Hyperglycemia augments formation of intracellular reactive oxygen species (ROS) with associated mitochondrial damage and increased risk of insulin resistance in type 2 diabetes. We examined whether quercetin could reverse chronic high glucose-induced oxidative stress and mitochondrial dysfunction. Following long-term high glucose treatment, complex I activity was significantly decreased in isolated mitochondria from HepG2 cells. Quercetin dose-dependently recovered complex I activity and lowered cellular ROS generation under both high and normal glucose conditions. Respirometry studies showed that quercetin could counteract the detrimental increase in inner mitochondrial membrane proton leakage resulting from high glucose while it increased oxidative respiration, despite a decrease in electron transfer system (ETS) capacity, and lower non-ETS oxygen consumption. A quercetin-stimulated increase in cellular NAD/NADH was evident within 2 h and a two-fold increase in PGC-1α mRNA within 6 h, in both normal and high glucose conditions. A similar pattern was also found for the mRNA expression of the repulsive guidance molecule b (RGMB) and its long non-coding RNA (lncRNA) RGMB-AS1 with quercetin, indicating a potential change of the glycolytic phenotype and suppression of aberrant cellular growth which is characteristic of the HepG2 cells. Direct effects of quercetin on PGC-1α activity were minimal, as quercetin only weakly enhanced PGC-1α binding to PPARα in vitro at higher concentrations. Our results suggest that quercetin may protect mitochondrial function from high glucose-induced stress by increasing cellular NAD/NADH and activation of PGC-1α-mediated pathways. Lower ROS in combination with improved complex I activity and ETS coupling efficiency under conditions of amplified oxidative stress could reinforce mitochondrial integrity and improve redox status, beneficial in certain metabolic diseases.
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http://dx.doi.org/10.1016/j.freeradbiomed.2018.09.037 | DOI Listing |
Pharmaceutics
January 2025
Programa de Pós-Graduação em Pesquisa Translacional em Fármacos e Medicamentos (PPG-PTFM), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, Brazil.
Amphotericin B (AmB) is a commonly utilized antifungal agent, which is also recommended for the treatment of certain neglected tropical diseases, including leishmaniasis. However, its clinical application is constrained because of its poor oral bioavailability and adverse effects, prompting the investigation of alternative drug delivery systems. Polymeric nanoparticles (PNPs) have gained attention as a potential drug delivery vehicle, providing advantages such as sustained release and enhanced bioavailability, and could have potential as AmB carriers.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
School of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Science, No. 6699 Qingdao Road, Jinan 250117, China.
: Rhamnetin 3--α-rhamnoside (ARR) is a major flavonoid of the herb Franch. & Sav., which has been used for treating liver diseases in China.
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January 2025
Innovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor, ranking fifth in terms of fatality with poor prognosis and a low survival rate. Rhoifolin (ROF), a flavonoid constituent, has previously been shown to suppress the proliferation of breast and pancreatic cancer cells. However, its inhibitory effect on HCC has remained unexplored.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
Institute of Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of the Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany.
Background/objectives: New drugs are required for the treatment of liver cancers and protozoal parasite infections. Analogs of the known anticancer active and antileishmanial 2',4',6'-trimethoxychalcone SU086 were prepared and investigated.
Methods: The chalcones were prepared according to the Claisen-Schmidt condensation protocol and analyzed.
Pharmaceuticals (Basel)
January 2025
Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal.
Background/objectives: Côa Valley, located in the northeast of Portugal, harbors more than 500 medicinal plant species. Among them, four species stand out due to their traditional uses: Desf. (hemorrhages, urethritis, hepatitis), L.
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