Cucurbitacin IIb improved active chromatin‐induced systemic lupus erythematosus via balancing the percentage of Th17 and Treg cells

Abstract

The pathogenesis of systemic lupus erythematosus (SLE) is closely associated with aberrant immune system. Here, the aim of our study was to explore the regulation of cucurbitacin IIb (CuIIb) to Th17/Treg cells in SLE. Compared with normal mice, the percentage of Treg cells was downregulated in SLE mouse model, and Th17 was upregulated. Meantime, the production of Treg‐related transcription factor (foxp3) in SLE model mouse was reduced, and the production of Th17‐related transcription factor (RORγt) was increased. After treatment with CuIIb, the percentage of Treg cells in SLE mice was partly upregulated, and Th17 cells percentage was downregulated. The expression of foxp3 and RORγt in SLE mice were promoted and inhibited by CuIIb treatment, respectively. SLE‐induced kidney injury also was improved by CuIIb treatment. In vitro, we demonstrated again that CuIIb upregulated the percentage of Treg cells in lymphocytes from SLE mice, and downregulated the percentage of Th17 cells. Highly expressed IL‐6 and IL17, and lowly expressed IL‐10 and TGF‐β in lymphocytes from SLE mice were repressed and facilitated by CuIIb treatment, respectively. Overall, our data proved that CuIIb improved kidney injury in SLE mice through balancing the percentage of Th17 and Treg cells. Our data provided a reliable evidence to support the potential of CuIIb in SLE treatment.

The effect of Boric Acid and Calcium Fructoborate on T Helper Cell Differentiation by Influencing Foxp3 and Ror-γt in Rheumatoid Arthritis and Systemic Lupus Erythematosus

“…In a study conducted in a lupus mouse model, the effect of Cucurbitacin IIb on Th17 and Treg cell percentages, Foxp3 and Ror-γt expression levels in cells isolated from the spleen of mice was investigated. As a result, it was observed that there was an increase in Treg cell population, decrease in Th17 cell population, increase in Foxp3 expression, decrease in Ror-γt expression, increase in IL-10 and TGF-β expression, and decrease in IL-17 and IL-6 levels in Cucurbitacin IIb applied groups compared to control [25].…”

“…Oxidative stress and metabolic abnormalities have been found to related to the imbalance of Treg and Th17 in SLE [23,24]. In a SLE mice model Cucurbitacin IIb, an substrate extracted from a traditional Chinese medicine, found to be improved kidney injury by balancing the Treg(CD4 + Foxp3 + ) /Th17(CD4 + IL-17A + ) percentage in the meanwhile upregulated Foxp3 expression and downregulated Ror-γt expression in splenic lymphocytes [25]. Latest studies signify that attempts to reduce pathogenic Th17 cell population and increase Treg cell stability may provide promising therapeutic approaches in both SLE and RA treatment.…”

Add-on sirolimus for the treatment of mild or moderate systemic lupus erythematosus via T lymphocyte subsets balance

“…8 A large number of studies have shown that due to the decrease in number of Tregs and increase in number of Th17 cells, Treg/Th17 ratio decreases, which negatively correlates with SLE disease activity. [36][37][38] In this study, the number of Tregs in the patients was lower than that of healthy individuals, while the absolute value of Th17 cells was higher. Therefore, the Treg/Th17 ratio was also significantly lower compared with healthy individuals, and the Treg/Th17 balance was tilted towards Th17.…”

Cucurbitacin IIb attenuates cancer cachexia induced skeletal muscle atrophy by regulating the IL‐6/STAT3/FoxO signaling pathway

“…CuIIb elicits antiproliferative effects in cervical (Vidal‐Gutiérrez et al, 2022) and lung cancer cells (Torres‐Moreno et al, 2020). It also induces apoptosis and cell cycle arrest via STAT3 and ameliorates active chromatin‐induced systemic lupus erythematosus (Wu et al, 2021).…”