Scientific Reports
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2023
·Vol. 13
·期 1
·1-13
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IF 4.6
Li Shaocong,He Qi,Chen Baihao,Zeng Jiaxu,Dou Xiangyun,Pan Zhaofeng,Xiao Jiacong,Li Miao,Wang Fanchen,Chen Chuyi,Lin Yuewei,Wang Xintian,Wang Haibin,Chen Jianfa
Iron homeostasis plays an essential role in joint health, while iron overload can cause damage and death of cartilage cells. Cardamonin (CAR) is a substance found in the fruit of the chasteberry plant and has anti-inflammatory and anti-tumor activities. We first administered iron dextran (500 mg/kg) intraperitoneally to establish an iron overload mouse model and surgically induced osteoarthritis. The extent of OA and iron deposition were assessed using Micro-ct, Safranin-O/fast green staining, H&E staining, and Prussian Blue 10 weeks later. We administered primary chondrocytes with Ferric Ammonium Citrate (FAC) to evaluate the chondrocyte changes. Chondrocytes were identified in vitro by toluidine blue staining, and chondrocyte viability was evaluated by CCK-8. The rate of apoptosis was determined by Annexin V-FITC/PI assay. The mechanism of action of CAR was verified by adding the SIRT1 inhibitor EX527, and the expression of SIRT1 and MAPK signaling pathways was detected by Western blot. Iron overload also promoted chondrocyte apoptosis, a process that was reversed by CAR. In addition, CAR reduced NLRP3 inflammasome production via the SIRT1-MAPK pathway, and the SIRT1 inhibitor EX527 inhibited the treatment of OA by CAR.CAR inhibited cartilage degeneration induced by iron overload both in vivo and in vitro. Besides, our study showed that iron overload not only inhibited type II collagen expression but also induced MMP expression by catalyzing the generation of NLRP3 inflammasome. Our results suggest that CAR can treat KOA by promoting SIRT1 expression and inhibiting p38MAPK pathway expression to reduce the production of NLRP3 inflammasome vesicles.
研究领域:
医学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 10
·4905-4920
·
IF 6.1
Pengfei Fan,Huali Meng,Wenhao Hao,Yan Zheng,Hui Li,Zhiyue Zhang,Lei Du,Xin Guo,Dongliang Wang,Yunyan Wang,Hao Wu
Atherosclerosis (AS)-induced cardiovascular disease is a leading cause of death worldwide. To date, there is still a lack of effective approaches for AS intervention. Cardamonin (CAD) is a bioactive food component, but its effect on AS is unknown. In this work, CAD was investigated for its effect on AS using low-density lipoprotein receptor knockout mice and tumor necrosis factor-alpha (TNF-α)-stimulated endothelial cells (ECs). After a 12-week intervention, CAD was found to significantly prevent AS formation in the aortic root and aortic tree, reduce the necrotic core area, and inhibit aortic inflammation and oxidative stress. Moreover, CAD quenched TNF-α-provoked inflammation and oxidative stress in ECs. RNA-sequencing identified nuclear factor erythroid-2 related factor 2 (NFE2L2, NRF2)/heme oxidase 1 (HO1) signaling to be drastically activated by CAD. CAD is a known activator of the aryl hydrocarbon receptor (AHR) which is a transcription factor of the NFE2L2 gene. Surprisingly, AHR was not required for CAD's action on the activation of NRF2/HO1 signaling since AHR gene silencing did not reverse this effect. Furthermore, a molecular docking assay showed a strong binding potential of CAD to the Kelch domain of the Kelch-like ECH-associated protein 1 (KEAP1) which sequesters NRF2 in the cytoplasm. Both CAD and the Kelch domain inhibitor Ki696 promoted NRF2 nuclear translocation, whereas the combination of CAD and Ki696 did not yield a greater effect compared with either CAD or Ki696, confirming the interaction of CAD with the Kelch domain. This work provides an experimental basis for CAD as a novel and effective bioactive food component in future AS interventions.
研究领域:
心血管疾病
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药理学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Zhenyu Feng,Yiheng Yang,Wenjun Zheng,Jie Bai,Qiu-yue Lin,Yijin Yang,Ningning Zhang,Yun-long Xia,Yunpeng Xie
Background Atrial fibrillation is primarily driven by atrial remodeling. Cardamonin, extracted from ancient Chinese remedies, has a beneficial effect on heart health. However, it is still needed to investigate the specific effects of Cardamonin on atrial remodeling. Methods We utilized Ang II to induce atrial fibrillation. Different doses of Cardamonin were administered to mice. AAV9-cTNT-USP18 and myocardial-specific knockout of USP18 were constructed. Through echocardiography, electrical stimulation, qPCR and pathological staining, the roles of CAR and USP18 in atrial remodeling were demonstrated. amiodarone was the positive control for observing the anti- atrial fibrillation effects of CAR. The indirect relationship between CAR and USP18 was found by various molecular biology experiments Results The findings indicated that Cardamonin effectively decreased the occurrence and duration of AF induced by Ang II, as well as lowered levels of atrial fibrosis, inflammation, and oxidative stress. Overexpression of USP18 could promote the inhibitory effect of Cardamonin on Ang II-induced incidence and duration of AF, and significantly suppressing atrial remodeling in mice. In contrast, knockout of USP18 significantly interfered with the anti-atrial remodeling effect of Cardamonin, increasing atrial remodeling. The anti-remodeling effect of CAR on the atrium is comparable to that of amiodarone. At the same time, it was found that CAR may bind to NRF2 to regulate the transcription level of USP18. USP18 may interact with SERCA2. Conclusions These results not only clarify that Cardamonin regulates atrial remodeling through USP18, but also provide a theoretical basis for the development of new and safe therapeutic drugs for atrial remodeling, opening up new avenues for the treatment of cardiovascular diseases and bringing hope for more effective and safer treatment options.
研究领域:
心脏病学
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分子生物学
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药理学
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心血管研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Yang Lu,Juan Liu,Anqi Tong,Yongling Lu,Lishuang Lv
People are at high risk of exposure to endogenous and exogenous acrolein (ACR). ACR can cause a multitude of illnesses, including cardiovascular disease, Alzheimer’s disease, and diabetes. In this study, we investigated the reaction pathway of cardamonin (CAR) or alpinetin (ALP) with ACR and the interconversion of CAR and ALP in vitro at 37 °C in phosphate-buffered saline using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Subsequently, ACR adducts of CAR, ALP, and their metabolites, for example, CAR-ACR-1, ALP-ACR, mono-ACR-pinocembrin chalcone (PIN-ACR), and mono- and di-ACR-naringenin (NAR-ACR and NAR-2ACR), were detected in urine samples, but only CAR-ACR-1 and ALP-ACR were detected in fecal samples from the CAR- and ALP-treated mouse groups using ultraperformance liquid chromatography–MS/MS, respectively. Quantitative analyses showed that CAR, ALP, and their metabolites markedly scavenged ACR in a dose-dependent manner in vivo. Furthermore, we also found that the metabolites of CAR or ALP remained and promoted the ACR-trapping ability.
研究领域:
药理学
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毒理学
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分析化学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
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