Eleutherococcus senticosus Alleviates Aristolochic-Acid-Induced Acute Kidney Damage by Inhibiting the NLRP3/IL-1β Signaling Pathway in Mice

Abstract

Eleutherococcus senticosus (ES) exerts various pharmacological effects, including renoprotection in a rat model of renal ischemia-reperfusion injury. However, the mechanisms of these effects remain unclear. Therefore, we investigated the effects and mechanisms of ES on aristolochic acid (AA)-induced acute kidney injury in mice. The experimental mice were divided into the control group, the model group (AA-induced acute kidney injury model), the model + ES group (Eleutherococcus senticosus boiled-free granules treated by gavage for two weeks), the model + fasudil group (fasudil administered intraperitoneally for three days), and the model + ES + fasudil group. After AA intervention in normal mice, the expression of ASC and NLRP3 and the levels of IL-1β, IL-18, and TNF-α were significantly elevated in mouse renal tissues (P < 0.05). However, AA-induced renal dysfunction was ameliorated by both ES and fasudil, which was confirmed by the decrease in serum creatinine and blood urea nitrogen levels, as well as by renal histopathological abnormalities such as renal tubule dilation and tubular formation. In addition, the inflammatory response of AA-induced renal inflammation was inhibited by both ES and fasudil, and the expression of ASC and NLRP3 and the levels of IL-1β, IL-18, and TNF-α were significantly higher in mouse renal tissues after the treatment of either ES or fasudil (P < 0.05). ES may be a potential treatment agent for aristolochic-acid-triggered nephropathy, with inhibition of the NLRP3/IL-1β as one plausible underlying mechanism.

Keywords

acute kidney damage - Araliaceae - Eleutherococcus senticosus - fasudil - aristolochic acid nephropathy - inflammatory vesicles

• References

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