β-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression

Abstract

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.

FBP1 induced by β‐elemene enhances the sensitivity of gefitinib in lung cancer

“…A recent study showed that FBP1 could directly bind to the transactivation domain and the domain containing the nuclear translocation signal of STAT3 to retain STAT3 in the cytoplasm 26 . Our results demonstrated that β‐elemene could reduce the expression level of p‐STAT3 in the nucleus via FBP1, which was consistent with previous studies 39,40 . Subsequent experiments showed that activation of STAT3 could attenuate the effects of β‐elemene on gefitinib‐resistant cells, which indicated that STAT3 was involved in β‐elemene function.…”

“… 26 Our results demonstrated that β‐elemene could reduce the expression level of p‐STAT3 in the nucleus via FBP1, which was consistent with previous studies. 39 , 40 Subsequent experiments showed that activation of STAT3 could attenuate the effects of β‐elemene on gefitinib‐resistant cells, which indicated that STAT3 was involved in β‐elemene function. Anti‐apoptosis is a feature of chemoresistance, and β‐elemene exerts anti‐proliferative and anti‐apoptosis effects on tumor growth and multidrug resistance.…”

The effects of elemene emulsion injection on rat fecal microbiota and metabolites: Evidence from metagenomic exploration and liquid chromatography-mass spectrometry

“…Before the experiment started, rats were fed adaptively for 1 week and had free access to water and food. Different EEI concentrations were selected based on previously published studies (Ma et al, 2021 ; Sun et al, 2022 ; Wu et al, 2022 ). For 14 days, L-EEI rats received elemene emulsion [20 mg/(kg·d)] intraperitoneally (IP), H-EEI rats received elemene emulsion [40 mg/(kg·d)] IP, and group S rats received the same volume of normal saline IP as H-EEI.…”

Chronic Kidney Disease Diets for Kidney Failure Prevention: Insights from the IL-11 Paradigm

“…A similar study was performed with β-elemene using the same mouse model of AKI and in vitro rat interstitial fibroblast cells stimulated by TGFβ. Treatment with β-elemene decreased the expression of fibrotic proteins and inhibited SMAD signaling [131]. 12 weeks.…”

“…The phytochemicals, such as allicin found in garlic, osthole (a coumarin derivative found in the Umbelliferae and Rutaceae families) [130], and a terpenoid β-elemene found in mint and celery [131], emerge as renoprotective due to their suppression of IL-11 and MAPK/ERK pathways in experimental models [132]. Allicin decreased albuminuria and renal fibrosis, accompanied by reduced expression of TGFβ1 and p-ERK1/2 in a rat model of STZ-induced diabetic nephropathy [132].…”