Ahmad W, Ebert PR (2017) Metformin attenuates Aβ pathology mediated through levamisole sensitive nicotinic acetylcholine receptors in a C. Elegans model of Alzheimer’s disease. Mol Neurobiol 54:5427–5439

Article  CAS  PubMed  Google Scholar 

Ahmad R, Khan A, Rehman IU, Lee HJ, Khan I, Kim MO (2022) Lupeol treatment attenuates activation of glial cells and oxidative-stress-mediated neuropathology in mouse model of traumatic brain Injury. Int J Mol Sci 23(11):6086

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ahmed S, Mahmood Z, Javed A, Hashmi SN, Zerr I, Zafar S, Zahid S (2017) Effect of metformin on adult hippocampal neurogenesis: comparison with donepezil and links to cognition. J Mol Neurosci 62:88–98

Article  CAS  PubMed  Google Scholar 

Akhtar A, Dhaliwal J, Sah SP (2021) 7, 8-Dihydroxyflavone improves cognitive functions in ICV-STZ rat model of sporadic Alzheimer’s disease by reversing oxidative stress, mitochondrial dysfunction, and insulin resistance. Psychopharmacology 238:1991–2009

Article  CAS  PubMed  Google Scholar 

Araujo WL, Nunes-Nesi AD, Nikoloski Z, Sweetlove LJ, Fernie AR (2012) Metabolic control and regulation of the tricarboxylic acid cycle in photosynthetic and heterotrophic plant tissues. Plant Cell Environ 35(1):1–21

Badshah H, Ali T, Rehman SU, Amin FU, Ullah F, Kim TH, Kim MO (2016) Protective effect of lupeol against lipopolysaccharide-induced neuroinflammation via the p38/c-Jun N-terminal kinase pathway in the adult mouse brain. J Neuroimmune Pharmacol 11:48–60

Article  PubMed  Google Scholar 

Banchroft JD, Stevens A, Turner DR (1996) Theory and practice of histological techniques, Fourth ed. Churchil Livingstone, New York, London, San Francisco, Tokyo

Ben nejma A, Besbes M, Guérineau V, Touboul D (2017) Isolation and structure elucidation of acetylcholinesterase lipophilic lupeol derivatives inhibitors from the latex of the Tunisian Periploca laevigata. Arab J Chem 10:S2767–S2772

Article  CAS  Google Scholar 

Beutler E, Kelly BM (1963) The effect of sodium nitrite on red cell. GSH Experientia 19(2):96–97

Article  CAS  PubMed  Google Scholar 

Bhatia P, Singh N (2021) Thromboxane A2 synthase inhibition ameliorates endothelial dysfunction, memory deficits, oxidative stress and neuroinflammation in rat model of Streptozotocin diabetes induced dementia. Physiol Behav 241:113592

Article  CAS  PubMed  Google Scholar 

Brandes MS, Gray NE (2020) NRF2 as a therapeutic target in neurodegenerative diseases. ASN Neuro 12:1759091419899782. https://doi.org/10.1177/1759091419899782

Cheang WS, Tian XY, Wong WT, Lau CW, Lee SS, Chen ZY, Yao X, Wang N, Huang Y (2014) Metformin protects endothelial function in diet-induced obese mice by inhibition of endoplasmic reticulum stress through 5′ adenosine monophosphate–activated protein kinase–peroxisome proliferator–activated receptor δ pathway. Arterioscler Thromb Vasc Biol 34(4):830–836

Article  CAS  PubMed  Google Scholar 

Dinkova-Kostova AT, Kostov RV, Kazantsev AG (2018) The role of Nrf2 signaling in counteracting neurodegenerative diseases. FEBS J 285(19):3576–3590

Article  CAS  PubMed  PubMed Central  Google Scholar 

DiTacchio KA, Heinemann SF, Dziewczapolski G (2015) Metformin treatment alters memory function in a mouse model of Alzheimer’s disease. J Alzheimers Dis 44(1):43–48

Article  CAS  PubMed  PubMed Central  Google Scholar 

Farr SA, Roesler E, Niehoff ML, Roby DA, McKee A, Morley JE (2019) Metformin improves learning and memory in the SAMP8 mouse model of Alzheimer’s disease. J Alzheimers Dis 68(4):1699–1710

Article  CAS  PubMed  Google Scholar 

Feng Y, Wang X (2012). Antioxidant therapies for Alzheimer's disease. Oxid Med Cell Longev 2012:472932. https://doi.org/10.1155/2012/472932

Ganguly U, Kaur U, Chakrabarti SS, Sharma P, Agrawal BK, Saso L, Chakrabarti S (2021) Oxidative stress, neuroinflammation, and NADPH oxidase: implications in the pathogenesis and treatment of Alzheimer’s disease. Oxidative Med Cell Longev 2021:1–9

Article  Google Scholar 

Grisham MB, Benoit JN, Granger DN (1990) Assessment of leukocyte involvement during ischemia and reperfusion of intestine. Methods Enzymol 186:729–742

Article  CAS  PubMed  Google Scholar 

Gurovic MS, Castro MJ, Richmond V, Faraoni MB, Maier MS, Murray AP (2010) Triterpenoids with acetylcholinesterase inhibition from Chuquiraga Erinacea D. Don. subsp. erinacea (Asteraceae). Planta Med 76(06):607–610

Article  CAS  PubMed  Google Scholar 

Gurupriya S, Cathrine L, Ramesh J (2018) In vitro antidiabetic and antioxidant activities of lupeol isolated from the methanolic extract of Andrographis echioides leaves. J Pharmacogn Phytochem 7(4):768–775

Hadjira S, Mansour A, Seghiri R, Menad A, Benayache F, Benayache S, Ameddah S (2021) Neuroinflammation and behavioral deficit in rotenone-induced neurotoxicity in rats and the possible effects of butanolic extract of Centaurea Africana. Recent Adv Inflamm Allergy Drug Discovery 15(1):35–43

Article  CAS  Google Scholar 

https://www.who.int/news-room/fact-sheets/detail/dementia. Accessed Jan 2022

Huang S, Mo C, Zeng T, Lai Y, Zhou C, Xie S, Chen L, Wang Y, Chen Y, Huang S, Gao L (2021) Lupeol ameliorates LPS/D-GalN induced acute hepatic damage by suppressing inflammation and oxidative stress through TGFβ1-Nrf2 signal pathway. Aging 13(5):6592

Article  CAS  PubMed  PubMed Central  Google Scholar 

Johnson DA, Johnson JA (2015) Nrf2—a therapeutic target for the treatment of neurodegenerative diseases. Free Radic Biol Med 88:253–267

Article  CAS  PubMed  PubMed Central  Google Scholar 

Katila N, Bhurtel S, Shadfar S, Srivastav S, Neupane S, Ojha U, Jeong GS, Choi DY (2017) Metformin lowers α-synuclein phosphorylation and upregulates neurotrophic factor in the MPTP mouse model of Parkinson’s disease. Neuropharmacology 125:396–407

Article  CAS  PubMed  Google Scholar 

Katila N, Bhurtel S, Park PH, Choi DY (2021) Metformin attenuates rotenone-induced oxidative stress and mitochondrial damage via the AKT/Nrf2 pathway. Neurochem Int 148:105120

Article  CAS  PubMed  Google Scholar 

Khezri MR, Yousefi K, Mahboubi N, Hodaei D, Ghasemnejad-Berenji M (2022) Metformin in Alzheimer’s disease: an overview of potential mechanisms, preclinical and clinical findings. Biochem Pharmacol 5:114945

Klann IP, Martini F, Rosa SG, Nogueira CW (2020) Ebselen reversed peripheral oxidative stress induced by a mouse model of sporadic Alzheimer’s disease. Mol Biol Rep 47:2205–2215

Article  CAS  PubMed  Google Scholar 

Kumar A, Singh N (2017) Inhibitor of Phosphodiestearse-4 improves memory deficits, oxidative stress, neuroinflammation and neuropathological alterations in mouse models of dementia of Alzheimer’s type. Biomed Pharmacother 88:698–707

Article  CAS  PubMed  Google Scholar 

Kumar A, Singh N (2018) Calcineurin inhibition and protein kinase A activation limits cognitive dysfunction and histopathological damage in a model of dementia of the Alzheimer’s type. Curr Neurovasc Res 15(3):234–245

Article  CAS  PubMed  Google Scholar 

Liu K, Zhang X, Xie L, Deng M, Chen H, Song J, Long J, Li X, Luo J (2021) Lupeol and its derivatives as anticancer and anti-inflammatory agents: Molecular mechanisms and therapeutic efficacy. Pharmacol Res 164:105373. https://doi.org/10.1016/j.phrs.2020.105373

Lowry O, Rosebrough N, Farr A, Randall R (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

Article  CAS  PubMed  Google Scholar 

Lu M, Su C, Qiao C, Bian Y, Ding J, Hu G (2016) Metformin prevents dopaminergic neuron death in MPTP/P-Induced mouse model of Parkinson's disease via autophagy and mitochondrial ROS clearance. Int J Neuropsychopharmacol 19(9):pyw047. https://doi.org/10.1093/ijnp/pyw047

Ma Q (2013) Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426

Article  CAS  PubMed  PubMed Central  Google Scholar 

Madhu LN, Kodali M, Shetty AK (2022) Promise of metformin for preventing age-related cognitive dysfunction. Neural Regeneration Res 17(3):503

Article  CAS  Google Scholar 

Markowicz-Piasecka M, Sikora J, Szydłowska A, Skupień A, Mikiciuk-Olasik E, Huttunen KM (2017) Metformin–A future therapy for neurodegenerative diseases: theme: drug discovery, development and delivery in Alzheimer’s disease Guest Editor: Davide Brambilla. Pharm Res 34:2614–2627

Article  CAS  PubMed  PubMed Central  Google Scholar 

Merelli A, Repetto M, Lazarowski A, Auzmendi J (2021) Hypoxia, oxidative stress, and inflammation: three faces of neurodegenerative diseases. J Alzheimers Dis 82(s1):S109–S126

Article  CAS