinase–nuclear factor erythroid-2-related factor 2–heme oxygenase 1 signaling in primary cerebral endothelial cells for definite protection against ischemic stroke in rats. Transl Res 170:57–72

    Article  CAS  PubMed  Google Scholar 

  • Yin J-N, Li Y-N, Gao Y, Li S-B, Li J-D (2015) Andrographolide plays an important role in bleomycin-induced pulmonary fibrosis treatment. Int J Clin Exp Med 8(8):12374

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yokokawa K, Iwahara N, Hisahara S, Emoto MC, Saito T, Suzuki H, Suzuki S (2019). Transplantation of mesenchymal stem cells improves Amyloid-β pathology by modifying microglial function and suppressing oxidative stress. Journal of Alzheimer's Disease(Preprint), 72(3):1–18.

  • Zhang C, Gui L, Xu Y, Wu T, Liu D (2013) Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance. Int Immunopharmacol 16(4):451–456

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Lai D, Wang L, Yu P, Zhu L, Guo B, Lee SMY (2014) Neuroprotective effects of the andrographolide analogue AL-1 in the MPP+/MPTP-induced Parkinson’s disease model in vitro and in mice. Pharmacol Biochem Behav 122:191–202

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Wang M, Li Y, Dong W (2018) Andrographolide attenuates viral myocarditis through interactions with the IL-10/STAT3 and P13K/AKT/NF-κβ signaling pathways. Exp Ther Med 16(3):2138–2143

    PubMed  PubMed Central  Google Scholar 

  • Zhu T, Wang D-X, Zhang W, Liao X-Q, Guan X, Bo H, Zhang Y-K (2013a) Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-κB. PLoS ONE 8(2):e56407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu T, Zhang W, Xiao M, Chen H, Jin H (2013b) Protective role of andrographolide in bleomycin-induced pulmonary fibrosis in mice. Int J Mol Sci 14(12):23581–23596

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Faculty of Medicine and Health Science, University Putra Malaysia, 43400, Serdang, Selangor, Malaysia

    Zahra Abedi, Hamidon Basri, Liyana Najwa Inche Mat, Huzwah Khaza’ai & Nur Afiqah Mohamad

  2. Centre for Drug Research, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia

    Zurina Hassan

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  1. Zahra Abedi
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  2. Hamidon Basri
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  3. Zurina Hassan
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  4. Liyana Najwa Inche Mat
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  5. Huzwah Khaza’ai
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  6. Nur Afiqah Mohamad
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ZA wrote the manuscript. All authors contributed to and approved the final manuscript.

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Correspondence to Hamidon Basri.

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This article does not contain any studies involving animals performed by any of the authors. This article does not contain any studies involving human participants performed by any of the authors.

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Zahra Abedi has no conflict of interest. Hamidon Basri has no conflict of interest. Zurina Hassan has no conflict of intrest. Liyana Najwa Inche Mat has no conflict of ineterest. Huzwah Khaza’ai has no conflict of interest. Nur Afiqah Mohamad has no conflict of interest.

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Abedi, Z., Basri, H., Hassan, Z. et al. A review of the neuroprotective effects of andrographolide in Alzheimer's disease. ADV TRADIT MED (ADTM) 21, 253–266 (2021). https://doi.org/10.1007/s13596-021-00573-8

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  • DOI: https://doi.org/10.1007/s13596-021-00573-8

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