Loquat leaf polysaccharides improve glomerular injury in rats with anti-Thy 1 nephritis via peroxisome proliferator-activated receptor alpha pathway

Chronic glomerulonephritis frequently develops into renal failure that cannot be completely cured. Based on the success of anti-inflammatory Chinese herbs in treating chronic nephritis, our goal was to investigate the therapeutic effects and mechanism of action of loquat leaf polysaccharides (LLPS) on chronic anti-Thy-1 nephritis. A rat model of glomerulonephritis was used to study the effects of 8 weeks of enalapril or LLPS treatment. Twenty-four-hour rat urinary protein excretions were measured every week for 8 weeks. Then, all animals were sacrificed, renal-related biochemical parameters were analyzed, and histology and electron microscopy examinations of renal tissue samples were conducted. Renal cortex tissue was used to detect markers of renal fibrosis. RNA sequencing (RNA-seq) and in vitro experiments explored the signaling pathway involved in LLPS treatment effects. Compared with the disease control group, LLPS treatment significantly decreased the levels of serum creatinine and blood urea nitrogen, reduced urinary protein excretion, glomerular mesangial cell proliferation, and extracellular matrix hyperplasia, and attenuated the expression of proteins associated with podocyte injury and renal fibrosis. RNA-seq results showed that peroxisome proliferator-activated receptor (PPAR) is a potential signaling pathway involved in LLPS treatment of chronic glomerulonephritis. Increases in PPARα and plasminogen activator inhibitor-1 (PAI-1) caused by glomerulonephritis were inhibited by LLPS in vitro. Furthermore, when an agonist of PPARα (BMS-687453) was used to stimulate PPARα activity, LLPS treatment suppressed the expression of fibrosis factor PAI-1 partially via PPARα inhibition. These findings demonstrate that LLPS improved glomerular injury in rats with anti-Thy 1 nephritis via the PPARα pathway.