Wogonin ameliorates Aβ1-42 and D-galactose-induced learning and memory impairment in mice
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摘要:
研究汉黄芩素对小鼠学习记忆的改善作用。分别采用侧脑室注射Aβ1-42建立小鼠学习记忆损害模型与腹腔注射D-半乳糖建立小鼠急性衰老模型，连续28 d灌胃给予75、150和300 mg/kg汉黄芩素，采用Morris水迷宫、新物体识别、旷场实验检测汉黄芩素对小鼠学习记忆的影响。结果显示，在Aβ1-42诱导的学习记忆损害模型中，与模型组相比，150 mg/kg和300 mg/kg汉黄芩素给药组小鼠在新物体识别实验中对新物体的识别指数显著增加；150 mg/kg汉黄芩素给药组小鼠在Morris水迷宫实验测试期目标象限停留时间百分比显著增加，而在旷场实验中各组小鼠的运动总距离无显著变化。在D-半乳糖诱导的急性衰老模型中，与模型组相比，150 mg/kg汉黄芩素组小鼠在Morris水迷宫实验测试期穿越平台次数显著增加，75、150和300 mg/kg汉黄芩素组小鼠在Morris水迷宫实验测试期目标象限停留时间百分比显著增加；而在旷场实验中各组小鼠的运动总距离无显著变化。研究提示汉黄芩素对Aβ1-42和D-半乳糖诱导的小鼠学习记忆损害均具有改善作用，并对小鼠自发活动无显著影响。此外，采用Western blot实验检测发现，汉黄芩素可显著减少Aβ1-42和D-半乳糖诱导的小鼠海马区神经细胞凋亡。这些结果表明，汉黄芩素可能对阿尔茨海默病和衰老相关的学习记忆损害具有改善作用。
Abstract:To investigate the effects of Wogonin (WO) on learning and memory impairment, Aβ1-42 was injected intracerebroventricularly to induced a mouse learning and memory impairment model, and D-galactose was injected intraperitoneally to induced a mouse acute aging model. Mice were administered WO (75, 150, or 300 mg/kg) by oral gavage for 28 consecutive days. Cognitive function was assessed using the Morris water maze (MWM), novel object recognition (NOR), and open field tests (OFT). In the Aβ1-42 model, WO treatment (150 and 300 mg/kg) significantly improved the recognition index in the NOR test, while the 150 mg/kg group showed increased target quadrant preference in the MWM test. No changes in the total distance traveled in OFT. In the D-galactose aging model, the 150 mg/kg WO group exhibited increased platform crossings in the MWM test, and all WO doses (75, 150, and 300 mg/kg) enhanced target quadrant preference, with no alterations in spontaneous movement. Western blot analysis revealed that WO significantly attenuated hippocampal apoptosis in both models. These findings suggest that WO ameliorates learning and memory impairment associated with Alzheimer’s disease and aging.
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Keywords:
- wogonin /
- Aβ1-42 /
- D-galactose /
- memory impairment /
- apoptosis
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Figure 1. Effect of wogonin (WO) on spontaneous activity in mice
A: Total distance in each group of Aβ1-42 -induced learning and memory impairment mice in open field test (mean$ \pm $SEM, n=6-7); B: Total distance in each group of D-galactose-induced acute aging mice in open field test (mean$ \pm $SEM, n=6) CON：Control；DPZ：Donepezil；MET:Metformin
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Figure 2. Effect of wogonin on working memory in Aβ1-42-induced learning and memory impairment mice (A, B) and D-galactose-induced acute aging mice (C, D). A: Discrimination index in new object recognition (NOR) test (mean$ \pm $SEM, n=4-6); B: Representative tracks in NOR test; C: Discrimination index in NOR test (mean$ \pm $SEM, n=6-8); D: Representative tracks in NOR test
*P<0.05, **P<0.01 vs Aβ1-42 or D-gal group
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Figure 3. Effect of wogonin on spatial learning and memory in Aβ1-42-induced learning and memory impairment mice
A: Escape latency to the visible platform of Morris water maze (MWM) test; B: Escape latency to the hidden platform of MWM test; C: Number of platform location crossings during the probe trial (mean$ \pm $SEM, n=5-7); D: Percentage of time spent in the target quadrant during the probe trial (mean$ \pm $SEM, n=7-10). E: Representative swimming path during the probe trial*P<0.05, **P<0.01, ***P<0.001 vs Aβ1-42 group
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Figure 4. Effect of wogonin on spatial learning and memory in D-galactose-induced acute aging mice.
A: Escape latency to the visible platform of MWM test; B: Escape latency to the hidden platform of MWM test; C: Number of platform location crossings during the probe trial (mean$ \pm $SEM, n=7); D: Percentage of time spent in the target quadrant during the probe trial (mean$ \pm $SEM, n=6-7). E: Representative swimming path during the probe trial*P<0.05, **P<0.01, ***P<0.001 vs D-gal group
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Figure 5. Effect of wogonin on apoptosis in Aβ1-42-induced learning memory impairment mice (A-D) and D-galactose-induced acute aging mice (E-H)
A: Representative bands of Bcl-2, Bax and Cleaved caspase-3 in the hippocampus in Aβ1-42 model; B-D: Quantification of Bcl-2, Bax and Cleaved caspase-3 protein levels in Aβ1-42 model(mean$ \pm $SEM, n=5); E: Representative bands of Bcl-2, Bax and cleaved caspase-3 in the hippocampus in D-galactose model; F-H: Quantification of Bcl-2, Bax and cleaved caspase-3 protein levels in D-galactose model（mean$ \pm $SEM, n=5）*P<0.05, **P<0.01, ***P<0.001 vs Aβ1-42 or D-gal group
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[1] Kong ZH, Shen QL, Jiang J, et al. Wogonin improves functional neuroprotection for acute cerebral ischemia in rats by promoting angiogenesis via TGF-β1[J]. Ann Transl Med, 2019, 7(22): 639. doi: 10.21037/atm.2019.10.70
[2] Liu YF, Zhang MB, Zeng L, et al. Wogonin upregulates SOCS3 to alleviate the injury in diabetic nephropathy by inhibiting TLR4-mediated JAK/STAT/AIM2 signaling pathway[J]. Mol Med, 2024, 30(1): 78. doi: 10.1186/s10020-024-00845-4
[3] Sun YN, Guo WJ, Guo YJ, et al. Apoptosis induction in human prostate cancer cells related to the fatty acid metabolism by wogonin-mediated regulation of the AKT-SREBP1-FASN signaling network[J]. Food Chem Toxicol, 2022, 169: 113450. doi: 10.1016/j.fct.2022.113450
[4] Pan L, Cho KS, Yi I, et al. Baicalein, baicalin, and wogonin: protective effects against ischemia-induced neurodegeneration in the brain and retina[J]. Oxid Med Cell Longev, 2021, 2021: 8377362. doi: 10.1155/2021/8377362
[5] Lee B, Sur B, Cho SG, et al. Wogonin attenuates hippocampal neuronal loss and cognitive dysfunction in trimethyltin-intoxicated rats[J]. Biomol Ther (Seoul), 2016, 24(3): 328-337. doi: 10.4062/biomolther.2015.152
[6] Guo XY, Wang JY, Wang NN, et al. Wogonin preventive impact on hippocampal neurodegeneration, inflammation and cognitive defects in temporal lobe epilepsy[J]. Saudi J Biol Sci, 2020, 27(8): 2149-2156. doi: 10.1016/j.sjbs.2020.05.030
[7] Huang WG, Jiang WK, Shao YW, et al. Reward effect of flubromazolam and its underlying neural circuit mechanism[J]. J China Pharm Univ (中国药科大学学报), 2024, 55(3): 390-396. [8] Ali T, Kim MO. Melatonin ameliorates amyloid beta-induced memory deficits, tau hyperphosphorylation and neurodegeneration via PI3/Akt/GSk3β pathway in the mouse hippocampus[J]. J Pineal Res, 2015, 59(1): 47-59. doi: 10.1111/jpi.12238
[9] Monteiro KLC, Dos Santos Alcântara MG, Freire NML, et al. BACE-1 inhibitors targeting Alzheimer’s disease[J]. Curr Alzheimer Res, 2023, 20(3): 131-148. doi: 10.2174/1567205020666230612155953
[10] Johnson ECB, Bian SJ, Haque RU, et al. Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease[J]. Nat Med, 2023, 29(8): 1979-1988. doi: 10.1038/s41591-023-02476-4
[11] Fan M, Liu S, Sun HM, et al. Bilateral intracerebroventricular injection of streptozotocin induces AD-like behavioral impairments and neuropathological features in mice: Involved with the fundamental role of neuroinflammation[J]. Biomed Pharmacother, 2022, 153: 113375. doi: 10.1016/j.biopha.2022.113375
[12] Li YM, Zhang J, Wan JL, et al. Melatonin regulates Aβ production/clearance balance and Aβ neurotoxicity: a potential therapeutic molecule for Alzheimer’s disease[J]. Biomed Pharmacother, 2020, 132: 110887. doi: 10.1016/j.biopha.2020.110887
[13] Thal DR, Rüb U, Orantes M, et al. Phases of A beta-deposition in the human brain and its relevance for the development of AD[J]. Neurology, 2002, 58(12): 1791-1800. doi: 10.1212/WNL.58.12.1791
[14] Mao X, Liao ZZ, Guo L, et al. Schisandrin C ameliorates learning and memory deficits by Aβ1-42-induced oxidative stress and neurotoxicity in mice[J]. Phytother Res, 2015, 29(9): 1373-1380. doi: 10.1002/ptr.5390
[15] Burns EA, Leventhal EA. Aging, immunity, and cancer[J]. Cancer Control, 2000, 7(6): 513-522. doi: 10.1177/107327480000700603
[16] Miller RA. The aging immune system: primer and prospectus[J]. Science, 1996, 273(5271): 70-74. doi: 10.1126/science.273.5271.70
[17] Lu J, Wu DM, Zheng YL, et al. Ursolic acid attenuates D-galactose-induced inflammatory response in mouse prefrontal cortex through inhibiting AGEs/RAGE/NF-κB pathway activation[J]. Cereb Cortex, 2010, 20(11): 2540-2548. doi: 10.1093/cercor/bhq002
[18] Wu DM, Lu J, Zheng YL, et al. Purple sweet potato color repairs d-galactose-induced spatial learning and memory impairment by regulating the expression of synaptic proteins[J]. Neurobiol Learn Mem, 2008, 90(1): 19-27. doi: 10.1016/j.nlm.2008.01.010
[19] Pertynska-Marczewska M, Diamanti-Kandarakis E. Aging ovary and the role for advanced glycation end products[J]. Menopause, 2017, 24(3): 345-351. doi: 10.1097/GME.0000000000000755
[20] Aisa B, Tordera R, Lasheras B, et al. Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats[J]. Psychoneuroendocrinology, 2007, 32(3): 256-266. doi: 10.1016/j.psyneuen.2006.12.013
[21] Morris R. Developments of a water-maze procedure for studying spatial learning in the rat[J]. J Neurosci Meth, 1984, 11(1): 47-60. doi: 10.1016/0165-0270(84)90007-4
[22] Lee W, Ku SK, Bae JS. Anti-inflammatory effects of Baicalin, Baicalein, and Wogonin in vitro and in vivo[J]. Inflammation, 2015, 38(1): 110-125. doi: 10.1007/s10753-014-0013-0
[23] Lu LH, Li YN, Dong Q, et al. Wogonin inhibits oxidative stress and vascular calcification via modulation of heme oxygenase-1[J]. Eur J Pharmacol, 2023, 958: 176070. doi: 10.1016/j.ejphar.2023.176070
[24] Shao WB, Zhang CX, Li K, et al. Wogonin inhibits inflammation and apoptosis through STAT3 signal pathway to promote the recovery of spinal cord injury[J]. Brain Res, 2022, 1782: 147843. doi: 10.1016/j.brainres.2022.147843
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