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Introduction
Diabetic nephropathy (DN) is a common complication of diabetes, characterized by abnormal angiogenesis of glomerular endothelial cells (GECs) and macrophage infiltration Galectin-3, a protein involved in the pathogenesis of DN, binds with its ligand, advanced glycation end products (AGEs), contributing to the progression of the disease However, recent research has shown promising results in the use of catalpol, an iridoid glucoside extracted from Rehmannia glutinosa, in ameliorating vascular inflammation and protecting against endothelial damage in diabetic environments This article aims to explore the potential of catalpol as an anti-angiogenic and anti-inflammatory agent in the context of AGEs-induced DN.
Understanding the Role of Galectin-3 in DN
Galectin-3 has emerged as a key player in the pathogenesis of DN. It is involved in various cellular processes, including cell proliferation, migration, and inflammation In the presence of AGEs, galectin-3 levels are elevated, leading to increased expression of pro-angiogenic factors such as vascular endothelial growth factor A (VEGFA) .These factors contribute to abnormal angiogenesis and endothelial dysfunction in DN .
Investigating the Effects of Catalpol on GECs and Macrophages
To determine the optimal concentration of AGEs and treatment time, mouse GECs (mGECs) and RAW 264.7 macrophages were treated with various concentrations of AGEs for different durations . The expression levels of galectin-3 and VEGFA were significantly higher in mGECs and macrophages treated with 50 µg/mL AGEs for 48 hours .
Catalpol and GB1107, a galectin-3 inhibitor, were shown to block the AGEs-induced proliferation of mGECs and macrophages . Interestingly, over-expression of galectin-3 reduced the inhibitory effect of catalpol on cell proliferation . This suggests that catalpol exerts its anti-angiogenic and anti-inflammatory effects, at least in part, through modulation of galectin-3 activity.
Targeting the HIF-1α/Galectin-3 Pathway
Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that plays a crucial role in angiogenesis . Catalpol was found to significantly decrease the expression of HIF-1α, VEGFR1, and VEGFR2 in mGECs exposed to AGEs . The inhibitory effect of catalpol on galectin-3 in AGEs-treated mGECs was impaired by PX-478, a HIF-1α inhibitor . These findings suggest that catalpol may disrupt the HIF-1α/galectin-3 pathway, thereby inhibiting angiogenesis in DN.
In Vivo Studies: The Effect of Catalpol on Diabetic Rats
To assess the potential therapeutic benefits of catalpol in DN, a rat model of the disease was established . Catalpol and GB1107 were administered intragastrically to diabetic rats for 12 weeks . The expression of galectin-3, VEGFR1, VEGFR2, and HIF-1α in the renal cortices of the rats was analyzed . Catalpol significantly inhibited the expression of galectin-3, macrophage infiltration, collagen accumulation, and angiogenesis in the kidneys of the diabetic rats .
Conclusion
Catalpol shows promise as a potential treatment for DN. Through its inhibitory effects on galectin-3 and the HIF-1α/galectin-3 pathway, catalpol can prevent abnormal angiogenesis of GECs and macrophage proliferation, ultimately preventing the progression of diabetes-induced renal damage . Further research is needed to fully understand the mechanisms by which catalpol exerts its effects and to explore its potential clinical applications in the treatment of DN.
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