OBJECTIVE To explore the mechanism of diabetes nephropathy regulated by essential oil from Fructus Alpiniae Zerumbet(EOFAZ) based on PINK1/Parkin/ferroptosis Signal.
METHODS Diabetes mellitus(DM) mice model was established by feeding high sugar and high fat diet(HFSD) and intraperitoneal injection of streptozotocin. The mice were given EOFAZ for intervention. Mice were randomly divided into normal group, DM group, DM+EOFAZ low dose group(90 mg·kg−1), DM+EOFAZ high dose group(180 mg·kg−1), DM+ferroptosis inhibitor group(Ferrostatin-1, 5 mg·kg−1), EOFAZ toxicity group(180 mg·kg−1). The DM + EOFAZ group and DM + Ferrostatin-1 group were given EOFAZ and Ferrostatin-1, respectively. At the same time, the normal group and DM group were given equal volume of physiological saline. The mice in each group were orally administered once a day for 8 weeks, and their blood were collected to measured fasting blood glucose. HE and PAS staining were used to observe the morphology of renal tissue; Western blotting was used to detecte the expression of mitochondrial autophagy key proteins PINK1 and Parkin. Western blotting and immunohistochemistry analysis were used to investigate the expression of ferroptosis marker proteins GPX4 and COX2. The iron assay kit was used to detect the iron content of the renal tissue. ELISA kit was used to analyze the levels of SOD, GSH, and MDA in renal tissue.
RESULTS Compared with DM group, EOFAZ could significantly ameliorate the renal histopathology changes, upregulate the expression of PINK1, Parkin, and GPX4, downregulate the expression of COX2, reduce iron content in renal tissue, increase SOD activity and GSH content, and reduce MDA levels. And there were no significant difference between the normal control group and EOFAZ toxicity group in those results.
CONCLUSION EOFAZ can ameliorate diabetes nephropathy, and its mechanism may be through regulating PINK1/Parkin/ ferroptosis signal.
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