Nephroprotective effects of Amomum kravanh essential oil by inhibition of ferroptosis regulated by Nrf2/HO-1 signaling pathway.

BACKGROUND

Amomum kravanh Pierre ex Gagnep. (BDK) is a Zingiberaceae plant traditionally widely used as a sweet fragrance, and commonly also utilized in minority medicine for various kidney diseases, especially chronic kidney disease (CKD) in Tibetan and Mongolian medicine. However, the underlying mechanisms by which it confers renal protection remain to be fully clarified.

PURPOSE: To investigate the renal protective mechanism of which BDK's essential oil exerts in rats with CKD induced by adenine and 5/6 nephrectomy.

METHODS

Rat models of adenine and 5/6 nephrectomy chronic nephropathy were established, and the therapeutic effects were evaluated by detecting the blood biochemical levels and H&E-/Masson staining and fiber-related factors. Then, the chemical composition of BDK's essential oil and blood components were analyzed using GC-MS. The efficacy of eucalyptol was evaluated by adenine and 5/6 nephrectomy CKD model, with mechanistic studies conducted using RNA-seq, western blot, and metabolomic approaches.

RESULTS

The blood biochemical levels and histopathological analyses (H&E-/Masson's staining) revealed that the BDK's essential oil significantly enhanced renal function and ameliorated kidney tissue fibrosis. Furthermore, GC-MS analysis identified 33 components in the essential oil of BDK, with eucalyptol being the predominant chemical component at 74.07 %. Eucalyptol is capable of entering the bloodstream in its prototypical form. Then, the efficacy and mechanism of eucalyptol were confirmed by adenine/5/6 nephrectomy CKD models, and based on RNA-seq analysis, we found that eucalyptol could significantly improve kidney function and fibrosis of kidney tissues by blocking TGF-β/smad and NF-κB pathways and inhibit ferroptosis through the Nrf2/HO-1 signaling pathway.

CONCLUSION

Both BDK's essential oil and its main constituent, eucalyptol, exhibited protective effects against CKD. They both ameliorated oxidative stress, inflammation, and fibrosis in adenine/5/6 nephrectomy rats. Eucalyptol is implicated in ferroptosis and regulation of renal fibrosis via the Nrf2/HO-1 pathway.