Year 2025,
Volume: 13 Issue: 2, 29 - 37, 29.08.2025
Mehtap Savran
,
Nursel Hasseyid
,
Orhan İmeci
,
Özlem Özmen
References
-
Abu-Baih, R. H., Ibrahim, M. F. G., Elhamadany, E. Y., & Abu-Baih, D. H. (2024). Irbesartan mitigates the impact of cyclophosphamide-induced acute neurotoxicity in rats: Shedding highlights on NLRP3 inflammasome/CASP-1 pathway-driven immunomodulation. International Immunopharmacology, 135. https://doi.org/10.1016/j.intimp.2024.112336
-
Al-Ghraiybah, N. F., Wang, J., Alkhalifa, A. E., Roberts, A. B., Raj, R., Yang, E., & Kaddoumi, A. (2022). Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease. International Journal of Molecular Sciences, 23(18). https://doi.org/10.3390/IJMS231810572
-
Al-Kuraishy, H., Al-Gareeb, A., & Al-Nami, M. (2020). Irbesartan Attenuates Gentamicin-induced Nephrotoxicity in Rats through Modulation of Oxidative Stress and Endogenous Antioxidant Capacity. International Journal of Preventive Medicine, 11(1). https://doi.org/10.4103/IJPVM.IJPVM_567_18
-
Aslankoc, R., Savran, M., Doğuç, D. K., Sevimli, M., Tekin, H., & Kaynak, M. (2022). Ameliorating effects of ramelteon on oxidative stress, inflammation, apoptosis, and autophagy markers in methotrexate-induced cerebral toxicity. Iranian Journal of Basic Medical Sciences, 25(10), 1183–1189. https://doi.org/10.22038/IJBMS.2022.62955.13913
-
Blanchet, M., Sheppard, R., Racine, N., Ducharme, A., Curnier, D., Tardif, J. C., Sirois, P., Lamoureux, M. C., De Champlain, J., & White, M. (2005). Effects of angiotensin-converting enzyme inhibitor plus irbesartan on maximal and submaximal exercise capacity and neurohumoral activation in patients with congestive heart failure. American Heart Journal, 149(5), 938.e1-938.e7. https://doi.org/10.1016/j.ahj.2004.11.011
-
Cao, C., Gao, T., Cheng, M., Xi, F., Zhao, C., & Yu, W. (2017). Mild hypothermia ameliorates muscle wasting in septic rats associated with hypothalamic AMPK-induced autophagy and neuropeptides. Biochemical and Biophysical Research Communications, 490(3), 882–888. https://doi.org/10.1016/J.BBRC.2017.06.135
-
Ceriello, A., Assaloni, R., Da Ros, R., Maier, A., Piconi, L., Quagliaro, L., Esposito, K., & Giugliano, D. (2005). Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients. Circulation, 111(19), 2518–2524. https://doi.org/10.1161/01.CIR.0000165070.46111.9F
-
Dai, W., Shi, J., & Ge, J. (1988). Effects of Irbesartan on the plasma concentrations of lysophosphatidic acid, endothelin-1,and serum concentration of nitric oxcide in the patients with acute cerebral infarction. Journal of Clinical Neurology. http://dx.doi.org/
-
Dogan Unlu, M., Asci, S., Asci, H., Agirca Tasan, S., Ozmen, O., Taner, R., & Demirci, S. (2024). Lercanidipine ameliorated doxorubicin-induced neuroinflammation and maintained the expressions of choline acetyltransferase via enhancing the levels of PI3K/AKT/HIF1-α expressions. Molecular Biology Reports, 51(1). https://doi.org/10.1007/S11033-023-09024-W
-
Gouveia, F., Fonseca, C., Silva, A., Camins, A., Teresa Cruz, M., Ettcheto, M., & Fortuna, A. (2024). Intranasal irbesartan reverts cognitive decline and activates the PI3K/AKT pathway in an LPS-induced neuroinflammation mice model. International Immunopharmacology, 128. https://doi.org/10.1016/j.intimp.2023.111471
-
Gouveia, F., Pérez, M. C., Bicker, J., Silva, A., Santos, A. E., Pereira, C. F., Camins, A., Falcão, A., Cruz, T., Ettcheto, M., & Fortuna, A. (2025). Protective effects of irbesartan against neurodegeneration in APP/PS1 mice: Unraveling its triple anti-apoptotic, anti-inflammatory and anti-oxidant action. Biomedicine and Pharmacotherapy, 188. https://doi.org/10.1016/j.biopha.2025.118167
-
Hachiya, K., Masuya, M., Kuroda, N., Yoneda, M., Tsuboi, J., Nagaharu, K., Nishimura, K., Shiotani, T., Ohishi, K., Tawara, I., & Katayama, N. (2021). Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway. Scientific Reports, 11(1). https://doi.org/10.1038/S41598-021-99412-8
-
Hao, S., He, Q., Yuan, Y., & Mu, Q. (2024). The protective effects of Irbesartan in cognitive impairment in hypertension. Aging, 16(6), 5066–5076. https://doi.org/10.18632/AGING.205589,
-
İlhan, İ., Aşçi, H., Hasseyid, N., Doğan, H. K., Ağirca, Ş., Altintaş, M., & Tepebasi, M. Y. (2022). Irbesartan decreased mitochondrial stress related apoptosis in cisplatin induced acute kidney injury via regulating BCL-2/BAX signaling. Molecular Biology Reports, 49(7), 6125–6133. https://doi.org/10.1007/S11033-022-07403-3
-
Imeci, O., Asci, H., Asci, S., Sevuk, M. A., Sarikaya, H. S., & Ozmen, O. (2025). Dapagliflozin mitigates lipopolysaccharide-induced neuroinflammation through potential involvement of the IL-17A/GSK3β signaling pathway and modulation of inflammatory cytokines. European Journal of Pharmacology, 1003. https://doi.org/10.1016/j.ejphar.2025.177913
-
Issa, N. (2022). Making a Case for the Anti-inflammatory Effects of ACE Inhibitors and Angiotensin II Receptor Blockers: Evidence From Randomized Controlled Trials. Mayo Clinic Proceedings, 97(10), 1766–1768. https://doi.org/10.1016/J.MAYOCP.2022.08.009
-
Nava Catorce, M., & Gevorkian, G. (2016). LPS-induced Murine Neuroinflammation Model: Main Features and Suitability for Pre-clinical Assessment of Nutraceuticals. Current Neuropharmacology, 14(2), 155–164. https://doi.org/10.2174/1570159X14666151204122017
-
Özcan, M. S., Aşcı, H., Karabacak, P., Özden, E. S., İmeci, O. B., & Özmen, Ö. (2025). Remifentanil Ameliorates Lipopolysaccharide-Induced Neuroinflammation by Regulating the Phosphatidylinositol 3-Kinase/Serine-Threonine Protein Kinase/Hypoxia-Inducible Factor 1 Alpha Pathway. Pharmacology Research & Perspectives, 13(1). https://doi.org/10.1002/PRP2.70071
-
Parving, H.-H., Lehnert, H., Bröchner-Mortensen, J., Gomis, R., Andersen, S., & Arner, P. (2001). The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. The New England Journal of Medicine, 345(12), 870–878. https://doi.org/10.1056/NEJMOA011489
-
Polidori, C., Ciccocioppo, R., Nisato, D., Cazaubon, C., & Massi, M. (1998). Evaluation of the ability of irbesartan to cross the blood-brain barrier following acute intragastric treatment. European Journal of Pharmacology, 352(1), 15–21. https://doi.org/10.1016/S0014-2999(98)00329-X
-
Rao, G. N., Jupudi, S., & Justin, A. (2024). A Review on Neuroinflammatory Pathway Mediating Through Ang-II/AT1 Receptors and a Novel Approach for the Treatment of Cerebral Ischemia in Combination with ARB’s and Ceftriaxone. Annals of Neurosciences, 31(1), 53–62. https://doi.org/10.1177/09727531231182554
-
Rossing, K., Schjoedt, K. J., Jensen, B. R., Boomsma, F., & Parving, H. H. (2005). Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria. Kidney International, 68(3), 1190–1198. https://doi.org/10.1111/J.1523-1755.2005.00511.X
-
Salmenkari, H., Pasanen, L., Linden, J., Korpela, R., & Vapaatalo, H. (2018). Beneficial anti-inflammatory effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker in the treatment of dextran sulfate sodium-induced colitis in mice. Journal of Physiology and Pharmacology : An Official Journal of the Polish Physiological Society, 69(4). https://doi.org/10.26402/JPP.2018.4.07
-
Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., Challis, C., Schretter, C. E., Rocha, S., Gradinaru, V., Chesselet, M. F., Keshavarzian, A., Shannon, K. M., Krajmalnik-Brown, R., Wittung-Stafshede, P., Knight, R., & Mazmanian, S. K. (2016). Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell, 167(6), 1469-1480.e12. https://doi.org/10.1016/J.CELL.2016.11.018
-
Taguchi, I., Toyoda, S., Takano, K., Arikawa, T., Kikuchi, M., Ogawa, M., Abe, S., Node, K., & Inoue, T. (2013). Irbesartan, an angiotensin receptor blocker, exhibits metabolic, anti-inflammatory and antioxidative effects in patients with high-risk hypertension. Hypertension Research : Official Journal of the Japanese Society of Hypertension, 36(7), 608–613. https://doi.org/10.1038/HR.2013.3
-
Tran, S., Kuruppu, S., & Rajapakse, N. W. (2022). Chronic Renin-Angiotensin System Activation Induced Neuroinflammation: Common Mechanisms Underlying Hypertension and Dementia? Journal of Alzheimer’s Disease, 85(3), 943–955. https://doi.org/10.3233/JAD-215231,
-
Tsukuda, K., Mogi, M., Iwanami, J., Min, L. J., Jing, F., Oshima, K., & Horiuchi, M. (2011). Irbesartan attenuates ischemic brain damage by inhibition of MCP-1/CCR2 signaling pathway beyond AT₁ receptor blockade. Biochemical and Biophysical Research Communications, 409(2), 275–279. https://doi.org/10.1016/J.BBRC.2011.04.142
-
Ünlü, M. D., Aşçı, S., İmeci, O., Milletsever, A., Özmen, Ö., Sezer, S., & Demirci, S. (2024). A novel insight into the neuroprotective effects of cannabidiol: maintained apelin/dopamine synthesis, NRF2 signaling, and AKT/CREB/BDNF gene expressions. Acta Neurobiologiae Experimentalis, 84(1), 98–110. https://doi.org/10.55782/ANE-2024-2546
-
Yang, L., Zhou, R., Tong, Y., Chen, P., Shen, Y., Miao, S., & Liu, X. (2020). Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation. Neurobiology of Disease, 140. https://doi.org/10.1016/J.NBD.2020.104814
-
Yang, Q., Yu, J., Qin, H., Liu, L., Di, C., Zhuang, Q., & Yin, H. (2021a). Irbesartan suppresses lipopolysaccharide (LPS)-induced blood–brain barrier (BBB) dysfunction by inhibiting the activation of MLCK/MLC. International Immunopharmacology, 98, 107834. https://doi.org/10.1016/J.INTIMP.2021.107834
-
Yang, Q., Yu, J., Qin, H., Liu, L., Di, C., Zhuang, Q., & Yin, H. (2021b). Irbesartan suppresses lipopolysaccharide (LPS)-induced blood–brain barrier (BBB) dysfunction by inhibiting the activation of MLCK/MLC. International Immunopharmacology, 98. https://doi.org/10.1016/j.intimp.2021.107834
-
Yousif, N. G., Hadi, N. R., Al-Amran, F., & Zigam, Q. A. (2018). Cardioprotective effects of irbesartan in polymicrobial sepsis : The role of the p38MAPK/NF-κB signaling pathway. Herz, 43(2), 140–145. https://doi.org/10.1007/S00059-017-4537-6
-
Zhang, J., Zheng, Y., Luo, Y., Du, Y., Zhang, X., & Fu, J. (2019). Curcumin inhibits LPS-induced neuroinflammation by promoting microglial M2 polarization via TREM2/ TLR4/ NF-κB pathways in BV2 cells. Molecular Immunology, 116, 29–37. https://doi.org/10.1016/J.MOLIMM.2019.09.020
Histological and Immunohistochemical Insights into the Neuroprotective Effects of Ibresartan on Lipopolysaccharide-Induced Neuroinflammation
Year 2025,
Volume: 13 Issue: 2, 29 - 37, 29.08.2025
Mehtap Savran
,
Nursel Hasseyid
,
Orhan İmeci
,
Özlem Özmen
Abstract
Neuroinflammation is a key contributor to the development of various neurological and psychiatric disorders. Irbesartan (IRB), a selective angiotensin receptor blocker, has demonstrated protective properties in multiple organ systems. This study investigates the potential neuroprotective effect of IRB against lipopolysaccharide (LPS)-induced neuroinflammation. Twenty-four male Wistar Albino rats were randomly assigned into three groups: control, LPS-treated (5 mg/kg), and LPS+IRB-treated (IRB 3 mg/kg). All drugs were given intraperitoneally. One hour after the LPS injection, the IRB group received the treatment. Six hours post-LPS administration, animals were sacrificed, and tissues were gathered for hematoxylin-eosin and immunostaining assessments. Caspase-3 and tumor necrosis factor-alpha levels were analyzed. LPS exposure led to notable pathological changes, including vascular congestion, edema, infiltration of neutrophils, micro hemorrhages, and neuronal degeneration in the examined brain regions. Immunohistochemistry revealed a marked elevation in apoptotic and inflammatory marker expression levels in the LPS group. Treatment with IRB significantly reduced both the histopathological damage and the expression of these inflammatory and apoptotic markers. IRB alleviated the detrimental effects of LPS-induced neuroinflammation in the rat brain, supporting its potential as a neuroprotective agent. Further studies are required to determine its efficacy across varying dosages and administration protocols.
Ethical Statement
All animal experiments were conducted by institutional ethical standards and were reviewed and approved by the relevant ethics committee (SDÜ-HADYEK-17.02.2022/02/27).
Supporting Institution
Suleyman Demirel University Scientific Research Projects Coordination Unit [TSG-2024-9515].
Thanks
We thank to the Suleyman Demirel University Scientific Research Projects Coordination Unit for funding this research.
References
-
Abu-Baih, R. H., Ibrahim, M. F. G., Elhamadany, E. Y., & Abu-Baih, D. H. (2024). Irbesartan mitigates the impact of cyclophosphamide-induced acute neurotoxicity in rats: Shedding highlights on NLRP3 inflammasome/CASP-1 pathway-driven immunomodulation. International Immunopharmacology, 135. https://doi.org/10.1016/j.intimp.2024.112336
-
Al-Ghraiybah, N. F., Wang, J., Alkhalifa, A. E., Roberts, A. B., Raj, R., Yang, E., & Kaddoumi, A. (2022). Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease. International Journal of Molecular Sciences, 23(18). https://doi.org/10.3390/IJMS231810572
-
Al-Kuraishy, H., Al-Gareeb, A., & Al-Nami, M. (2020). Irbesartan Attenuates Gentamicin-induced Nephrotoxicity in Rats through Modulation of Oxidative Stress and Endogenous Antioxidant Capacity. International Journal of Preventive Medicine, 11(1). https://doi.org/10.4103/IJPVM.IJPVM_567_18
-
Aslankoc, R., Savran, M., Doğuç, D. K., Sevimli, M., Tekin, H., & Kaynak, M. (2022). Ameliorating effects of ramelteon on oxidative stress, inflammation, apoptosis, and autophagy markers in methotrexate-induced cerebral toxicity. Iranian Journal of Basic Medical Sciences, 25(10), 1183–1189. https://doi.org/10.22038/IJBMS.2022.62955.13913
-
Blanchet, M., Sheppard, R., Racine, N., Ducharme, A., Curnier, D., Tardif, J. C., Sirois, P., Lamoureux, M. C., De Champlain, J., & White, M. (2005). Effects of angiotensin-converting enzyme inhibitor plus irbesartan on maximal and submaximal exercise capacity and neurohumoral activation in patients with congestive heart failure. American Heart Journal, 149(5), 938.e1-938.e7. https://doi.org/10.1016/j.ahj.2004.11.011
-
Cao, C., Gao, T., Cheng, M., Xi, F., Zhao, C., & Yu, W. (2017). Mild hypothermia ameliorates muscle wasting in septic rats associated with hypothalamic AMPK-induced autophagy and neuropeptides. Biochemical and Biophysical Research Communications, 490(3), 882–888. https://doi.org/10.1016/J.BBRC.2017.06.135
-
Ceriello, A., Assaloni, R., Da Ros, R., Maier, A., Piconi, L., Quagliaro, L., Esposito, K., & Giugliano, D. (2005). Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients. Circulation, 111(19), 2518–2524. https://doi.org/10.1161/01.CIR.0000165070.46111.9F
-
Dai, W., Shi, J., & Ge, J. (1988). Effects of Irbesartan on the plasma concentrations of lysophosphatidic acid, endothelin-1,and serum concentration of nitric oxcide in the patients with acute cerebral infarction. Journal of Clinical Neurology. http://dx.doi.org/
-
Dogan Unlu, M., Asci, S., Asci, H., Agirca Tasan, S., Ozmen, O., Taner, R., & Demirci, S. (2024). Lercanidipine ameliorated doxorubicin-induced neuroinflammation and maintained the expressions of choline acetyltransferase via enhancing the levels of PI3K/AKT/HIF1-α expressions. Molecular Biology Reports, 51(1). https://doi.org/10.1007/S11033-023-09024-W
-
Gouveia, F., Fonseca, C., Silva, A., Camins, A., Teresa Cruz, M., Ettcheto, M., & Fortuna, A. (2024). Intranasal irbesartan reverts cognitive decline and activates the PI3K/AKT pathway in an LPS-induced neuroinflammation mice model. International Immunopharmacology, 128. https://doi.org/10.1016/j.intimp.2023.111471
-
Gouveia, F., Pérez, M. C., Bicker, J., Silva, A., Santos, A. E., Pereira, C. F., Camins, A., Falcão, A., Cruz, T., Ettcheto, M., & Fortuna, A. (2025). Protective effects of irbesartan against neurodegeneration in APP/PS1 mice: Unraveling its triple anti-apoptotic, anti-inflammatory and anti-oxidant action. Biomedicine and Pharmacotherapy, 188. https://doi.org/10.1016/j.biopha.2025.118167
-
Hachiya, K., Masuya, M., Kuroda, N., Yoneda, M., Tsuboi, J., Nagaharu, K., Nishimura, K., Shiotani, T., Ohishi, K., Tawara, I., & Katayama, N. (2021). Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway. Scientific Reports, 11(1). https://doi.org/10.1038/S41598-021-99412-8
-
Hao, S., He, Q., Yuan, Y., & Mu, Q. (2024). The protective effects of Irbesartan in cognitive impairment in hypertension. Aging, 16(6), 5066–5076. https://doi.org/10.18632/AGING.205589,
-
İlhan, İ., Aşçi, H., Hasseyid, N., Doğan, H. K., Ağirca, Ş., Altintaş, M., & Tepebasi, M. Y. (2022). Irbesartan decreased mitochondrial stress related apoptosis in cisplatin induced acute kidney injury via regulating BCL-2/BAX signaling. Molecular Biology Reports, 49(7), 6125–6133. https://doi.org/10.1007/S11033-022-07403-3
-
Imeci, O., Asci, H., Asci, S., Sevuk, M. A., Sarikaya, H. S., & Ozmen, O. (2025). Dapagliflozin mitigates lipopolysaccharide-induced neuroinflammation through potential involvement of the IL-17A/GSK3β signaling pathway and modulation of inflammatory cytokines. European Journal of Pharmacology, 1003. https://doi.org/10.1016/j.ejphar.2025.177913
-
Issa, N. (2022). Making a Case for the Anti-inflammatory Effects of ACE Inhibitors and Angiotensin II Receptor Blockers: Evidence From Randomized Controlled Trials. Mayo Clinic Proceedings, 97(10), 1766–1768. https://doi.org/10.1016/J.MAYOCP.2022.08.009
-
Nava Catorce, M., & Gevorkian, G. (2016). LPS-induced Murine Neuroinflammation Model: Main Features and Suitability for Pre-clinical Assessment of Nutraceuticals. Current Neuropharmacology, 14(2), 155–164. https://doi.org/10.2174/1570159X14666151204122017
-
Özcan, M. S., Aşcı, H., Karabacak, P., Özden, E. S., İmeci, O. B., & Özmen, Ö. (2025). Remifentanil Ameliorates Lipopolysaccharide-Induced Neuroinflammation by Regulating the Phosphatidylinositol 3-Kinase/Serine-Threonine Protein Kinase/Hypoxia-Inducible Factor 1 Alpha Pathway. Pharmacology Research & Perspectives, 13(1). https://doi.org/10.1002/PRP2.70071
-
Parving, H.-H., Lehnert, H., Bröchner-Mortensen, J., Gomis, R., Andersen, S., & Arner, P. (2001). The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. The New England Journal of Medicine, 345(12), 870–878. https://doi.org/10.1056/NEJMOA011489
-
Polidori, C., Ciccocioppo, R., Nisato, D., Cazaubon, C., & Massi, M. (1998). Evaluation of the ability of irbesartan to cross the blood-brain barrier following acute intragastric treatment. European Journal of Pharmacology, 352(1), 15–21. https://doi.org/10.1016/S0014-2999(98)00329-X
-
Rao, G. N., Jupudi, S., & Justin, A. (2024). A Review on Neuroinflammatory Pathway Mediating Through Ang-II/AT1 Receptors and a Novel Approach for the Treatment of Cerebral Ischemia in Combination with ARB’s and Ceftriaxone. Annals of Neurosciences, 31(1), 53–62. https://doi.org/10.1177/09727531231182554
-
Rossing, K., Schjoedt, K. J., Jensen, B. R., Boomsma, F., & Parving, H. H. (2005). Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria. Kidney International, 68(3), 1190–1198. https://doi.org/10.1111/J.1523-1755.2005.00511.X
-
Salmenkari, H., Pasanen, L., Linden, J., Korpela, R., & Vapaatalo, H. (2018). Beneficial anti-inflammatory effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker in the treatment of dextran sulfate sodium-induced colitis in mice. Journal of Physiology and Pharmacology : An Official Journal of the Polish Physiological Society, 69(4). https://doi.org/10.26402/JPP.2018.4.07
-
Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., Challis, C., Schretter, C. E., Rocha, S., Gradinaru, V., Chesselet, M. F., Keshavarzian, A., Shannon, K. M., Krajmalnik-Brown, R., Wittung-Stafshede, P., Knight, R., & Mazmanian, S. K. (2016). Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell, 167(6), 1469-1480.e12. https://doi.org/10.1016/J.CELL.2016.11.018
-
Taguchi, I., Toyoda, S., Takano, K., Arikawa, T., Kikuchi, M., Ogawa, M., Abe, S., Node, K., & Inoue, T. (2013). Irbesartan, an angiotensin receptor blocker, exhibits metabolic, anti-inflammatory and antioxidative effects in patients with high-risk hypertension. Hypertension Research : Official Journal of the Japanese Society of Hypertension, 36(7), 608–613. https://doi.org/10.1038/HR.2013.3
-
Tran, S., Kuruppu, S., & Rajapakse, N. W. (2022). Chronic Renin-Angiotensin System Activation Induced Neuroinflammation: Common Mechanisms Underlying Hypertension and Dementia? Journal of Alzheimer’s Disease, 85(3), 943–955. https://doi.org/10.3233/JAD-215231,
-
Tsukuda, K., Mogi, M., Iwanami, J., Min, L. J., Jing, F., Oshima, K., & Horiuchi, M. (2011). Irbesartan attenuates ischemic brain damage by inhibition of MCP-1/CCR2 signaling pathway beyond AT₁ receptor blockade. Biochemical and Biophysical Research Communications, 409(2), 275–279. https://doi.org/10.1016/J.BBRC.2011.04.142
-
Ünlü, M. D., Aşçı, S., İmeci, O., Milletsever, A., Özmen, Ö., Sezer, S., & Demirci, S. (2024). A novel insight into the neuroprotective effects of cannabidiol: maintained apelin/dopamine synthesis, NRF2 signaling, and AKT/CREB/BDNF gene expressions. Acta Neurobiologiae Experimentalis, 84(1), 98–110. https://doi.org/10.55782/ANE-2024-2546
-
Yang, L., Zhou, R., Tong, Y., Chen, P., Shen, Y., Miao, S., & Liu, X. (2020). Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation. Neurobiology of Disease, 140. https://doi.org/10.1016/J.NBD.2020.104814
-
Yang, Q., Yu, J., Qin, H., Liu, L., Di, C., Zhuang, Q., & Yin, H. (2021a). Irbesartan suppresses lipopolysaccharide (LPS)-induced blood–brain barrier (BBB) dysfunction by inhibiting the activation of MLCK/MLC. International Immunopharmacology, 98, 107834. https://doi.org/10.1016/J.INTIMP.2021.107834
-
Yang, Q., Yu, J., Qin, H., Liu, L., Di, C., Zhuang, Q., & Yin, H. (2021b). Irbesartan suppresses lipopolysaccharide (LPS)-induced blood–brain barrier (BBB) dysfunction by inhibiting the activation of MLCK/MLC. International Immunopharmacology, 98. https://doi.org/10.1016/j.intimp.2021.107834
-
Yousif, N. G., Hadi, N. R., Al-Amran, F., & Zigam, Q. A. (2018). Cardioprotective effects of irbesartan in polymicrobial sepsis : The role of the p38MAPK/NF-κB signaling pathway. Herz, 43(2), 140–145. https://doi.org/10.1007/S00059-017-4537-6
-
Zhang, J., Zheng, Y., Luo, Y., Du, Y., Zhang, X., & Fu, J. (2019). Curcumin inhibits LPS-induced neuroinflammation by promoting microglial M2 polarization via TREM2/ TLR4/ NF-κB pathways in BV2 cells. Molecular Immunology, 116, 29–37. https://doi.org/10.1016/J.MOLIMM.2019.09.020