Background (20S)-Protopanaxatriol (PPT), a bioactive triterpenoid from Panax ginseng , has been used in Traditional Chinese Medicine (TCM) to tonify kidney yang and regulate blood pressure. The research aimed to elucidate PPT's protective effects against angiotensin II (Ang II)-induced renal injury. Methods A C57BL/6 mouse model of kidney injury was established by continuous infusion of Ang II for 4 weeks using an osmotic minipump. Treatment with PPT was initiated two weeks after Ang II infusion and administered daily for 14 days. Molecular docking, drug affinity response target stability (DARTS), and cellular thermal shift assay (CETSA) were employed to identify and validate potential targets of PPT in alleviating Ang II-induced renal injury. Additionally, biochemical assays, histopathological analysis, and Western blotting were performed to assess renal function, tissue damage, and signaling pathway modulation. Results Our findings demonstrated that PPT exerted protective effects against Ang II-induced renal dysfunction in mice by significantly attenuating renal fibrosis and inflammation. Mechanistically, PPT targeted PTPN1 and inhibited the AMPK/mTOR signaling pathway, thereby effectively alleviating autophagy dysregulation in both renal tissues of mice and Ang II-stimulated NRK-52E cells in vitro. Molecular docking, DARTS, and CETSA experiments confirmed PTPN1 as a direct target of PPT, providing a molecular basis for its renoprotective effects. Conclusion These findings validate ginseng's traditional use in kidney disorders and demonstrate PPT's potential as a therapeutic agent for hypertensive nephropathy by targeting PTPN1/AMPK/mTOR signaling. Further clinical exploration is needed to translate these results into practice.
Yong Wei,Yuye Xuan,Wenxiang Wang,Yonghui Zhang,Xiaoshan Li,Chunlan Liu,Chen Wang,Zhihai Liu
The existing screening methods for therapeutic targets of active ingredients in traditional Chinese medicine (TCM) have problems of long detection time and high instrument cost. This article proposes a new target screening method based on virtual screening and fiber surface plasmon resonance (SPR) sensing technology, which has the characteristics of flexibility, speed, and low cost. It also reveals the target mechanism of the active ingredient isoquercitrin in the treatment of insulin resistance (IR). The binding energies of isoquercitrin with target proteins PDPK1, INSR, and PTPN1 were calculated using computer virtual methods to be -8.9, -8.9, -8.8 kcal/mol, indicating strong binding activity with isoquercitrin and predicted as three key targets. Then a fiber optic SPR biosensor functionalized with isoquercitrin molecules was constructed to detect the binding affinity between isoquercitrin and the key targets. The experimental results showed that the binding affinities of isoquercitrin to the targets PDPK1, INSR, and PTPN1 were 1.45, 1.14, and 13.21, respectively, indicating that PTPN1 is the main target of isoquercitrin in the treatment of IR. The proposed sensor has a sensitivity of 0.699 nm/(μg/ml), LOD of 0.515μg/ml, and the experimental detection time of this method is as low as 45 minutes, without the need for large and expensive optical demodulation equipment, and the device volume is 5.50 dm3, providing new ideas for the screening of therapeutic targets of active ingredients in TCM.
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