Abstract
Diabetic nephropathy (DN) is characterized by inflammatory responses and extracellular matrix (ECM) accumulation. Astilbin is an active natural compound and possesses anti-inflammatory activity. The aim of this study was to evaluate the anti-inflammatory effect of astilbin on high glucose (HG)-induced glomerular mesangial cells and the potential mechanisms. The results showed that HG induced cell proliferation of HBZY-1 cells in a time-dependent manner, and astilbin inhibited HG-induced cell proliferation. The expression and secretion of inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), and ECM components, including collagen IV (Col IV) and fibronectin (FN), were induced by HG. Moreover, TGF-β1 and CTGF were also induced by HG. The induction by HG on inflammatory response and ECM accumulation was inhibited after astilbin treatment. Astilbin treatment also attenuated HG-induced decrease in expression of matrix metalloproteinase (MMP)-2 and MMP-9. The TLR4/MyD88/NF-κB pathway was activated by HG, and the inhibitor of TLR4 exhibited the same effect to astilbin on reversing the induction of HG. TLR4 overexpression attenuated the effect of astilbin on HG-induced inflammatory cytokine production and ECM accumulation. The results suggested that astilbin attenuated inflammation and ECM accumulation in HG-induced rat glomerular mesangial cells via inhibiting the TLR4/MyD88/NF-κB pathway. This work provided evidence that astilbin can be considered as a potential candidate for DN therapy.
Highlights
Diabetic nephropathy (DN) is a kind of kidney disease that affects approximately 25% of the patients with type 2 diabetes (Lytvyn et al, 2016; Tesch, 2017)
TLR4 overexpression resisted the effect of astilbin (Figures 8B–G). These findings suggested that TLR4 overexpression attenuated the effect of astilbin on high glucose (HG)-induced inflammatory cytokine production and extracellular matrix (ECM) accumulation
We found that HG induced proliferation of HBZY-1 cells, and astilbin attenuated the induction
Summary
Diabetic nephropathy (DN) is a kind of kidney disease that affects approximately 25% of the patients with type 2 diabetes (Lytvyn et al, 2016; Tesch, 2017). Astilbin Roles in DN of risk factors that promote the development and progression of DN, including long duration of diabetes, elevated glucose levels, high blood pressure, and dyslipidemia (Tziomalos and Athyros, 2015). Elevated glucose level is one of the main risk factors for the development and progression of DN (Tziomalos and Athyros, 2015). High blood sugar may lead to the formation of advanced glycation end products, which induces inflammation in the kidney and promotes the development of DN (Tziomalos and Athyros, 2015). Inhibiting inflammation and ECM accumulation is important for the management of DN
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