Pharmacology Department, National Research Centre, El-Buhouth St., Dokki, Cairo 12622, Egypt.
Pathology Department, National Research Centre, El-Buhouth St., Dokki, Cairo 12622, Egypt.
Life Sci. 2023 Jul 1;324:121471. doi: 10.1016/j.lfs.2023.121471. Epub 2023 Feb 4.
Aging is the leading risk factor for diminishing lung function, as well as injury and lung disorder. The target of our research was to examine the potential protective effect of naringin and the possible role of SIRT1 in mice with D-galactose-induced lung aging, by evaluating its effects on antioxidant systems, mitochondrial biogenesis, autophagy, and apoptosis, by referring to the potential involvement of Nrf2/NQO1, LKB1/AMPK/PGC-1α, FOXO1, and P53/caspase-3 signaling.
The mice were randomly sorted into 5 groups (10 each): 1st normal group received subcutaneous normal saline and intragastric distilled water, 2nd naringin 300 mg/kg orally, 3rd D-galactose (200 mg/kg/day) was administered subcutaneously into mice for eight weeks, to accelerate aging, 4th & 5th: oral naringin (150, 300 mg/kg) was given daily concurrently with D-galactose injection for 8 weeks.
In silico investigation revealed that naringin substantially stimulates the SIRT1 and AMPK molecules. At the molecular level, our findings indicated that treatment with naringin stimulated the mitochondrial biogenesis pathway through regulation of the LKB1/AMPK/PGC-1α signals and upregulated FOXO1-mediated autophagy. Furthermore, naringin exhibited antioxidant properties by activating the Nrf2/NQO1 pathway and inhibiting MDA and AGEs levels. In addition, Naringin ameliorated alveolar spaces destruction and bronchial wall thickening, as well as alleviated P53/caspase-3 apoptosis signaling.
Naringin exerts protective effects against D-galactose-induced lung aging and enhances longevity by activating SIRT1. SIRT1 regulates various aging-related molecular pathways via restoring pro-oxidant/antioxidant homeostasis, activation of mitochondrial biogenesis, modulating of autophagy and inhibition of apoptosis.
衰老可导致肺功能下降、损伤和肺部疾病，是导致这些疾病的主要危险因素。本研究旨在通过观察其对抗氧化系统、线粒体生物发生、自噬和细胞凋亡的影响，探讨柚皮苷对 D-半乳糖诱导的肺衰老小鼠的潜在保护作用及其作用机制，探讨 SIRT1 可能的作用。Nrf2/NQO1、LKB1/AMPK/PGC-1α、FOXO1 和 P53/caspase-3 信号通路可能参与其中。
将小鼠随机分为 5 组（每组 10 只）：1 组给予皮下生理盐水和灌胃蒸馏水，2 组给予柚皮苷 300mg/kg 灌胃，3 组给予皮下 D-半乳糖（200mg/kg/天）8 周加速衰老，4 组和 5 组：同时给予 D-半乳糖皮下注射 8 周，每天给予柚皮苷（150、300mg/kg）灌胃。
计算机模拟研究表明，柚皮苷可显著刺激 SIRT1 和 AMPK 分子。在分子水平上，我们的研究结果表明，柚皮苷通过调节 LKB1/AMPK/PGC-1α 信号通路刺激线粒体生物发生途径，并上调 FOXO1 介导的自噬。此外，柚皮苷通过激活 Nrf2/NQO1 通路和抑制 MDA 和 AGEs 水平发挥抗氧化作用。此外，柚皮苷改善了肺泡空间破坏和支气管壁增厚，并减轻了 P53/caspase-3 凋亡信号。
柚皮苷通过激活 SIRT1 对 D-半乳糖诱导的肺衰老具有保护作用，并延长寿命。SIRT1 通过恢复氧化应激/抗氧化平衡、激活线粒体生物发生、调节自噬和抑制细胞凋亡来调节多种与衰老相关的分子途径。
