Echinacoside (ECH) is a naturally occurring phenylethanoid glycoside, isolated from , and this study aimed to analyze its effect on thermogenesis and its interaction with dopaminergic receptors 1 and 5 (DRD1 and DRD5) in 3T3-L1 white adipocytes and mice models. We employed RT-PCR, immunoblot, immunofluorescence, a staining method, and an assay kit to determine its impact. ECH showed a substantial increase in browning signals in vitro and a decrease in adipogenic signals in vivo. Additionally, analysis of the iWAT showed that the key genes involved in beiging, mitochondrial biogenesis, and ATP-dependent thermogenesis were upregulated while adipogenesis and lipogenesis genes were downregulated. OXPHOS complexes, Ca signaling proteins as well as intracellular Ca levels were also upregulated in 3T3-L1 adipocytes following ECH treatment. This was collectively explained by mechanistic studies which showed that ECH mediated the beiging process the DRD1/5-cAMP-PKA and subsequent downstream molecules, whereas it co-mediated the α1-AR-signaling thermogenesis via the DRD1/5/SERCA2b/RyR2/CKmt pathway in 3T3-L1 adipocytes. Animal experiments revealed that there was a 12.28% reduction in body weight gain after the ECH treatment for six weeks. The effects of ECH treatment on adipose tissue can offer more insights into the treatment of obesity and metabolic syndrome.
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http://dx.doi.org/10.4014/jmb.2306.06041 | DOI Listing |
RSC Adv
January 2025
Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area (Ningxia Medical University), Ministry of Education, School of Pharmacy, Ningxia Medical University 1160 Shengli Street Yinchuan 750004 China
The Keap1 (Kelch-like ECH-Associating Protein 1)-Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2)-ARE (Antioxidant Response Element) signaling pathway plays a crucial role in the oxidative stress response and has been linked to the development and progression of various diseases. Its influence on cerebral ischemia/reperfusion (I/R) injury has garnered significant attention. In our study, we investigated the effect of compound 2, a non-covalent inhibitor of the Keap1-Nrf2 interaction, which was previously discovered by our research group.
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January 2025
Department of Spine Surgery, The Fifth Affiliated Hospital of Guangxi Medical University, 89 Qixing Road, Nanning, Guangxi, 530022, China.
Background: This study aimed to investigate the impact of AM1241 on lipopolysaccharide (LPS)-induced chondrocyte inflammation in mice and its potential mechanism for improving osteoarthritis (OA).
Methods: The OA mice model was established employing the refined Hulth method. The impact of different concentrations of AM1241 on mice chondrocyte activity was detected using CCK-8.
Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor regulating cellular redox homeostasis, exhibits a complex role in cancer biology. Genetic mutations in the Kelch-like ECH-associated protein 1 (KEAP1)/NRF2 system, which lead to NRF2 hyperactivation, are found in 20% to 30% of lung cancer cases. This review explores the intricate interplay between NRF2 and key oncogenic pathways in lung cancer, focusing on the interaction of KEAP1/NRF2 system with Kirsten rat sarcoma virus (KRAS), tumor protein P53 (TP53), epidermal growth factor receptor (EGFR), and phosphatidylinositol 3-kinases (PI3K)/AKT signaling.
View Article and Find Full Text PDFSci Rep
January 2025
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Antibody-drug conjugates (ADCs) are an emerging strategy in cancer therapy, enhancing precision and efficacy by linking targeted antibodies to potent cytotoxic agents. This study introduces a novel ADC that combines ribonuclease A (RNase A) with cetuximab (Cet), an anti-EGFR monoclonal antibody, through a polyethylene glycol (PEG) linker (RN-PEG-Cet), aimed to induce apoptosis in KRAS mutant colorectal cancer (CRC) via a ROS-mediated pathway. RN-PEG-Cet was successfully synthesized and characterized for its physicochemical properties, retaining full enzymatic activity in RNA degradation and high binding affinity to EGFR.
View Article and Find Full Text PDFBiofactors
January 2025
Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan, ROC.
Ultraviolet (UV) irradiation is a major factor contributing to skin photoaging, including the formation of reactive oxygen species (ROS), collagen breakdown, and overall skin damage. Insulin-like growth factor-I (IGF-1) is a polypeptide hormone that regulates dermal survival and collagen synthesis. Echinacoside (Ech), a natural phenylethanoid glycoside, is the most abundant active compound in Cistanches.
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