Nrf2 activator corosolic acid meliorates alloxan induced diabetic nephropathy in mice

Objective: To determine whether corosolic acid(CA) targeting nuclear protein expression of Nrf2 activation can be used to attenuate renal damage and preserve renal function in alloxan diabetic mice.Methods: A mouse model with diabetic nephropathy was established to examine the Nrf2 expression. Mice were randomly divided into control, diabetic control, and CA groups treated at 0.4 mg/kg, 2 mg/kg and 10 mg/kg p.o. for 8 weeks. Diabetes was induced in mice by single intraperitoneal injection of alloxan 200 mg/kg in all groups except the control. The mice with fasting blood glucose level over 200 mg/d L were considered as diabetic and were employed in the study. After 4 th and 8 th weeks, urine samples were collected(using metabolic cages) to measure protein and urea. Animals were euthanized, and serum samples were collected to estimate the glucose, creatinine, total protein, urea and blood urea nitrogen. Kidney was isolated at the end of experiment for histology to evaluate anti-oxidant parameters. Immunohistochemistry was performed to examine the Nrf2 expression.Results: CA treatment showed dose dependent reduction in level of biochemical parameters in serum and urine. CA group(10 mg/kg) showed significantly higher body weight and reduced kidney weight. Histopathological examination revealed reduced inflammation, collagen deposition and glomerulosclerosis in renal tissue. CA attenuated renal dysfunction, oxidative stress and inflammatory pro-cytokine levels.Conclusions: CA treatment exhibited ameliorative effect on kidney in mice with its enhanced Nrf2 expression.

A review of structural modification and biological activities of oleanolic acid

Oleanolic acid(OA),a pentacyclic triterpenoid,exhibits a broad spectrum of biological activities,including antitumor,antiviral,antibacterial,anti-inflammatory,hepatoprotective,hypoglycemic,and hypolipidemic effects.Since its initial isolation and identification,numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives.Despite this,there has been a dearth of comprehensive reviews in the past two decades,leading to challenges in subsequent research on OA.Based on the main biological activities of OA,this paper comprehensively summarized the modification strategies and structureactivity relationships(SARs)of OA and its derivatives to provide valuable reference for future investigations into OA.

Design,synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells

Ursolic acid(UA)is a naturally occurring ursane triterpenoid,which exhibits a wide range of unique biological activities.To clarify its mechanism of action(MOA),a series of fluorescent derivatives of UA(5a-c)were designed and synthesized by conjugation with 7-nitrobenzo-2-oxa-1,3-diazole(NBD)fluorophore.Among them,5c exhibited similar anti-proliferative activity with UA against HCT116 cells(half maximal inhibitory concentration(IC_(50))=9.21±0.50μmol/L).Cell imaging experiment indicated that 5c was rapidly taken up in HCT116 cells in a dose and time-dependent manner.Then,5c was found to localize in endoplasmic reticulum(ER),lysosomes,and mitochondria,but not in nucleus of HCT116 cells by confocal microscopy studies.Preliminary MOA proved that UA induced autophagy with a unique intracellular distribution mechanism involving ER and lysosome.In all,our work provides new clues for revealing the molecular mechanism of UA as an antitumor agent.