Renal fibrosis is a chronic pathological process that seriously endangers human health. However, the current therapeutic options for this disease are extremely limited. Previous studies have shown that signaling factors such as JAK2/STAT3, Smad3, and Myd88 play a regulatory role in renal fibrosis, and β-elemene is a plant-derived sesquiterpenoid organic compound that has been shown to have anti-inflammatory, anti-cancer, and immunomodulatory effects. In the present study, the anti-fibrotic effect of β-elemene was demonstrated by in vivo and in vitro experiments. It was shown that β-elemene inhibited the synthesis of extracellular matrix-related proteins in unilateral ureteral obstruction mice, and TGF-β stimulated rat interstitial fibroblast cells, including α-smooth muscle actin, vimentin, and connective tissue growth factor, etc. Further experiments showed that β-elemene reduced the expression levels of the above-mentioned fibrosis-related proteins by blocking the phosphorylation of JAK2/STAT3, Smad3, and the expression or up-regulation of MyD88. Notably, knockdown of MyD88 attenuated the phosphorylation levels of STAT3 and Smad3 in TGF-β stimulated NRK49F cell, which may be a novel molecular mechanism by which β-elemene affects renal interstitial fibrosis. In conclusion, this study elucidated the anti-interstitial fibrosis effect of β-elemene, which provides a new direction for future research and development of drugs related to chronic kidney disease.

Ischemia‑reperfusion injury‑induced acute kidney injury (IRI‑AKI) involves inflammatory cell infiltration and increased apoptosis, although the potential association between these processes remains unclear. The aim of the present study was to assess the impact of β‑elemene treatment on the IRI‑AKI using both in vivo and in vitro models, reverse transcription‑quantitative PCR, western blot assays, hematoxylin and Eosin (H&E) staining, Immunohistochemical staining and TUNEL staining. β‑elemene significantly decreased morphological and pathological kidney inflammation in mice caused by IRI. Additionally, β‑elemene prevented the expression of inflammatory factors and apoptosis proteins dose‑dependently in IRI mice and rat renal proximal tubule NRK52E cells treated with H₂O₂. Mechanistically, β‑elemene exerted its effects by inhibiting toll‑like receptor 4/myeloid differentiation primary response gene 88 (MyD88) signal activation and blocking NF‑κB/MAPK signal phosphorylation. Additionally, the increases in apoptosis and MAPK signal activation following hydrogen peroxide treatment were restored by MyD88 inhibition in NRK52E cells. The present study revealed that β‑elemene is a promising preclinical candidate for AKI.

Renal ischemia–reperfusion (I/R) injury is an unavoidable complication associated with renal transplantation, and currently, there are no targeted therapeutic interventions. The objective of this study was to explore the molecular mechanisms that contribute to I/R‐induced acute kidney injury (I/R‐AKI) and to discover potential targets for effective renal safeguarding. Bioinformatics techniques were employed to analyse critical genes regulating I/R‐AKI at the single‐cell level and to develop diagnostic models. Additionally, key pharmacological agents that inhibit the expression of target genes were identified for subsequent experimental validation. Pathological changes in the kidneys of I/R mice and patients with AKI were observed using immunofluorescence, western blotting, immunohistochemistry and transmission electron microscopy. We developed and validated a robust diagnostic model for I/R‐AKI. The results suggest that ADAMTS1 acts as a promoter of renal I/R‐AKI. In I/R‐AKI, ADAMTS1 was significantly upregulated in renal tubular epithelial cells. Furthermore, apoptosis mediated by the mitochondrial pathway was a critical factor in the progression of renal I/R injury. In mouse models of I/R‐AKI, the inhibition of ADAMTS1 with troglitazone significantly reduced both functional and histological damage. The diagnostic model can serve as a valuable instrument for diagnosing I/R‐AKI. Furthermore, troglitazone can significantly contribute to managing I/R‐AKI by inhibiting the expression of ADAMTS1. This study provides critical insights that may inform future research on therapeutic targets for renal ischaemia–reperfusion injury.