Anti-renal amyloidosis potential of rosemary extract: A multidimensional mechanistic study

Abstract Objectives Amyloid protein buildup in the kidneys leads to renal amyloidosis (RA), which impairs kidney function and often progresses to end-stage renal disease. The underlying mechanisms are not fully understood, and effective treatments are lacking. Rosemary (Rosmarinus officinalis L.), an edible spice and medicinal herb, has demonstrated promising renal protective effects in recent years. Nevertheless, further investigation is needed to determine its effect on RA. Materials and methods A lysozyme amyloid-like fibril model (M-LYSO) was added to MES13 cell cultures or administered intravenously to C57BL/6 mice to mimic the pathological microenvironment of amyloidosis. Spectroscopic, histological, and molecular mechanistic analyses were performed to evaluate the modulatory effects of rosemary ethanol extract (REE) on RA using both in vitro and in vivo models. Results Spectroscopic analysis revealed that REE disrupted amyloid fibril structures and reduced the aggregation propensity of amyloid proteins. In vitro and in vivo studies have shown that REE alleviated cellular damage to MES13 cells by improving subcellular function. It restored calcium homeostasis and eliminated reactive oxygen species, which inhibited the PERK/ATF-4/CHOP endoplasmic reticulum stress pathway and the apoptosis pathway. Continuous oral administration of REE at doses of 100 and 200 mg/kg for 8 weeks significantly mitigated pathological changes in renal tissues and restored kidney function in the RA model. Conclusions These findings suggest that rosemary is a promising candidate for adjuvant therapy for RA.