Volume 29, Issue 3 (September 2025)                   Physiol Pharmacol 2025, 29(3): 232-239 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Salari S, Azizi M, Alihosseini T, Bagheri M. Neuroprotective effect of silibinin linked with attenuated Interleukin-6 and TNFα in an Aβ1-40 Induced Alzheimer’s rat model. Physiol Pharmacol 2025; 29 (3) : 1
URL: http://ppj.phypha.ir/article-1-2337-en.html
Abstract:   (1566 Views)

Introduction: The mechanisms behind Alzheimer’s disease (AD) remain largely unclear. Reactive oxygen species and inflammatory cytokines contribute to inflammation and synaptic dysfunction in AD. This study investigates whether silibinin’s neuroprotective properties act through regulating oxidative stress and inflammation.
Methods: Forty-eight Wistar rats (230±20g) were divided into four groups. The control group comprised healthy animals, while the lesion group received amyloid beta (Aβ 1-40 ). The vehicle group received silibinin solvent post-Aβ1-40 injection. Treatment groups received silibinin (50, 100, and 200 mg/kg) after Aβ1-40 injection. Following a passive avoidance behavior test, biochemical analysis of superoxide dismutase (SOD), malondialdehyde, Tumor necrosis factor α (TNF -α) and interleukin-6 (IL-6) was conducted.
Results: Administration of 100 mg/kg silibinin significantly reduced serum IL-6 levels compared to the lesion group (P=0.005). All silibinin doses significantly decreased TNF-α levels (P≤0.001). Serum superoxide dismutase (SOD) levels increased significantly in animals treated with 100 and 200 mg/kg silibinin compared to the lesion group (P=0.002, P=0.03). Step-through latency improved in silibinin-treated animals (100 and 200 mg/kg) (P≤0.006).
Conclusion: These results suggest silibinin can enhance cognitive function and offer neuroprotection by inhibiting lipid peroxidation and reducing pro-inflammatory cytokines (TNF-α and IL-6) in AD rat models.

Article number: 1
Full-Text [PDF 756 kb]   (85 Downloads)    
Type of Manuscript: Short communication | Subject: Neurophysiology/Pharmacology

References
1. Ahmadi-Naji R, Heidarian E, Ghatreh-Samani K. Evaluation of the effects of the hydroalcoholic extract of Terminalia chebula fruits on diazinon-induced liver toxicity and oxidative stress in rats. Avicenna journal of phytomedicine 2017; 7: 454.
2. Alihosseini T, Azizi M, Abbasi N, Mohammadpour S, Bagheri M. Amelioration of amyloid beta (Abeta(1-40)) neurotoxicity by administration of silibinin; a behavioral and biochemical assessment. ranian Journal of Basic Medical Sciences 2023a; 26: 791-798.
3. Bagheri M, Joghataei M-T, Mohseni S, Roghani M. Genistein ameliorates learning and memory deficits in amyloid β (1-40) rat model of Alzheimer’s disease. Neurobiology of Learning and Memory 2011; 95: 270-276. [DOI:10.1016/j.nlm.2010.12.001]
4. Bagheri M, Roghani M, Joghataei M T, Mohseni S. Genistein inhibits aggregation of exogenous amyloid-beta(1)(-)(4)(0) and alleviates astrogliosis in the hippocampus of rats. Brain Reserch 2012; 1429: 145-154. [DOI:10.1016/j.brainres.2011.10.020]
5. Bai D, Jin G, Yin S, Zou D, Zhu Q, Yang Z, et al. Antioxidative and anti-apoptotic roles of silibinin in reversing learning and memory deficits in APP/PS1 mice. Neurochemical Research 2017; 42: 3439-3445. [DOI:10.1007/s11064-017-2389-3]
6. Bai D, Jin G, Zhang D, Zhao L, Wang M, Zhu Q, et al. Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice. The Journal of Physiological Sciences 2019; 69: 643-652. [DOI:10.1007/s12576-019-00682-9]
7. Brahmachari S, Fung Y K, Pahan K. Induction of glial fibrillary acidic protein expression in astrocytes by nitric oxide. The Journal of Neuroscience 2006; 26: 4930-4939. [DOI:10.1523/JNEUROSCI.5480-05.2006]
8. Calsolaro V, Edison P. Neuroinflammation in Alzheimer’s disease: Current evidence and future directions. Alzheimers Dement 2016; 12: 719-732. [DOI:10.1016/j.jalz.2016.02.010]
9. Cunnane S C, Plourde M, Pifferi F, Bégin M, Féart C, Barberger-Gateau P. Fish, docosahexaenoic acid and Alzheimer’s disease. Progress in Lipid Research 2009; 48: 239-256. [DOI:10.1016/j.plipres.2009.04.001]
10. Duan R, Hou J, Wang X, Huang Z, Cao H, Hu J, et al. Prevotella histicola transplantation ameliorates cognitive impairment and decreases oxidative stress in vascular dementia rats. Brain Sciences 2023; 13: 1136. [DOI:10.3390/brainsci13081136]
11. Geed M, Garabadu D, Ahmad A, Krishnamurthy S. Silibinin pretreatment attenuates biochemical and behavioral changes induced by intrastriatal MPP+ injection in rats. Pharmacology Biochemistry and Behavior 2014; 117: 92-103. [DOI:10.1016/j.pbb.2013.12.008]
12. Ghofrani S, Joghataei M T, Mohseni S, Baluchnejadmojarad T, Bagheri M, Khamse S, et al. Naringenin improves learning and memory in an Alzheimer’s disease rat model: Insights into the underlying mechanisms. European Journal of Pharmacology 2015; 764: 195-201. [DOI:10.1016/j.ejphar.2015.07.001]
13. Hadinia A, Aryanpour R, Mehdizadeh M, Mahmodi R, Mossavizadeh A, Delaviz H, et al. The effect of silybum marianum on GFAP and spatial memory in a mouse model of alzheimer’s disease. Journal of American Science 2010; 14: 65-75.
14. Hou Y-C, Liou K-T, Chern C-M, Wang Y-H, Liao J-F, Chang S, et al. Preventive effect of silymarin in cerebral ischemia-reperfusion-induced brain injury in rats possibly through impairing NF-κB and STAT-1 activation. Phytomedicine 2010; 17: 963-973. [DOI:10.1016/j.phymed.2010.03.012]
15. Jangra A, Kasbe P, Pandey S N, Dwivedi S, Gurjar S S, Kwatra M, et al. Hesperidin and silibinin ameliorate aluminum-induced neurotoxicity: modulation of antioxidants and inflammatory cytokines level in mice hippocampus. Biological Trace Element Research 2015; 168: 462-471. [DOI:10.1007/s12011-015-0375-7]
16. Javier Jimenez-Jimenez F, Alonso-Navarro H, Trinidad Herrero M, García-Martín E, AG Agúndez J. An update on the role of nitric oxide in the neurodegenerative processes of Parkinson’s disease. Current Medicinal Chemistry 2016; 23: 2666-2679. [DOI:10.2174/0929867323666160812151356]
17. Liu B, Yang P, Ye Y, Zhou Y, Li L, Tashiro S-I, et al. Role of ROS in the protective effect of silibinin on sodium nitroprusside-induced apoptosis in rat pheochromocytoma PC12 cells. Free Radical Research 2011; 45: 835-847. [DOI:10.3109/10715762.2011.580343]
18. Liu P, Cui L, Liu B, Liu W, Hayashi T, Mizuno K, et al. Silibinin ameliorates STZ-induced impairment of memory and learning by up- regulating insulin signaling pathway and attenuating apoptosis. Physiology & Behavior 2020; 213: 112689. [DOI:10.1016/j.physbeh.2019.112689]
19. Lu P, Mamiya T, Lu L L, Mouri A, Zou L, Nagai T, et al. Silibinin prevents amyloid beta peptide-induced memory impairment and oxidative stress in mice. The British Journal of Pharmacology 2009; 157: 1270-1277. [DOI:10.1111/j.1476-5381.2009.00295.x]
20. Mateen S, Tyagi A, Agarwal C, Singh R P, Agarwal R. Silibinin inhibits human nonsmall cell lung cancer cell growth through cell-cycle arrest by modulating expression and function of key cell-cycle regulators. Molecular Carcinogenesis 2010; 49: 247-258. [DOI:10.1002/mc.20595]
21. Meng D, Wang Y, Liu T. Protective effects of silibinin on LPS-induced inflammation in human periodontal ligament cells. Frontiers in Chemistry 2022; 10: 1019663. [DOI:10.3389/fchem.2022.1019663]
22. Mohammadzadeh E, Alipour F, Khallaghi B. Evaluation of spatial memory impairment after intracerebroventricular streptozocin injection in adult rats. The Neuroscience Journal of Shefaye Khatam 2014; 2: 40-45. [DOI:10.18869/acadpub.shefa.2.1.40]
23. Park J, Kwon O S, Cho S Y, Paick J-S, Kim S W. Chronic administration of atorvastatin could partially ameliorate erectile function in streptozotocin-induced diabetic rats. PLoS One 2017; 12: e0172751. [DOI:10.1371/journal.pone.0172751]
24. Purdy P, Ericsson S, Dodson R, Sternes K, Garner D. Effects of the flavonoids, silibinin and catechin, on the motility of extended cooled caprine sperm. Small Ruminant Research 2004; 55: 239-243. [DOI:10.1016/j.smallrumres.2004.02.005]
25. Schmitt-Schillig S, Schaffer S, Weber C, Eckert G, Muller W . Flavonoids and the aging brain. Journal of Physiology and Pharmacology 2005; 56: 23-36.
26. Schulz V, Hänsel R, Tyler V E. Rational phytotherapy: a physician’s guide to herbal medicine: Psychology Press, Rational Phytotherapy 2001. [DOI:10.1007/978-3-642-98093-0]
27. Wei P, Li X, Wang S, Dong Y, Yin H, Gu Z, et al. Silibinin ameliorates formaldehyde-induced cognitive impairment by inhibiting oxidative stress. Oxidative Med Cell Longevity 2022; 2022: 5981353. [DOI:10.1155/2022/5981353]
28. Zhang H, Ma Q, Zhang Y w, Xu H. Proteolytic processing of Alzheimer’s β-amyloid precursor protein. Journal of Neurochemistry. 2012; 120: 9-21. [DOI:10.1111/j.1471-4159.2011.07519]

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.