Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
J Cell Mol Med. 2023 May;27(10):1398-1409. doi: 10.1111/jcmm.17740. Epub 2023 Apr 9.
Senescence of vascular endothelial cells is the major risk of vascular dysfunction and disease among elderly people. Parishin, which is a phenolic glucoside derived from Gastrodia elata, significantly prolonged yeast lifespan. However, the action of parishin in vascular ageing remains poorly understood. Here, we treated human coronary artery endothelial cells (HCAEC) and naturally aged mice by parishin. Parishin alleviated HCAEC senescence and general age-related features in vascular tissue in naturally aged mice. Network pharmacology approach was applied to determine the compound-target networks of parishin. Our analysis indicated that parishin had a strong binding affinity for Klotho. Expression of Klotho, a protein of age-related declines, was upregulated by parishin in serum and vascular tissue in naturally aged mice. Furthermore, FoxO1, on Klotho/FoxO1 signalling pathway, was increased in the parishin-intervened group, accompanied by the downregulated phosphorylated FoxO1. Taken together, parishin can increase Klotho expression to alleviate vascular endothelial cell senescence and vascular ageing.
血管内皮细胞衰老(senescence of vascular endothelial cells)是老年人血管功能障碍和疾病的主要风险因素。白皮杉醇(parishin)是一种来源于天麻的酚糖苷,能显著延长酵母的寿命。然而,白皮杉醇在血管老化中的作用尚不清楚。在这里,我们用白皮杉醇处理人冠状动脉内皮细胞(human coronary artery endothelial cells,HCAEC)和自然衰老的小鼠。白皮杉醇缓解了 HCAEC 的衰老和自然衰老小鼠血管组织的一般与年龄相关的特征。我们采用网络药理学方法来确定白皮杉醇的化合物-靶标网络。我们的分析表明,白皮杉醇与 Klotho 具有很强的结合亲和力。Klotho 是一种与年龄相关下降的蛋白质,在自然衰老小鼠的血清和血管组织中,白皮杉醇能上调 Klotho 的表达。此外,Klotho/FoxO1 信号通路中的 FoxO1 在白皮杉醇干预组中增加,同时磷酸化 FoxO1 减少。综上所述,白皮杉醇能增加 Klotho 的表达,从而缓解血管内皮细胞衰老和血管老化。