Baicalein's neuroprotective effects in a lansoprazole-induced Alzheimer's model in Wistar rats
DOI:
https://doi.org/10.15584/ejcem.2025.4.5Keywords:
Alzheimer disease, anti-inflammatory, baicalein, lansoprazole, oxidative stressAbstract
Introduction and aim. Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most frequently diagnosed type of dementia. Baicalein, a flavonoid found in the roots of Scutellaria baicalensis, was useful in preventing neuronal injury in various neurodegenerative models. The present study was designed to determine the neuroprotective effect of baicalein in lansoprazole-induced AD in Wistar rats.
Material and methods. We used male Wistar rats randomly divided into six groups: control, vehicle, lansoprazole-induced, and baicalein+lansoprazole or baicalein treated. The lowest dose, lansoprazole (30 mg/kg), was administered orally for 28 weeks to induce AD-like pathology. Baicalein (10 mg/kg) was coadministered with lansoprazole in the treatment group. Cognitive functions were evaluated using a Morris water maze (MWM) and a novel object recognition test. Acetylcholinesterase (AChE) activity, determination of oxidative stress, including malondialdehyde, superoxide dismutas, and reduced glutathione levels, and inflammation-related cytokines such as tumor necrosis factor α were biochemically analyzed. We collected hippocampal sections to assess amyloid beta deposition and neuronal integrity histochemically.
Results. Lansoprazole-induced rats showed marked cognitive decline accompanied by enhanced AChE activity, increased oxidative stress, and levels of pro-inflammatory cytokines compared to controls (p<0.01). Co-administration of Baicalein significantly improved cognitive performance, AChE activity was reduced to control levels, oxidative stress markers decreased to near-normal values in the brain and blood, and inflammatory cytokines were significantly lower compared to rats treated with the lansoprazole-treated rats (p<0.01). Baicalein treatment attenuated plaque deposition and neuronal injury, as revealed by histopathological analysis in vivo.
Conclusion. Baicalein has a protective effect on lansoprazole-induced AD in Wistar rats. These appear to be due to the flavonoid's antioxidative, anti-inflammatory, and enzyme-inhibiting activities on AChE. These results propose baicalein as a potential therapeutic agent for further study with respect to prevention and treatment, especially in patients under long-term administration of proton pump inhibitors.
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References
Vatanabe IP, Manzine PR, Cominetti MR. Historic concepts of dementia and Alzheimer's disease: From ancient times to the present. Rev Neurol (Paris). 2020;176(3):140-147. doi: 10.1016/j.neurol.2019.03.004
Bondi MW, Edmonds EC, Salmon DP. Alzheimer's disease: past, present, and future. J Int Neuropsychol Soc. 2017;23(9-10):818-831. doi: 10.1017/S135561771700100X
Suresh S, Singh SA, Rushendran R, Vellapandian C, Prajapati B. Alzheimer's disease: the role of extrinsic factors in its development, an investigation of the environmental enigma. Front Neurol. 2023;14:1303111. doi: 10.3389/fneur.2023.1303111
Bagyinszky E, Giau VV, Shim K, Suk K, An SSA, Kim S. Role of inflammatory molecules in the Alzheimer's disease progression and diagnosis. J Neurol Sci. 2017;376:242-254. doi: 10.1016/j.jns.2017.03.031
Cummings J, Lee G, Mortsdorf T, Ritter A, Zhong K. Alzheimer's disease drug development pipeline: 2017. Alzheimers Dement (NY). 2017;3(3):367-384. doi: 10.1016/j.trci.2017.05.002
Liedtke C, Luedde T, Sauerbruch T, et al. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects. Fibrogenesis Tissue Repair. 2013;6(1):19. doi: 10.1186/1755-1536-6-19
Van der Flier WM, de Vugt ME, Smets EMA, Blom M, Teunissen CE. Towards a future where Alzheimer's disease pathology is stopped before the onset of dementia. Nat Aging. 2023;3(5):494-505. doi: 10.1038/s43587-023-00404-2
Tripathi PN, Srivastava P, Sharma P, Seth A, Shrivastava SK. Design and development of novel N-(pyrimidin-2-yl)-1,3,4-oxadiazole hybrids to treat cognitive dysfunctions. Bioorg Med Chem. 2019;27(7):1327-1340. doi: 10.1016/j.bmc.2019.02.031
Trejo-Lopez JA, Yachnis AT, Prokop S. Neuropathology of Alzheimer's Disease. Neurotherapeutics. 2022;19(1):173-185. doi: 10.1007/s13311-021-01146-y
Corsonello A, Lattanzio F. Cardiovascular and non-cardiovascular concerns with proton pump inhibitors: Are they safe? Trends Cardiovasc Med. 2019;29(6):353-360. doi: 10.1016/j.tcm.2018.10.008
Li H, Meng L, Liu F, Wei JF, Wang YQ. H+/K+-ATPase inhibitors: a patent review. Expert Opin Ther Pat. 2013;23(1):99-111. doi: 10.1517/13543776.2013.741121
Futai M, Sun-Wada GH, Wada Y, Matsumoto N, Nakanishi-Matsui M. Vacuolar-type ATPase: A proton pump to lysosomal trafficking. Proc Jpn Acad Ser B Phys Biol Sci. 2019;95(6):261-277. doi: 10.2183/pjab.95.018
Sharma P, Giri A, Tripathi PN. Emerging trends: neurofilament biomarkers in precision neurology. Neurochem Res. 2024;49(12):3208-3225. doi: 10.1007/s11064-024-04244-3
Tripathi PN, Lodhi A, Rai SN, et al. Review of pharmacotherapeutic targets in Alzheimer's disease and its management using traditional medicinal plants. Degener Neurol Neuromuscul Dis. 2024;14:47-74. doi: 10.2147/DNND.S452009
Bhatt S, Puli L, Patil CR. Role of reactive oxygen species in the progression of Alzheimer's disease. Drug Discov Today. 2021;26(3):794-803. doi: 10.1016/j.drudis.2020.12.004
Sanfeliu C, Bartra C, Suñol C, Rodríguez-Farré E. New insights in animal models of neurotoxicity-induced neurodegeneration. Front Neurosci. 2024;17:1248727. doi: 10.3389/fnins.2023.1248727
Singh M, Agarwal V, Pancham P, et al. A comprehensive review and androgen deprivation therapy and its impact on Alzheimer's disease risk in older men with prostate cancer. Degener Neurol Neuromuscul Dis. 2024;14:33-46. doi: 10.2147/DNND.S445130
Morshed AKMH, Paul S, Hossain A, et al. Baicalein as promising anticancer agent: A comprehensive analysis on molecular mechanisms and therapeutic perspectives. Cancers (Basel). 2023;15(7):2128. doi: 10.3390/cancers15072128
Siddiqui N, Talib M, Tripathi PN, Kumar A, Sharma A. Therapeutic potential of baicalein against neurodegenerative diseases: an updated review. Health Sci Rev. 2024;11:100172. doi: 10.1016/j.hsr.2024.100172
Yatoo MI, Gopalakrishnan A, Saxena A, et al. Anti-Inflammatory drugs and herbs with special emphasis on herbal medicines for countering inflammatory diseases and disorders - a review. Recent Pat Inflamm Allergy Drug Discov. 2018;12(1):39-58. doi: 10.2174/1872213X12666180115153635
Meshram MA, Bhise UO, Makhal PN, Kaki VR. Synthetically-tailored and nature-derived dual COX-2/5-LOX inhibitors: Structural aspects and SAR. Eur J Med Chem. 2021;225:113804. doi: 10.1016/j.ejmech.2021.113804
Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem. 2015;30(1):11-26. doi: 10.1007/s12291-014-0446-0
Chaudhary P, Janmeda P, Docea AO, et al. Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Front Chem. 2023;11:1158198. doi: 10.3389/fchem.2023.1158198
Shrivastava SK, Avhad AN, Bhardwaj B, et al. Drug reposition-based design, synthesis, and biological evaluation of dual inhibitors of acetylcholinesterase and β-secretase for treatment of Alzheimer's disease. J Mol Struct. 2022;1262:132979. doi: 10.1016/j.molstruc.2022.132979
El-Shorbagi AN, Chaudhary S, Chaudhary A, et al. Marine antineoplastic templates: clinical trials (I-III) and motifs carried via antibodies to target specific cancerous tissues. Biomed Pharmacol J. 2022;15(2):579-603. doi: 10.13005/bpj/2398
Noori T, Dehpour AR, Sureda A, Sobarzo-Sanchez E, Shirooie S. Role of natural products for the treatment of Alzheimer's disease. Eur J Pharmacol. 2021;898:173974. doi: 10.1016/j.ejphar.2021.173974
Aran KR, Gupta GD, Singh S. Lansoprazole induces hippocampal cell apoptosis and impairs learning and memory functions via activation of tau phosphorylation and Aβ (1–42) pathway in adult rats. Toxicol Environ Health Sci. 2024;22:1-6.
Zhou L, Tan S, Shan YL, et al. Baicalein improves behavioral dysfunction induced by Alzheimer's disease in rats. Neuropsychiatr Dis Treat. 2016;12:3145-3152. doi: 10.2147/NDT.S117469
Bashir S, Aiman A, Shahid M, et al. Amyloid-induced neurodegeneration: a comprehensive review through aggregomics perception of proteins in health and pathology. Ageing Res Rev. 2024;96:102276. doi: 10.1016/j.arr.2024.102276
Hampel H, Mesulam MM, Cuello AC, et al. Revisiting the Cholinergic Hypothesis in Alzheimer's Disease: Emerging Evidence from Translational and Clinical Research. J Prev Alzheimers Dis. 2019;6(1):2-15. doi: 10.14283/jpad.2018.43
Thomas R, Ambookan PV, Jose J, Unnikrishnan UG. The accuracy of anthropometric measurements of general and central obesity for the prediction of impaired glucose tolerance among the adult population of South India. J Family Med Prim Care. 2020;9(7):3416-3420. doi: 10.4103/jfmpc.jfmpc_269_20
Sparling JE, Baker SL, Bielajew C. Effects of combined pre- and post-natal enrichment on anxiety-like, social, and cognitive behaviours in juvenile and adult rat offspring. Behav Brain Res. 2018;353:40-50. doi: 10.1016/j.bbr.2018.06.033
Arora S, Dharavath RN, Bansal Y, et al. Neurobehavioral alterations in a mouse model of chronic partial sleep deprivation. Metab Brain Dis. 2021;36(6):1315-1330. doi: 10.1007/s11011-021-00693-9
Hazim AI, Ramanathan S, Parthasarathy S, et al. Anxiolytic-like effects of mitragynine in the open-field and elevated plus-maze tests in rats. J Physiol Sci. 2014;64(3):161-169. doi: 10.1007/s12576-014-0304-0
Xiao S, Yan Y, Zhao J, et al. Increased microneedle-mediated transdermal delivery of tetramethylpyrazine to the brain, combined with borneol and iontophoresis, for MCAO prevention. Int J Pharm. 2020;575:118962. doi: 10.1016/j.ijpharm.2019.118962
Tung BT, Hai NT, Thu DK. Antioxidant and acetylcholinesterase inhibitory activities in vitro of different fractions of Huperzia squarrosa (Forst.) Trevis extract and attenuation of scopolamine-induced cognitive impairment in mice. J Ethnopharmacol. 2017;198:24-32. doi: 10.1016/j.jep.2016.12.037
Ademowo OS, Dias HKI, Milic I, et al. Phospholipid oxidation and carotenoid supplementation in Alzheimer's disease patients. Free Radic Biol Med. 2017;108:77-85. doi: 10.1016/j.freeradbiomed.2017.03.008
Ayub M, Javed M, Latif F, Ambreen F, Sabir K. Tissue Specific Changes in the Antioxidant Enzyme Activity of Manganese Exposed Labeo rohita. Punjab Univ J Zool. 2019;34(2):127-132.
Parihar MS, Javeri T, Hemnani T, Dubey AK, Prakash P. Responses of superoxide dismutase, glutathione peroxidase and reduced glutathione antioxidant defenses in gills of the freshwater catfish (Heteropneustes fossilis) to short-term elevated temperature. J Therm Biol. 1997;22(2):151-156.
Marklund SL. Superoxide dismutase isoenzymes in tissues and plasma from New Zealand black mice, nude mice and normal BALB/c mice. Mutat Res. 1985;148(1-2):129-134. doi: 10.1016/0027-5107(85)90216-7
Agarwal M, Singh M, Hussain J. Assessment of groundwater quality with special emphasis on nitrate contamination in parts of Gautam Budh Nagar district, Uttar Pradesh, India. Acta Geochim. 2019;38:703-717.
Albekairi TH, Kamra A, Bhardwaj S, et al. Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington's Disease. Biomedicines. 2022;10(11):2866. doi: 10.3390/biomedicines10112866
Giri A, Mehan S, Khan Z, et al. Melatonin-mediated IGF-1/GLP-1 activation in experimental OCD rats: Evidence from CSF, blood plasma, brain and in-silico investigations. Biochem Pharmacol. 2023;217:115831. doi: 10.1016/j.bcp.2023.115831
Prajapati A, Mehan S, Khan Z, et al. Purmorphamine, a Smo-Shh/Gli Activator, Promotes Sonic Hedgehog-Mediated Neurogenesis and Restores Behavioural and Neurochemical Deficits in Experimental Model of Multiple Sclerosis. Neurochem Res. 2024;49(6):1556-1576. doi: 10.1007/s11064-023-04082-9
Goel F, Kumar D, Sharma A. Impact of corticoid receptors on Alzheimer’s disease: a neuroendocrine perspective. Inflammopharmacology. 2025;33(5):1-6. doi: 10.1007/s10787-025-01734-w
Perluigi M, Di Domenico F, Butterfield DA. Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer disease. Physiol Rev. 2024;104(1):103-197. doi: 10.1152/physrev.00030.2022
Li Y, Song K, Zhang H, et al. Anti-inflammatory and immunomodulatory effects of baicalin in cerebrovascular and neurological disorders. Brain Res Bull. 2020;164:314-324. doi: 10.1016/j.brainresbull.2020.08.016
Aran KR, Gupta GD, Singh S. Lansoprazole induces hippocampal cell apoptosis and impairs learning and memory functions via activation of tau phosphorylation and Aβ (1–42) pathway in adult rats. Toxicol Environ Health Sci. 2024:1-6.
Behera S, Das A, Shree J, et al. The visual field-testing maze and vision maze: Feasible techniques to evaluate visual field loss in animals. J Pharmacol Toxicol Methods. 2024;126:107495. doi: 10.1016/j.vascn.2024.107495
Yıldız MO, Çelik H, Caglayan C, et al. Neuroprotective effects of carvacrol against cadmium-induced neurotoxicity in rats: role of oxidative stress, inflammation and apoptosis. Metab Brain Dis. 2022;37(4):1259-1269. doi: 10.1007/s11011-022-00945-2
Mehrzadi S, Sheibani M, Koosha F, et al. Protective and therapeutic potential of melatonin against intestinal diseases: updated review of current data based on molecular mechanisms. Expert Rev Gastroenterol Hepatol. 2023;17(10):1011-1029. doi: 10.1080/17474124.2023.2267439
Choi GY, Kim HB, Cho JM, et al. Umbelliferone ameliorates memory impairment and enhances hippocampal synaptic plasticity in scopolamine-induced rat model. Nutrients. 2023;15(10):2351. doi: 10.3390/nu15102351
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