Renal ischemia reperfusion injury (RIRI) is one of the main causes of acute kidney injury (AKI), which can lead to acute renal failure. The development of RIRI is so complicated that it involves many factors such as inflammatory response, oxidative stress and cell apoptosis. Ganoderic acids (GAs), as one of the main pharmacological components of Ganoderma lucidum, have been reported to possess anti-inflammatory, antioxidant, and other pharmacological effects. The study is aimed to investigate the protective effect of GAs on RIRI and explore related underlying mechanisms. The mechanisms involved were assessed by a mouse RIRI model and a hypoxia/reoxygenation model. Compared with sham-operated group, renal dysfunction and morphological damages were relieved markedly in GAs-pretreatment group. GAs pretreatment could reduce the production of pro-inflammatory factors such as IL-6, COX-2 and iNOS induced by RIRI through inhibiting TLR4/MyD88/NF-kB signaling pathway. Furthermore, GAs reduced cell apoptosis via the decrease of the ratios of cleaved caspase-8 and cleaved caspase-3. The experimental results suggest that GAs prevent RIRI by alleviating tissue inflammation and apoptosis and might be developed as a candidate drug for preventing RIRI-induced AKI.

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterized by progressive enlargement of fluid-filled cysts derived from renal tubular epithelial cells, which has become the fourth leading cause of end-stage renal diseases. Currently, treatment options for ADPKD remain limited. The purpose of this study was to discover an effective therapeutic drug for ADPKD. With virtual screening, Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney-specific Pkd1 knockout mouse (PKD) model, we identified obacunone as a candidate compound for ADPKD drug discovery from a natural antioxidant compound library. In vitro experiments showed that obacunone significantly inhibited cyst formation and expansion of MDCK cysts and embryonic kidney cysts in a dose-dependent manner. In vivo, obacunone treatment significantly reduced the renal cyst development in PKD mice. Western blot and morphological analysis revealed that obacunone served as a NRF2 activator in ADPKD, which suppressed lipid peroxidation by up-regulating GPX4 and finally restrained excessive cell proliferation by down-regulating mTOR and MAPK signaling pathways. Experimental data demonstrated obacunone as an effective renal cyst inhibitor for ADPKD, indicating that obacunone might be developed into a therapeutic drug for ADPKD treatment.

Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary kidney disease, which is featured by progressively enlarged bilateral fluid-filled cysts. Enlarging cysts destroy the structure of nephrons, ultimately resulting in the loss of renal function. Eventually, ADPKD develops into end-stage renal disease (ESRD). Currently, there is no effective drug therapy that can be safely used clinically. Patients progressed into ESRD usually require hemodialysis and kidney transplant, which is a heavy burden on both patients and society. Therefore, looking for effective therapeutic drugs is important for treating ADPKD. In previous studies, herbal medicines showed their great effects in multiple diseases, such as cancer, diabetes and mental disorders, which also might play a role in ADPKD treatment. Currently, several studies have reported that the compounds from herbal medicines, such as triptolide, curcumin, ginkolide B, steviol, G. lucidum triterpenoids, Celastrol, saikosaponin-d, Sparganum stoloniferum Buch.-Ham and Cordyceps sinensis, contribute to the inhibition of the development of renal cysts and the progression of ADPKD, which function by similar or different mechanisms. These studies suggest that herbal medicines could be a promising type of drugs and can provide new inspiration for clinical therapeutic strategy for ADPKD. This review summarizes the pharmacological effects of the herbal medicines on ADPKD progression and their underlying mechanisms in both in vivo and in vitro ADPKD models.

Urea transporter (UT) proteins are a group of membrane proteins specifically facilitating the transmembrane transport of urea, primarily divided into the UT-A and UT-B subfamilies. Early studies have predominantly focused on their pivotal roles in the mechanism of urine concentration in kidneys. Recently accumulating evidences suggest that UTs are also expressed in the cardiovascular system, particularly in cardiomyocytes and vascular endothelial cells, where they contribute to critical physiological processes such as regulation of cell volume homeostasis, modulation of nitric oxide production, control of myocardial electrophysiological properties, and adaptation to cardiac stress. Importantly, impairments or disruptions in UT activities have been increasingly associated with the pathogenesis and progression of multiple cardiovascular disorders, including hypertension, uremic cardiomyopathy, myocardial hypertrophy, heart failure, cardiac conduction disorders and atherosclerosis, which deepens the understanding of the role of urea metabolism as a key component in cardiovascular homeostasis. This brief review summarizes the distribution and physiological functions of UTs in the cardiovascular system, and evaluates the potential and existing challenges of targeting UTs as a novel therapeutic approach for cardiovascular diseases.