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Geniposide ameliorates learning memory deficits, reduces tau phosphorylation and decreases apoptosis via GSK3β pathway in streptozotocin-induced alzheimer rat model.
Brain Pathol. 2014 Apr; 24(3):261-9.BP

Abstract

Intracerebral-ventricular (ICV) injection of streptozotocin (STZ) induces an insulin-resistant brain state that may underlie the neural pathogenesis of sporadic Alzheimer disease (AD). Our previous work showed that prior ICV treatment of glucagon-like peptide-1 (GLP-1) could prevent STZ-induced learning memory impairment and tau hyperphosphorylation in the rat brain. The Chinese herbal medicine geniposide is known to relieve symptoms of type 2 diabetes. Because geniposide is thought to act as a GLP-1 receptor agonist, we investigated the potential therapeutic effect of geniposide on STZ-induced AD model in rats. Our result showed that a single injection of geniposide (50 μM, 10 μL) to the lateral ventricle prevented STZ-induced spatial learning deficit by about 40% and reduced tau phosphorylation by about 30% with Morris water maze test and quantitative immunohistochemical analysis, respectively. It has been known that tau protein can be phosphorylated by glycogen synthase kinase-3 (GSK3) and STZ can increase the activity of GSK3β. Our result with Western blot analysis showed that central administration of geniposide resulted in an elevated expression of GSK3β(pS-9) but suppressed GSK3β(pY-216) indicating that geniposide reduced STZ-induced GSK3β hyperactivity. In addition, ultrastructure analysis showed that geniposide averted STZ-induced neural pathology, including paired helical filament (PHF)-like structures, accumulation of vesicles in synaptic terminal, abnormalities of endoplasmic reticulum (ER) and early stage of apoptosis. In summary, our study suggests that the water soluble and orally active monomer of Chinese herbal medicine geniposide may serve as a novel therapeutic agent for the treatment of sporadic AD.

Authors+Show Affiliations

Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

24329968

Citation

Gao, Chong, et al. "Geniposide Ameliorates Learning Memory Deficits, Reduces Tau Phosphorylation and Decreases Apoptosis Via GSK3β Pathway in Streptozotocin-induced Alzheimer Rat Model." Brain Pathology (Zurich, Switzerland), vol. 24, no. 3, 2014, pp. 261-9.
Gao C, Liu Y, Jiang Y, et al. Geniposide ameliorates learning memory deficits, reduces tau phosphorylation and decreases apoptosis via GSK3β pathway in streptozotocin-induced alzheimer rat model. Brain Pathol. 2014;24(3):261-9.
Gao, C., Liu, Y., Jiang, Y., Ding, J., & Li, L. (2014). Geniposide ameliorates learning memory deficits, reduces tau phosphorylation and decreases apoptosis via GSK3β pathway in streptozotocin-induced alzheimer rat model. Brain Pathology (Zurich, Switzerland), 24(3), 261-9. https://doi.org/10.1111/bpa.12116
Gao C, et al. Geniposide Ameliorates Learning Memory Deficits, Reduces Tau Phosphorylation and Decreases Apoptosis Via GSK3β Pathway in Streptozotocin-induced Alzheimer Rat Model. Brain Pathol. 2014;24(3):261-9. PubMed PMID: 24329968.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Geniposide ameliorates learning memory deficits, reduces tau phosphorylation and decreases apoptosis via GSK3β pathway in streptozotocin-induced alzheimer rat model. AU - Gao,Chong, AU - Liu,Yueze, AU - Jiang,Yuanhong, AU - Ding,Jianming, AU - Li,Lin, Y1 - 2014/02/12/ PY - 2013/10/01/received PY - 2013/12/06/revised PY - 2013/12/17/entrez PY - 2013/12/18/pubmed PY - 2014/12/15/medline KW - Alzheimer's disease KW - geniposide KW - glucagon-like peptide-1 receptor KW - glycogen synthase kinase-3β KW - tau hyperphosphorylation KW - type 2 diabetes SP - 261 EP - 9 JF - Brain pathology (Zurich, Switzerland) JO - Brain Pathol. VL - 24 IS - 3 N2 - Intracerebral-ventricular (ICV) injection of streptozotocin (STZ) induces an insulin-resistant brain state that may underlie the neural pathogenesis of sporadic Alzheimer disease (AD). Our previous work showed that prior ICV treatment of glucagon-like peptide-1 (GLP-1) could prevent STZ-induced learning memory impairment and tau hyperphosphorylation in the rat brain. The Chinese herbal medicine geniposide is known to relieve symptoms of type 2 diabetes. Because geniposide is thought to act as a GLP-1 receptor agonist, we investigated the potential therapeutic effect of geniposide on STZ-induced AD model in rats. Our result showed that a single injection of geniposide (50 μM, 10 μL) to the lateral ventricle prevented STZ-induced spatial learning deficit by about 40% and reduced tau phosphorylation by about 30% with Morris water maze test and quantitative immunohistochemical analysis, respectively. It has been known that tau protein can be phosphorylated by glycogen synthase kinase-3 (GSK3) and STZ can increase the activity of GSK3β. Our result with Western blot analysis showed that central administration of geniposide resulted in an elevated expression of GSK3β(pS-9) but suppressed GSK3β(pY-216) indicating that geniposide reduced STZ-induced GSK3β hyperactivity. In addition, ultrastructure analysis showed that geniposide averted STZ-induced neural pathology, including paired helical filament (PHF)-like structures, accumulation of vesicles in synaptic terminal, abnormalities of endoplasmic reticulum (ER) and early stage of apoptosis. In summary, our study suggests that the water soluble and orally active monomer of Chinese herbal medicine geniposide may serve as a novel therapeutic agent for the treatment of sporadic AD. SN - 1750-3639 UR - https://www.unboundmedicine.com/medline/citation/24329968/Geniposide_ameliorates_learning_memory_deficits_reduces_tau_phosphorylation_and_decreases_apoptosis_via_GSK3β_pathway_in_streptozotocin_induced_alzheimer_rat_model_ L2 - https://doi.org/10.1111/bpa.12116 DB - PRIME DP - Unbound Medicine ER -