Ren Bingjie, Wang Mengmeng, Hao Danli, Wang Zhimin, Dai Liping
Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, University of Chinese Medicine, Henan, Henan Province, 450046, China.
Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, University of Chinese Medicine, Henan, Henan Province, 450046, China; Engineering Technology Research Center for Comprehensive Development and Utilization of Authentic Medicinal Materials from Henan, Henan, 450046, China.
J Ethnopharmacol. 2025 Jun 19;352:120156. doi: 10.1016/j.jep.2025.120156.
Dendrobium officinale Kimura et Migo (D. officinale), a staple in Traditional Chinese Medicine, has been utilized for centuries and is renowned for its properties in nourishing yin, tonifying the kidneys, and promoting fluid production to benefit the stomach. In recent years, modern pharmacological studies have substantiated its potential in anti-aging and renal protection, highlighting its therapeutic relevance in both traditional and contemporary contexts.
This study aimed to investigate the impacts and possible mechanism of Dendrobium officinale in ameliorating aging-induced kidney injury.
Antioxidant activity of Dendrobium officinale Kimura et Migo extract (DOE) were assessed using DPPH and ABTS radical scavenging methods. D-galactose (D-gal) induced kidney aging model and HO induced NRK-52E cells model were established to evaluate extract of DOE pharmacodynamics in vitro and vivo. Cell viability and senescence of NRK-52E cell were detected by MTT assay and β-Galactosidase (SA-β-Gal) staining, respectively. H&E, kidney index and serum nephrotoxicity markers analysis were used to evaluate the protective effects of DOE. The concentrations of ROS, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and catalas (CAT) were assessed both in vivo and in vitro. Utilizing network pharmacology, we identified the key chemical constituents and potential target genes of DOE. To validate the efficacy of these targets within the relevant pathways, we conducted molecular docking studies alongside western blotting and Real-time quantitative PCR analysis.
DOE treatment markedly increased the viability and reduced the SA-β-Gal-positive rate of NRK-52E cells as compared to the HO group. DOE significantly improved the general condition of the mice, including increased the kidney index, reduced the urinary protein concentration, the blood urea nitrogen (BUN), creatinine content (CRE) and improved kidney tissue injury. Furthermore, DOE treatment significantly increased the activities of SOD, GSH-Px and CAT, while decreased the level of MDA in vivo and in vitro. Network pharmacology and molecular docking analyses revealed that the effects of DOE are mediated by oxidative stress-associated genes and the PI3K/Akt signaling pathway. The results of experiments showed that DOE regulated the PI3K/Akt/Nrf2/HO-1 signaling pathway, decreased protein expression level of phosphorylation PI3K (p-PI3K), phosphorylation Akt (p-Akt), Nrf2 and HO-1. Moreover, similar results were found for mRNA expression levels of PI3K, Akt, Nrf2 and HO-1 after DOE treatment.
DOE may exert anti-oxidative stress effects through PI3K/Akt/Nrf2/HO-1 signaling pathway,to improve aging-induced kidney injury.
铁皮石斛是传统中药中的一味主要药材，已被使用了数百年，因其滋阴、补肾和益胃生津的特性而闻名。近年来，现代药理学研究证实了其在抗衰老和肾脏保护方面的潜力，凸显了其在传统和现代背景下的治疗相关性。
本研究旨在探讨铁皮石斛改善衰老诱导的肾损伤的作用及其可能机制。
采用DPPH和ABTS自由基清除法评估铁皮石斛提取物（DOE）的抗氧化活性。建立D-半乳糖（D-gal）诱导的肾脏衰老模型和HO诱导的NRK-52E细胞模型，以评估DOE提取物在体外和体内的药效学。分别采用MTT法和β-半乳糖苷酶（SA-β-Gal）染色检测NRK-52E细胞的活力和衰老情况。通过苏木精-伊红染色、肾脏指数和血清肾毒性标志物分析来评估DOE的保护作用。在体内和体外评估活性氧（ROS）、超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）的浓度。利用网络药理学，我们确定了DOE的关键化学成分和潜在靶基因。为了验证这些靶点在相关途径中的功效，我们进行了分子对接研究，并结合蛋白质免疫印迹和实时定量PCR分析。
与HO组相比，DOE处理显著提高了NRK-52E细胞的活力，降低了SA-β-Gal阳性率。DOE显著改善了小鼠的一般状况，包括增加肾脏指数、降低尿蛋白浓度、血尿素氮（BUN）、肌酐含量（CRE）并改善肾脏组织损伤。此外，DOE处理在体内和体外均显著提高了SOD、GSH-Px和CAT的活性，同时降低了MDA水平。网络药理学和分子对接分析表明，DOE的作用是由氧化应激相关基因和PI3K/Akt信号通路介导的。实验结果表明，DOE调节PI3K/Akt/Nrf2/HO-1信号通路，降低磷酸化PI3K（p-PI3K）、磷酸化Akt（p-Akt）、Nrf2和HO-1的蛋白表达水平。此外，DOE处理后PI3K、Akt、Nrf2和HO-1的mRNA表达水平也有类似结果。
DOE可能通过PI3K/Akt/Nrf2/HO-1信号通路发挥抗氧化应激作用，从而改善衰老诱导的肾损伤。
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