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Xanthoceraside attenuates amyloid β peptide1-42-induced memory impairments by reducing neuroinflammatory responses in mice.
Eur J Pharmacol. 2018 Feb 05; 820:18-30.EJ

Abstract

Xanthoceraside, a novel triterpenoid saponin extracted from the husks of Xanthoceras sorbifolia Bunge, has neuroprotective effects in vivo and anti-inflammatory properties in vitro. However, the exact mechanism of xanthoceraside on anti-amyloid beta (Aβ)-induced neuroinflammatory responses has not been elucidated. Therefore, we used intracerebroventricular injection of amyloid 1-42 (Aβ1-42) to establish a mouse model to test the effects of xanthoceraside on Aβ-induced cognitive impairments and the TLR2/NF-κB and MAPK pathways. The mice received xanthoceraside (0.02, 0.08 or 0.32mg/kg) or vehicle from the day of Aβ1-42 injection. The Morris water maze test was performed 4 days after Aβ1-42 injection. The levels of inflammatory cytokines (interleukin (IL)-6 and IL-4) were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of glial fibrillary acidic protein (GFAP) and cluster of differentiation 11b (CD11b) in the hippocampus were determined with an immunohistochemistry assay. Inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) were analysed by Western blotting; iNOS, COX-2 and Toll-like receptor 2 (TLR2) mRNA expression levels were measured by reverse transcription-polymerase chain reaction (RT-PCR). Here, we observed that xanthoceraside at doses of 0.08 and 0.32mg/kg significantly improved learning and memory impairments and significantly inhibited GFAP and CD11b overexpression induced by Aβ1-42 in mice. ELISA results revealed that xanthoceraside suppressed IL-6 release and increased IL-4 levels. Western blotting results showed that xanthoceraside reduced iNOS and COX-2 protein levels in hippocampus; xanthoceraside also inhibited translocation of NF-κB p50 and p65 into the nucleus and phosphorylation of extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38. RT-PCR confirmed that xanthoceraside decreased iNOS, COX-2 and TLR2 mRNA levels. These results suggest that xanthoceraside inhibition of the TLR2 pathway and down-regulation of MAPK and NF-κB activities may be related to the improvement in learning and memory impairments.

Authors+Show Affiliations

Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Department of Pharmacology, The Second Hospital Affiliated to Liaoning Chinese Medical University, Shenyang 110034, PR China.Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.Shenyang Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, PR China.Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: Libozou@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29229533

Citation

Qi, Yue, et al. "Xanthoceraside Attenuates Amyloid Β Peptide1-42-induced Memory Impairments By Reducing Neuroinflammatory Responses in Mice." European Journal of Pharmacology, vol. 820, 2018, pp. 18-30.
Qi Y, Ji XF, Chi TY, et al. Xanthoceraside attenuates amyloid β peptide1-42-induced memory impairments by reducing neuroinflammatory responses in mice. Eur J Pharmacol. 2018;820:18-30.
Qi, Y., Ji, X. F., Chi, T. Y., Liu, P., Jin, G., Xu, Q., Jiao, Q., Wang, L. H., & Zou, L. B. (2018). Xanthoceraside attenuates amyloid β peptide1-42-induced memory impairments by reducing neuroinflammatory responses in mice. European Journal of Pharmacology, 820, 18-30. https://doi.org/10.1016/j.ejphar.2017.11.045
Qi Y, et al. Xanthoceraside Attenuates Amyloid Β Peptide1-42-induced Memory Impairments By Reducing Neuroinflammatory Responses in Mice. Eur J Pharmacol. 2018 Feb 5;820:18-30. PubMed PMID: 29229533.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Xanthoceraside attenuates amyloid β peptide1-42-induced memory impairments by reducing neuroinflammatory responses in mice. AU - Qi,Yue, AU - Ji,Xue-Fei, AU - Chi,Tian-Yan, AU - Liu,Peng, AU - Jin,Ge, AU - Xu,Qian, AU - Jiao,Qing, AU - Wang,Li-Hua, AU - Zou,Li-Bo, Y1 - 2017/12/08/ PY - 2017/07/03/received PY - 2017/11/23/revised PY - 2017/11/28/accepted PY - 2017/12/13/pubmed PY - 2018/8/7/medline PY - 2017/12/13/entrez KW - Alzheimer's disease KW - Cytokine KW - Mitogen-activated protein kinase KW - Nuclear factor-kappa B KW - Toll-like receptor 2 KW - Xanthoceraside SP - 18 EP - 30 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 820 N2 - Xanthoceraside, a novel triterpenoid saponin extracted from the husks of Xanthoceras sorbifolia Bunge, has neuroprotective effects in vivo and anti-inflammatory properties in vitro. However, the exact mechanism of xanthoceraside on anti-amyloid beta (Aβ)-induced neuroinflammatory responses has not been elucidated. Therefore, we used intracerebroventricular injection of amyloid 1-42 (Aβ1-42) to establish a mouse model to test the effects of xanthoceraside on Aβ-induced cognitive impairments and the TLR2/NF-κB and MAPK pathways. The mice received xanthoceraside (0.02, 0.08 or 0.32mg/kg) or vehicle from the day of Aβ1-42 injection. The Morris water maze test was performed 4 days after Aβ1-42 injection. The levels of inflammatory cytokines (interleukin (IL)-6 and IL-4) were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of glial fibrillary acidic protein (GFAP) and cluster of differentiation 11b (CD11b) in the hippocampus were determined with an immunohistochemistry assay. Inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) were analysed by Western blotting; iNOS, COX-2 and Toll-like receptor 2 (TLR2) mRNA expression levels were measured by reverse transcription-polymerase chain reaction (RT-PCR). Here, we observed that xanthoceraside at doses of 0.08 and 0.32mg/kg significantly improved learning and memory impairments and significantly inhibited GFAP and CD11b overexpression induced by Aβ1-42 in mice. ELISA results revealed that xanthoceraside suppressed IL-6 release and increased IL-4 levels. Western blotting results showed that xanthoceraside reduced iNOS and COX-2 protein levels in hippocampus; xanthoceraside also inhibited translocation of NF-κB p50 and p65 into the nucleus and phosphorylation of extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38. RT-PCR confirmed that xanthoceraside decreased iNOS, COX-2 and TLR2 mRNA levels. These results suggest that xanthoceraside inhibition of the TLR2 pathway and down-regulation of MAPK and NF-κB activities may be related to the improvement in learning and memory impairments. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/29229533/Xanthoceraside_attenuates_amyloid_β_peptide1_42_induced_memory_impairments_by_reducing_neuroinflammatory_responses_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(17)30777-X DB - PRIME DP - Unbound Medicine ER -