Abstract
Corydalis humosa Migo is a traditional Chinese medicine that clears away damp heat, relieves sore. Protopine (PRO) is an alkaloid component isolated from C. humosa Migo. However, the role of protopine in acute kidney injury (AKI) has not yet been reported. This study aims to investigate the effect and mechanism of protopine isolated from C. humosa Migo on lipopolysaccharide (LPS)-induced AKI in mice. Inflammation accumulation was assessed by small animal living imaging. The blood urea nitrogen (BUN), and serum creatinine (Scr) were measured to assess the effects of protopine on renal function in LPS-induced AKI. The levels of tumor necrosis factor (TNF), interleukin-2 (IL-2), interferon-γ (IFN-γ), and (interleukin-10) IL-10 in serum were detected by cytometric bead array. Flow cytometry was used to detect the levels of reactive oxygen species (ROS) in primary kidney cells. The proportions of granulocytes, neutrophils, and macrophages in peripheral blood were examined to evaluate the effect of protopine on immune cells in mice with AKI. Toll-like receptor (TLR4) and apoptotic signaling pathway were detected by Western blot analysis. The results showed that protopine markedly improved the renal function, relieve inflammation, reversed inflammatory cytokines, transformed apoptosis markers, and regulated the TLR4 signaling pathway in mice with AKI induced by LPS. The protopine isolated from C. humosa Migo protected mice against LPS-induced AKI by inhibiting apoptosis and inflammation via the TLR4 signaling pathway, thus providing a molecular basis for a novel medical treatment of AKI.
Highlights
The essence of sepsis is systemic inflammatory reactions
In the 1H detected heteronuclear multiple bond correlation (HMBC) spectrum, δ6.79 had a cross peak with δ30.4 (C-5) and δ6.66 had a cross peak with δ46.6 (C-13), suggesting that H-4 was adjacent to C-5 and H-12 was adjacent to C-13; δ6.94 had a cross peak with δ194.6 (C-14), suggesting that H-1 was adjacent to C-14; δ5.95 had a cross peak with δ145.7 (C-9) and δ145.1 (C-10), suggesting that methylenedioxy was attached to C-9 and C-10; δ5.98 had a cross peak with δ147.2 (C-2) and 145.2 (C-3), suggesting that methylenedioxy was attached to C-2 and C-3; δ1.81 had a cross peak with δ50.6 (C-8) and 57.3 (C-6), suggesting that both C-6 and C-8 were connected to N
3, the results revealed lipopolysaccharide; Acute kidney injury (AKI): acute kidney serum blood urea nitrogen; H&E: that the levels of ROSand increased hematoxylin eosin). in mice with LPS-induced AKI, which could be reduced by protopine
Summary
The essence of sepsis is systemic inflammatory reactions. Multiple inflammatory mediators and enzymes participate in organism damage; the kidney is the most sensitive organ in sepsis infection [1]. Acute kidney injury (AKI) is a clinical syndrome caused by a variety of pathogens, leading to morbidity and mortality in patients [2]. The pathogenesis is complicated, including pro-inflammatory cytokines, ROS, and cell apoptosis [3,4,5]. Lipopolysaccharide (LPS)-induced sepsis remains the leading cause of AKI. One of the mechanisms of sepsis-induced AKI involves the release of bacterial endotoxins into the circulation, which activate interconnected inflammatory cascades in the kidney, leading to renal injury [6]. Because of the early excessive inflammatory response, T cells, B cells, and dendritic cells (DC) are severely depleted, Molecules 2020, 25, 15; doi:10.3390/molecules25010015 www.mdpi.com/journal/molecules
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