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Shengxian decoction decreases doxorubicin?induced cardiac apoptosis by regulating the TREM1/NF??B signaling pathway.

ABSTRACT: Shengxian decoction (SXT) is a traditional Chinese medicine that is clinically used for treating cardiovascular diseases. It is known for its beneficial effect on cardiomyocyte injuries, some of which can be induced by anticancer agents including doxorubicin (DOX). To determine the molecular mechanisms involved in the cardioprotective effects of SXT, DOX?induced H9c2 cells were analyzed for apoptosis and expression levels of apoptosis biomarkers. Cell viability and apoptosis were measured by CCK?8 and flow cytometry. Triggering receptors expressed on myeloid cells 1 (TREM1), cleaved caspase?3, survivin and NF??Bp65 expression levels were measured by reverse transcription?quantitative PCR and/or western blotting. A total of 30 adult male Sprague?Dawley rats were randomly allocated into five groups (n=6 each); control group receiving 0.9% saline, 1 DOX group receiving 2.5 mg/kg of DOX and 3 DOX + SXT groups, receiving a DOX dose equivalent to the DOX?only group and either 0.4, 0.8 or 1.6 g/kg of SXT. It was found that DOX increased apoptosis and NF??B activation of H9c2 cells by increasing TREM1 expression and that SXT inhibited apoptosis and NF??B activation of H9c2 cells induced by DOX or Trem1 overexpression. SXT also significantly reversed DOX?induced cardiotoxicity in rats. The results suggested that the protective effects of SXT against DOX?induced apoptosis may be attributed to its downregulation of TREM1.

SUBMITTER: Yao L

PROVIDER: S-EPMC7845587 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Shengxian decoction decreases doxorubicin‑induced cardiac apoptosis by regulating the TREM1/NF‑κB signaling pathway.

Yao Lei L Gui Mingtai M Li Jianhua J Lu Bo B Wang Jing J Zhou Xunjie X Fu Deyu D

Molecular medicine reports 20210126 3

Shengxian decoction (SXT) is a traditional Chinese medicine that is clinically used for treating cardiovascular diseases. It is known for its beneficial effect on cardiomyocyte injuries, some of which can be induced by anticancer agents including doxorubicin (DOX). To determine the molecular mechanisms involved in the cardioprotective effects of SXT, DOX‑induced H9c2 cells were analyzed for apoptosis and expression levels of apoptosis biomarkers. Cell viability and apoptosis were measured by CCK ...[more]

PMID: 33495812

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Project description:BackgroundPolycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women. Rhamnocitrin (Rha) has anti-inflammatory and antioxidant actions. The WNT1-inducible-signaling pathway protein 2 (Wisp2) and nuclear factor (NF)-κB are involved in fibrosis in many diseases. We aimed to elucidate the role of Rha in fibrosis of PCOS and the underlying mechanisms.MethodsDehydroepiandrosterone (DHEA)-incubated ovarian granulosa KGN cells were treated by Rha. Cell proliferation was detected with cell counting kit-8 (CCK-8) and 5-ethynyul-2'-deoxyuridine (EdU) staining. The levels of Wisp2 and transforming growth factor-β1 (TGF-β1) in supernatant were measured by enzyme-linked immunosorbent assay (ELISA). We observed α-smooth muscle actin (α-SMA) protein by immunofluorescence (IF). The levels of fibrosis factors were determined using Western blot. We observed p65 nuclear translocation with confocal microscopy. We used Wisp2 overexpression and knockdown in cells treated with DHEA or Rha to validate Wisp2 function. Interaction between Wisp2 and NF-κB, as well as Wisp2 and PPARγ, were assessed by co-immunoprecipitation assay, luciferase reporter assay and chromatin immunoprecipitation (ChIP).ResultsThe results showed that Rha elevated the reduced proliferation of DHEA-treated cells. In addition, Rha reversed the decreased Wisp2 and the increased TGF-β1 in supernatant. The proteins CTGF, α-SMA, Collagen I, TGF-β1, p-Smad2, and p-Smad3 were up-regulated while Wisp2, Sirt1, and PPARγ were down-regulated by DHEA treatment, which were reversed by Rha. Meanwhile, DHEA up-regulated p-IKBa and p-p65 and promoted p65 nuclear translocation, which were inhibited by Rha. These effects of Rha were antagonized by Wisp2 knockdown and were mimicked by Wisp2 overexpression. We confirmed the protein interaction between Wisp2 and NF-κB, along with Wisp2 and PPARγ.ConclusionsWisp2-mediated PPARγ/NF-κB/TGF-β1/Smad2/3 signaling contributes to Rha-improved ovarian granulosa cells fibrosis, suggesting Rha as a novel agent for the treatment of PCOS.

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Shengxian decoction decreases doxorubicin?induced cardiac apoptosis by regulating the TREM1/NF??B signaling pathway.

Publications

Shengxian decoction decreases doxorubicin‑induced cardiac apoptosis by regulating the TREM1/NF‑κB signaling pathway.

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