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Tubulointerstitial fibrosis, a frequent complication of chronic kidney disease (CKD) is a major public health issue. Biochanin A (BCA), an isoflavone, has numerous pharmacological activities. However, its effect on renal fibrosis and underlying molecular mechanism has not yet been clarified. This study explored the effect of BCA on renal tubulointerstitial fibrosis and inflammation in mice. The mouse model of unilateral ureteral obstruction (UUO) in vivo and transforming growth factor (TGF)-β1 activated renal fibroblast (NRK 49F) cells in vitro model were used to assess the antifibrotic effect of BCA. Biochemical analysis, histopathology, western blotting, and immunofluorescent staining methods were performed to elucidate the mechanism of BCA. In vitro, BCA suppressed the expression of fibrogenic proteins in TGF-β1-activated renal fibroblasts. The treatment with BCA displayed less tubular injury, prevented the aberrant accumulation of extracellular matrix (ECM) components, and inhibited the TGF-β1/Smad2/3 signaling axis in the kidneys. Furthermore, BCA impeded the phosphorylation of NF-kB(p65) and blunted the expression of inflammatory genes in the obstructed kidneys. The UUO induced expressions of nod-like receptor protein 3 (NLRP3), active caspase 1, interleukin(IL)-18, and IL-1β proteins were decreased in the BCA treated groups. We also found the increased expression of redox-sensitive nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) proteins in BCA treated groups compared to the UUO control. These findings indicate that BCA has a therapeutic benefit against renal fibrosis, and the ameliorative effect is mediated via inhibiting the TGF-β1/Smad2/3 and NF-kB/NLRP3 signaling axis. [Display omitted] [ABSTRACT FROM AUTHOR]

Pathological cardiac hypertrophy is a characteristic feature in many cardiovascular diseases (CVDs). Aloin is an anthraquinone glycoside from Aloe species, and the effect of aloin on cardiac hypertrophy and associated fibrotic changes have not been elucidated. This study investigated the effect of aloin against the isoproterenol (ISO)-induced cardiac hypertrophy in rats. Cardiac hypertrophy experimental model was induced in rats by subcutaneous injection of ISO for 14 days. Meanwhile, the animals were administered orally with aloin at doses of 25 and 50 mg/kg/day. On the 15th day, cardiac echocardiography was performed, the heart was collected and subjected for histopathological, gene expression, and immunoblot studies. Additionally, the effect of aloin on ISO-induced hypertrophic changes in H9c2 cells was investigated. Aloin markedly alleviated ISO-induced heart injury, reduced cardiac hypertrophy, improved cardiac function, and histological alterations in the heart. Mechanistically, aloin attenuated ISO-induced fibrosis via inhibition of the levels of collagen I, α-smooth muscle actin (α-SMA), fibronectin, transforming growth factor-β (TGF-β) and pSmad2/3 proteins in the heart. Aloin alleviated ISO-induced myocardial oxidative damage and up-regulated the levels of antioxidant transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins. Moreover, aloin treatment attenuated ISO-induced hypertrophic changes and the generation of reactive oxygen species (ROS) in H9c2 cells in vitro. Our findings demonstrated that aloin alleviated ISO-induced cardiac hypertrophy and fibrosis via inhibiting TGF-β/pSmad2/3 signaling and restoring myocardial antioxidants, and therefore has promising therapeutic potential against cardiac hypertrophy and fibrosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a progressive renal complication which significantly affects the patient's life with huge economic burden. Untreated acute kidney injury eventually progresses to a chronic form and end-stage renal disease. Although significant breakthroughs have been made in recent years, there are still no effective pharmacological therapies for the treatment of acute kidney injury. Toll-like receptor 4 (TLR4) is a well-characterized pattern recognition receptor, and increasing evidence has shown that TLR4 mediated inflammatory response plays a pivotal role in the pathogenesis of acute kidney injury. The expression of TLR4 has been seen in resident renal cells, including podocytes, mesangial cells, tubular epithelial cells and endothelial cells. Activation of TLR4 signaling regulates the transcription of numerous pro-inflammatory cytokines and chemokines, resulting in renal inflammation. Therefore, targeting TLR4 and its downstream effectors could serve as an effective therapeutic intervention to prevent renal inflammation and subsequent kidney damage. For the first time, this review summarizes the literature on acute kidney injury from the perspective of TLR4 from year 2010 to 2020. In the current review, the role of TLR4 signaling pathway in AKI with preclinical evidence is discussed. Furthermore, we have highlighted several compounds of natural and synthetic origin, which have the potential to avert the renal TLR4 signaling in preclinical AKI models and have shown protection against AKI. This scientific review provides new ideas for targeting TLR4 in the treatment of AKI and provides strategies for the drug development against AKI. Unlabelled Image [ABSTRACT FROM AUTHOR]