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Silibinin attenuates amyloid beta(25-35) peptide-induced memory impairments: implication of inducible nitric-oxide synthase and tumor necrosis factor-alpha in mice.
J Pharmacol Exp Ther. 2009 Oct; 331(1):319-26.JP

Abstract

In Alzheimer's disease (AD), the deposition of amyloid peptides is invariably associated with oxidative stress and inflammatory responses. Silibinin (silybin), a flavonoid derived from the herb milk thistle, has potent anti-inflammatory and antioxidant activities. However, it remains unclear whether silibinin improves amyloid beta (Abeta) peptide-induced neurotoxicity. In this study, we examined the effect of silibinin on the fear-conditioning memory deficits, inflammatory response, and oxidative stress induced by the intracerebroventricular injection of Abeta peptide(25-35) (Abeta(25-35)) in mice. Mice were treated with silibinin (2, 20, and 200 mg/kg p.o., once a day for 8 days) from the day of the Abeta(25-35) injection (day 0). Memory function was evaluated in cued and contextual fear-conditioning tests (day 6). Nitrotyrosine levels in the hippocampus and amygdala were examined (day 8). The mRNA expression of inducible nitric-oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in the hippocampus and amygdala was measured 2 h after the Abeta(25-35) injection. We found that silibinin significantly attenuated memory deficits caused by Abeta(25-35) in the cued and contextual fear-conditioning test. Silibinin significantly inhibited the increase in nitrotyrosine levels in the hippocampus and amygdala induced by Abeta(25-35). Nitrotyrosine levels in these regions were negatively correlated with memory performance. Moreover, real-time RT-PCR revealed that silibinin inhibited the overexpression of iNOS and TNF-alpha mRNA in the hippocampus and amygdala induced by Abeta(25-35). These findings suggest that silibinin (i) attenuates memory impairment through amelioration of oxidative stress and inflammatory response induced by Abeta(25-35) and (ii) may be a potential candidate for an AD medication.

Authors+Show Affiliations

Department of Chemical Pharmacology, Meijo University, Nagoya, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19638571

Citation

Lu, P, et al. "Silibinin Attenuates Amyloid Beta(25-35) Peptide-induced Memory Impairments: Implication of Inducible Nitric-oxide Synthase and Tumor Necrosis Factor-alpha in Mice." The Journal of Pharmacology and Experimental Therapeutics, vol. 331, no. 1, 2009, pp. 319-26.
Lu P, Mamiya T, Lu LL, et al. Silibinin attenuates amyloid beta(25-35) peptide-induced memory impairments: implication of inducible nitric-oxide synthase and tumor necrosis factor-alpha in mice. J Pharmacol Exp Ther. 2009;331(1):319-26.
Lu, P., Mamiya, T., Lu, L. L., Mouri, A., Niwa, M., Hiramatsu, M., Zou, L. B., Nagai, T., Ikejima, T., & Nabeshima, T. (2009). Silibinin attenuates amyloid beta(25-35) peptide-induced memory impairments: implication of inducible nitric-oxide synthase and tumor necrosis factor-alpha in mice. The Journal of Pharmacology and Experimental Therapeutics, 331(1), 319-26. https://doi.org/10.1124/jpet.109.155069
Lu P, et al. Silibinin Attenuates Amyloid Beta(25-35) Peptide-induced Memory Impairments: Implication of Inducible Nitric-oxide Synthase and Tumor Necrosis Factor-alpha in Mice. J Pharmacol Exp Ther. 2009;331(1):319-26. PubMed PMID: 19638571.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Silibinin attenuates amyloid beta(25-35) peptide-induced memory impairments: implication of inducible nitric-oxide synthase and tumor necrosis factor-alpha in mice. AU - Lu,P, AU - Mamiya,T, AU - Lu,L L, AU - Mouri,A, AU - Niwa,M, AU - Hiramatsu,M, AU - Zou,L B, AU - Nagai,T, AU - Ikejima,T, AU - Nabeshima,T, Y1 - 2009/07/28/ PY - 2009/7/30/entrez PY - 2009/7/30/pubmed PY - 2009/10/14/medline SP - 319 EP - 26 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 331 IS - 1 N2 - In Alzheimer's disease (AD), the deposition of amyloid peptides is invariably associated with oxidative stress and inflammatory responses. Silibinin (silybin), a flavonoid derived from the herb milk thistle, has potent anti-inflammatory and antioxidant activities. However, it remains unclear whether silibinin improves amyloid beta (Abeta) peptide-induced neurotoxicity. In this study, we examined the effect of silibinin on the fear-conditioning memory deficits, inflammatory response, and oxidative stress induced by the intracerebroventricular injection of Abeta peptide(25-35) (Abeta(25-35)) in mice. Mice were treated with silibinin (2, 20, and 200 mg/kg p.o., once a day for 8 days) from the day of the Abeta(25-35) injection (day 0). Memory function was evaluated in cued and contextual fear-conditioning tests (day 6). Nitrotyrosine levels in the hippocampus and amygdala were examined (day 8). The mRNA expression of inducible nitric-oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in the hippocampus and amygdala was measured 2 h after the Abeta(25-35) injection. We found that silibinin significantly attenuated memory deficits caused by Abeta(25-35) in the cued and contextual fear-conditioning test. Silibinin significantly inhibited the increase in nitrotyrosine levels in the hippocampus and amygdala induced by Abeta(25-35). Nitrotyrosine levels in these regions were negatively correlated with memory performance. Moreover, real-time RT-PCR revealed that silibinin inhibited the overexpression of iNOS and TNF-alpha mRNA in the hippocampus and amygdala induced by Abeta(25-35). These findings suggest that silibinin (i) attenuates memory impairment through amelioration of oxidative stress and inflammatory response induced by Abeta(25-35) and (ii) may be a potential candidate for an AD medication. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/19638571/Silibinin_attenuates_amyloid_beta_25_35__peptide_induced_memory_impairments:_implication_of_inducible_nitric_oxide_synthase_and_tumor_necrosis_factor_alpha_in_mice_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=19638571 DB - PRIME DP - Unbound Medicine ER -