Salama Abeer, Elgohary Rania
Pharmacology Department, National Research Centre, El-Buhouth St., Cairo, Dokki, 12622, Egypt.
Narcotics, Ergogenics and Poisons Department, National Research Centre, El-Buhouth St., Cairo, Dokki, 12622, Egypt.
Fundam Clin Pharmacol. 2023 Oct;37(5):947-959. doi: 10.1111/fcp.12895. Epub 2023 Apr 17.
Adenosine monophosphate kinase/liver kinase B1/peroxisome proliferator-activated receptor-γ coactivator 1-α (AMPK/LKB1/PGC1α) pathway has a vital role in regulating age-related diseases. It controls neurogenesis, cell proliferation, axon outgrowth, and cellular energy homeostasis. AMPK pathway also regulates mitochondrial synthesis. The current study evaluated the effect of chrysin on D-galactose (D-gal) induced-aging, neuron degeneration, mitochondrial dysfunction, oxidative stress, and neuroinflammation in mice. The mice were allocated randomly into four groups (10 each group): Group 1: normal control group, Group 2: D-gal group, Groups 3 and 4: chrysin (125 and 250 mg/kg, respectively). Groups 2-4 were injected with D-gal (200 mg/kg/day; s.c) for 8 weeks to induce aging. Groups 3 and 4 were orally gavaged every day concurrent with D-gal. At the end of experiment, behavioral, brain biochemical and histopathological changes were monitored. Chrysin administration elevated discrimination ratio in object recognition, Y Maze percentage alternation, locomotor activity and brain contents of AMPK, LKB1, PGC1α, NAD (P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), nerve growth factor (NGF) (neurotrophin-3; NT-3), and seretonin as well as reduced brain contents of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), advanced glycation end products (AGEs) and glial fibrillary acidic protein (GFAP) compared to D-gal-treated mice. Chrysin also alleviated cerebral cortex and white matter neurons degeneration. Chrysin protects against neurodegeneration, improves mitochondrial autophagy and biogenesis as well as activates antioxidant genes expression. In addition, chrysin ameliorates neuroinflammation and stimulates the release of NGF and serotonin neurotransmitter. So, chrysin has a neuroprotective effect in D-gal induced-aging in mice.
腺苷单磷酸激酶/肝脏激酶B1/过氧化物酶体增殖物激活受体γ共激活因子1α（AMPK/LKB1/PGC1α）通路在调节与年龄相关的疾病中起着至关重要的作用。它控制神经发生、细胞增殖、轴突生长和细胞能量稳态。AMPK通路还调节线粒体合成。本研究评估了白杨素对D-半乳糖（D-gal）诱导的小鼠衰老、神经元退化、线粒体功能障碍、氧化应激和神经炎症的影响。将小鼠随机分为四组（每组10只）：第1组：正常对照组，第2组：D-gal组，第3组和第4组：白杨素组（分别为125和250mg/kg）。第2-4组连续8周皮下注射D-gal（200mg/kg/天）以诱导衰老。第3组和第4组在注射D-gal的同时每天进行灌胃。实验结束时，监测行为、脑生化和组织病理学变化。与D-gal处理的小鼠相比，给予白杨素提高了物体识别中的辨别率、Y迷宫百分比交替率、运动活性以及脑内AMPK、LKB1、PGC1α、NAD（P）H醌氧化还原酶1（NQO1）、血红素加氧酶1（HO-1）、神经生长因子（NGF）（神经营养因子-3；NT-3）和血清素的含量，同时降低了脑内肿瘤坏死因子-α（TNF-α）、核因子κB（NF-κB）、晚期糖基化终产物（AGEs）和胶质纤维酸性蛋白（GFAP）的含量。白杨素还减轻了大脑皮质和白质神经元的退化。白杨素可防止神经退行性变，改善线粒体自噬和生物发生，并激活抗氧化基因表达。此外，白杨素可改善神经炎症并刺激NGF和血清素神经递质的释放。因此，白杨素对D-gal诱导的小鼠衰老具有神经保护作用。
