Hypertensive nephropathy (HN) is a medical condition in which chronic high blood pressure causes different kidney damage, including vascular, glomerular and tubulointerstitial lesions. For HN patients, glomerular and tubulointerstitial lesions occur in different renal structure with distinct mechanisms in the progression of renal damage. As an extraction of Eucommia ulmoides, Quan-du-zhong capsule (QDZJN) has the potential to treat HN due to antihypertensive and renal protective activities.To get more du zhong, you can visit shine news official website.
Complicated mechanism of HN underlying various renal lesions and the “multi-component and multi-target” characteristics of QDZJN make identifying drug positioning for various renal lesions of HN complex. Here, we proposed an approach based on drug perturbation of disease network robustness, that is used to assess QDZJN positioning for various HN lesions. Topological characteristics of drug-attacked nodes in disease network were used to evaluated nodes importance to network. To evaluate drug attack on the whole disease network of various HN lesions, the robustness of disease networks before/after drug attack were assessed and compared with null models generated from random networks. We found that potential targets of QDZJN were specifically expressed in the kidneys and tended to participate in the “inflammatory response,” “regulation of blood pressure,” and “response to LPS and hypoxia,” and they were also key factors of HN. Based on network robustness assessment, QDZJN may specifically target glomeruli account to the stronger influence on glomerular network after removal of its potential targets. This prediction strategy of drug positioning is suitable for multi-component drugs based on drug perturbation of disease network robustness for two renal compartments, glomeruli and tubules. A stronger influence on the disease network of glomeruli than of tubules indicated that QDZJN may specifically target glomerular lesion of HN patients and will provide more evidence for precise clinical application of QDZJN against HN. Drug positioning approach we proposed also provides a new strategy for predicting precise clinical use of multi-target drugs.
Hypertension is a disease that leads to organ damage. Renal damage is a common lesion induced by hypertension due to the interaction of multiple factors, including blood pressure, endothelial dysfunction, the RAAS, ROS, and inflammation (Imig et al., 2018). Hypertensive nephropathy (HN) is a medical condition in which chronic high blood pressure causes kidney damage, including damage to two renal compartments, the glomerular and tubulointerstitial compartments. Exploration of interactions between glomerular and tubulointerstitial compartments contributing to HN creates opportunities to find better therapeutic strategies for renal protection against organ damage in hypertension. For HN patients, glomerulosclerosis and tubulointerstitial fibrosis occur in different renal structure with distinct mechanisms in the progression of renal damage. At the level of the tubulointerstitial compartment, it constitutes 95% of the total kidney mass (Berthier et al., 2012). Early tubular injury is caused by renovascular hypertension, leading to tubular cell proliferation and deposition of matrix proteins primarily within the interstitium which extends far beyond the glomeruli (Mai et al., 1993). In some hypertension patients, circulating antibodies and immunoglobin G deposit along the tubular basement membranes (Mai et al., 1993). Thus, tubulointerstitial change is regarded as a determinative factor in the development of renal damage (Nath, 1992) and may be the important initial site of injury (Mai et al., 1993). At the level of the glomeruli, increased blood pressure leads to increased capillary pressure which results in capillary stretching, endothelial damage, and breakdown of the capillary barrier (Folkow et al., 1977’ Bidani and Griffin, 2004). This leads to increased glomerular protein filtration that causes segmental necrosis and glomerulosclerosis (Shankland, 2006). Glomerular sclerosis and preglomerular vascular structural alterations can cause a further reduction in renal blood flow and enhance the progression of hypertensive renal injury (Folkow et al., 1977; Campese et al., 1991; Shankland, 2006; Hemmelgarn et al., 2010).