Lycopene (LYC) is a carotenoid, has antioxidant properties. This study investigated whether lycopene attenuates aristolochic acids (AAs) -induced chronic kidney disease. In this experiment, lycopene was used to intervene C57BL/6 mice with renal injury induced by aristolochic acid exposure. The histomorphological changes and serological parameters of the kidney were measured in order to assess the alleviating effect of lycopene on renal injury in aristolochic acid nephropathy. In vitro and in vivo experiments were carried out to verify the main mechanism of action and drug targets of lycopene in improving aristolochic acid nephropathy (AAN) and by various experimental methods such as ELISA, immunohistochemistry, immunofluorescence, Western-blot and qRT-PCR. The results showed that oxidative stress injury was induced in the kidney of mice after AAI exposure, resulting in inflammatory response and tubular epithelial cell apoptosis. The results showed that the Nrf2/HO-1 antioxidant signaling pathway was inhibited after AAI exposure. AAI induces oxidative stress injury in the kidney, which ultimately leads to inflammation and tubular epithelial cell apoptosis. After LYC intervened in the body, it activated Nrf2 nuclear translocation and its downstream HO-1 and NQO1 antioxidant signaling pathways. LYC inhibited ROS production by renal tubular epithelial cells, and alleviated mitochondrial damage. LYC further modulated the TNF-α/NF-κB signaling cascade, thereby reduced the accumulation of inflammatory factors in the renal interstitium. Moreover, LYC was able to up-regulate the expression of Bcl-2, down-regulate Bax expression and inhibit the activation of cleaved forms of Caspase-9 and Caspase-3, which finally attenuated the apoptosis of the mitochondrial pathway induced by AAI exposure. It was concluded that lycopene was able to activate the Nrf2 antioxidant signaling pathway to maintain the homeostasis of renal oxidative stress and ultimately attenuated renal inflammatory response and apoptosis. These results suggested that lycopene can be used as a drug to relieve AAN.

Previous studies have examined rotenone toxicity on the human central nervous system, especially in the pathogenesis of Parkinson’s disease, but few have investigated the effects of rotenone on the kidney. Here, rotenone-induced nephrotoxicity was evaluated by determining morphological, biochemical, oxidative stress-related, and apoptotic factor alterations in rat renal tissue. Morphological and biochemical analyzes showed that rotenone administration to rats damaged renal tissue. Western blot results revealed that rotenone-induced oxidative damage, causing overproduction of glutathione, malonaldehyde, and reactive oxygen species (ROS), and inhibiting superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. Rotenone also decreased the mitochondrial membrane potential and increased voltage-dependent anion channel (VDAC), caspase-3, and caspase-9 protein levels, indicating an association of apoptosis with renal damage. Our results suggest that glutathione, malonaldehyde, and ROS may be signals of rotenone-induced oxidative damage, and that the mitochondrial pathway plays a key role in apoptosis of renal cells following rotenone administration.

In recent years, plant-derived extracts are increasing interest from researchers worldwide due to good efficacy and lower side effects. Among the different plant extracts, Dracorhodin perchlorate (DP) is originated from Dragon's blood which has long been used as a natural medicine with various pharmacological activities. In the present study, we have explored the potential regulation of DP on fibroblast proliferation which promotes wound healing both in vitro and in vivo. DP at treatment of 12-24 h significantly induced fibroblast proliferation which is associated with increasing level of phosphorylated-extracellular signal-regulated kinase (ERK). Moreover, if ERK is halted with siRNA, DP cannot induce fibroblast proliferation. In vivo, DP ointment treatment at low- (2.5 μg/mL), medium- (5 μg/mL) and high-(10 μg/mL) doses, rat wounds healed more rapidly compared with the control group. After DP treatment for 7 days, Serpin family H member 1 (SERPINH1) staining confirmed enhanced fibroblast proliferation in the wound tissue. Finally, phosphorylated-ERK in the wound tissue remarkably increased with DP ointment treatment. Therefore, DP may be developed into a potential lead compounds for the treatment of wounds in clinical trials in the near future.

Aristolochic acid (AA) are persistent soil pollutants in the agricultural fields of the Balkan Peninsula. Preparations containing aristolochic acid are widely used for anti-inflammatory, diuretic, etc. To study the hepatotoxicity of aristolochic acid, 80 healthy SD rats were selected and divided into 20 mg/kg- AA group, 4 mg/kg-AA group, and 2 mg/kg-AA group and blank group, 20 rats per group. Mainly tested the body weight, liver function, liver tissue oxidative stress and pathological changes of liver tissue in rats. The ALT and AST activities in the serum of the rats in the administration groups were increased compared with the blank group. The activity of MDA in the administration groups was higher than that in the blank group; the activities of SOD, T-AOC and GSH-PX were significantly lower than those in the blank group. HE tissue sections also found that the administration groups showed varying degrees of hepatocyte boundary blur, nuclear fragmentation, and fibrosis tendency. Transmission electron microscopy showed that the mitochondria of the rat liver became more and more severely damaged with the increase of dose. Compared with the blank group, the mRNA expression of Bax, Caspase-9 and Caspase-3 in the administration groups were determined, while the mRNA expression of the Bcl-2 was increased. And compared with the blank control group, the expression levels of apoptotic proteins caspase-9 and caspase-3 increased significantly in the 20 mg/kg-AA group. Aristolochic acid can induce liver injury in rats through oxidative stress pathway and mitochondrial apoptosis pathway.