Recently, a research team from Xinjiang Medical University published a study in Phytomedicine entitled “Unveiling the protective effects of Cistanche phenylethanol glycosides against D-galactose–induced kidney aging: Insights from network pharmacology and transcriptomics.” The study demonstrated that CPhGs exert protective effects against renal aging by modulating the STAT1, P53, and cGAS–STING signaling pathways. These effects are accompanied by reduced oxidative stress, apoptosis, and inflammation, as well as restoration of normal cell cycle progression.
Overall, the findings suggest that CPhGs hold therapeutic potential for the management of age-related kidney diseases and may represent a promising intervention strategy, providing mechanistic insights for future clinical applications.
Renal Aging and Experimental Design
The kidney, as an essential metabolic organ, is particularly vulnerable to age-related deterioration. With advancing age, the structural integrity of the kidney gradually declines, resulting in a marked reduction in renal function.
Cistanche deserticola is a well-recognized medicinal plant with anti-aging properties. Although the pharmacological significance of its active constituents, phenylethanol glycosides (CPhGs), has been well established, their potential protective effects against kidney aging and the associated molecular mechanisms have not been fully elucidated.
Recently, a research team from Xinjiang Medical University published an article in the journal Phytomedicine entitled “Unveiling the protective effects of Cistanche phenylethanol glycosides against D-galactose–induced kidney aging: Insights from network pharmacology and transcriptomics.”
The study revealed that CPhGs exert anti-aging effects on the kidney by regulating the STAT1, P53, and cGAS–STING signaling pathways. These regulatory effects contribute to the attenuation of oxidative stress, cellular apoptosis, and inflammation, while simultaneously restoring normal cell cycle progression.
In this study, mice were first divided into five groups: a control group (Ctrl), an aging model group (Model), a low-dose CPhGs group, a high-dose CPhGs group, and a vitamin E (VE) group. The control group received subcutaneous injections of normal saline and oral administration of saline, while all other groups were subcutaneously injected with D-galactose to induce aging and orally administered CPhGs or VE accordingly.
The results showed that, compared with the control group, the model group exhibited significantly elevated serum levels of creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA), and cystatin C (Cys-C), indicating severe renal dysfunction. Notably, treatment with CPhGs—particularly high-dose CPhGs (CPhGs-H)—significantly improved renal function.
Molecular Mechanisms Underlying the Anti-Aging Effects of CPhGs
In vitro experiments demonstrated that CPhGs significantly reduced reactive oxygen species (ROS) accumulation, improved mitochondrial function, and decreased markers of cellular senescence (CS). Integrated transcriptomic and network pharmacology analyses further revealed that the STAT1, P53, and cGAS–STING signaling pathways serve as key mediators of the anti-aging effects of CPhGs.
Subsequent experimental validation confirmed that CPhGs downregulated the protein expression of P53, P21, and P16, modulated the expression of apoptosis-related proteins Bax and Bcl-2, and inhibited the expression of STAT1, cGAS, STING, and NF-κB. These findings provide mechanistic insights into how CPhGs confer renal protection and exert anti-aging properties.
Conclusion
In summary, the results of this study indicate that CPhGs possess significant potential for the treatment of age-related kidney diseases. These findings highlight CPhGs as a promising intervention strategy and offer valuable mechanistic insights that may support their future clinical application.