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Neuroprotective and mechanistic study of GJ-4 on okadaic acid-induced memory impairment in mice
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Yang YANG, Chan-juan SHENG, Cai-xia ZANG, Jun-mei SHANG, Xiu-qi BAO, Dan ZHANG*
Acta Pharmaceutica Sinica | 2023, 58(12) : 3628 - 3636
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Acta Pharmaceutica Sinica | 2023, 58(12): 3628-3636
Neuroprotective and mechanistic study of GJ-4 on okadaic acid-induced memory impairment in mice
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Yang YANG, Chan-juan SHENG, Cai-xia ZANG, Jun-mei SHANG, Xiu-qi BAO, Dan ZHANG*
Affiliations
  • State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Published: 2023-12-12 doi: 10.16438/j.0513-4870.2023-1201
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GJ-4 is crocin enrichments extracted from Gardenia jasminoides J. Ellis, and our previous studies have shown that GJ-4 significantly improved learning and memory impairment induced by Aβ in mice. Herein, a memory deficit model was developed by injecting okadaic acid (OA) into the lateral ventricle of mice, and the neuroprotection and underlying mechanism of GJ-4 on neuronal injury caused by Tau hyperphosphorylation were investigated. The Animal Care & Welfare Committee, Institute of Materia Medica, CAMS & PUMC has approved all procedures (No.00000318). GJ-4 at different doses was intragastric administration to mice for 16 days. Step-down test and Morris water maze test showed that GJ-4 could significantly improve OA-induced memory impairment in mice, and reduced the loss of Nissl bodies in the hippocampus of mice. GJ-4 could also decrease the phosphorylation level of Tau protein at Ser396, Thr231 and Ser404 via increasing protein phosphatase 2A (PP2A) activity and inhibiting glycogen synthase kinase-3β (GSK-3β) activity. Besides, further researches indicated that GJ-4 could inhibit the level of oxidative stress in the brain of OA mice, reduce neuronal apoptosis and inhibit the neuroinflammation mediated by activation of astrocytes in the hippocampus of mice, and eventually achieve its effects in improving learning and memory impairment in mice. According to these findings, we anticipated that GJ-4 might be a potential therapeutic drug for Alzheimer's disease.

Alzheimer disease  /  GJ-4  /  Tau protein  /  okadaic acid  /  neuroinflammation
Yang YANG, Chan-juan SHENG, Cai-xia ZANG, Jun-mei SHANG, Xiu-qi BAO, Dan ZHANG. Neuroprotective and mechanistic study of GJ-4 on okadaic acid-induced memory impairment in mice[J]. Acta Pharmaceutica Sinica, 2023 , 58 (12) : 3628 -3636 . DOI: 10.16438/j.0513-4870.2023-1201
Year 2023 volume 58 Issue 12
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doi: 10.16438/j.0513-4870.2023-1201
  • Receive Date:2023-10-26
  • Online Date:2025-11-21
  • Published:2023-12-12
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  • Received:2023-10-26
  • Revised:2023-11-07
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    State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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