Lysimachia christinae Hance aqueous extract ameliorates renal injury in kidney stone rats and calcium oxalate crystal-induced oxidative stress in HK-2 cells via inhibiting the PI3K/Akt/mTOR pathway

Objectives: Kidney stones are a frequent urinary system disorder. Lysimachia christinae Hance is an accepted herb in traditional Chinese medicine for treating kidney stones. However, the effects and mechanisms of Lysimachia christinae Hance aqueous extract (LCH) are yet to be elucidated.

Methods: The function of the aqueous extract of LCH was assessed using kidney stone rat models induced by 1% ethylene glycol+2% NH4Cl. Additionally, an in vitro model of human renal tubular epithelial cells (HK-2) treated with calcium oxalate was used.

Results: Resultantly, the treatment of aqueous extract of LCH at different concentrations or LCH+LY294002 (PI3K-specific inhibitor) showed significant improvement in inorganic ions and renal pathological injury in nephrolithiasis rats. Besides, consistent with the in vivo assay, LCH-containing serum increased cell viability and inhibited oxidative stress and deposition of CA²⁺ in HK-2 cells, while the influences of LCH-containing serum were attenuated. Mechanistically, the aqueous extract of LCH and LCH-containing serum also promoted Nrf2 and HO-1 levels and inhibited the phosphorylated expression levels of PI3K, Akt, and mTOR.

Conclusion: This study shows that LCH ameliorates the kidney damage in kidney stone rats and HK-2 cells. The mechanism of LCH in treating kidney stones is related to the activation of the Nrf2/HO-1 axis and the inhibition of the PI3K/Akt/mTOR pathway.