ETHNOPHARMACOLOGICAL RELEVANCE: 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.
AIM OF THE STUDY: This study aimed to investigate the impacts and possible mechanism of Dendrobium officinale in ameliorating aging-induced kidney injury.
MATERIALS AND METHODS: 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 HOinduced 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. 2 2
RESULTS: DOE treatment markedly increased the viability and reduced the SA-β-Gal-positive rate of NRK-52E cells as compared to the HOgroup. 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. 2 2
CONCLUSIONS: DOE may exert anti-oxidative stress effects through PI3K/Akt/Nrf2/HO-1 signaling pathway,to improve aging-induced kidney injury.
