Probucol mitigates high-fat diet-induced cognitive and social impairments by regulating brain redox and insulin resistance.

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.

Water-Soluble High-Quality Ag2Te Quantum Dots Prepared by Mutual Adaptation of Synthesis and Surface Modification for In Vivo Imaging.

Near-infrared (NIR) in vivo fluorescence imaging has exhibited the distinct advantage of high optical resolution at deeper penetration into biological tissues. Ag2Te quantum dots (QDs), with a relatively narrow band gap, show great promise for fluorescence emission at long wavelengths in the second near-infrared (NIR-II) window for bioimaging. However, existing Ag2Te QDs have severely hindered the application of in vivo bioimaging due to their poor fluorescence brightness and stability, so it is important to prepare Ag2Te QDs with high quantum yield and stability as well as high biocompatibility in the NIR-II window. Herein, we designed an integrated method for the preparation of water-soluble Ag2Te QDs by mutual adaptation of QD synthesis and surface modification. We first synthesized high-quality Ag2Te QDs with different NIR-II emission wavelengths and the photoluminescence quantum yields (PLQYs) up to 6.51% by rapidly injecting the TBP-Te precursor into a hot solvent to form a highly fluorescent Ag2Te core. Then water-dispersible Ag2Te QDs were obtained by direct exchange of the hydrophobic Ag2Te QD surface ligands with thiol ligands. The PLQY of the water-soluble Ag2Te QDs obtained by this method can still be maintained at 4.94%. With these highly bright and stable Ag2Te QDs, the abdominal vessels, hindlimb arterial vessels, venous vessels, sacral lymph nodes, and tumor vessels were visualized non-invasively in vivo in the NIR-II window in mice. The results demonstrate that the integrated strategy of QD synthesis and modification provides valuable technical support for further in-depth applications of Ag2Te QDs.

Structural characterization, antiproliferative and anti-inflammatory activities of alkaloids from the roots of Zanthoxylum austrosinense.

Three new carbazole alkaloids, zanthoaustrones A-C (1-3), as well as nine known compounds 4-12, were isolated and characterized from the roots of Zanthoxylum austrosinense Huang (Rutaceae). Their chemical structures were elucidated on the basis of extensive and comprehensive spectroscopic methods, while the known alkaloids were identified by the comparison of their observed spectroscopic data including NMR data, MS data and optical rotation values with the data described in the literature. Furthermore, the antiproliferative activities as well as the anti-inflammatory effects of all isolated alkaloids in vitro were evaluated. All obtained alkaloids 1-12 displayed notable antiproliferative activities against diverse human cancer cell lines exhibiting IC50 values in range of 0.85 ± 0.06 to 29.56 ± 0.17 µM, which is equivalent to the positive control (cisplatin) showing IC50 values ranging from 1.58 ± 0.09 to 28.69 ± 0.21 µM. Moreover, compounds 1-12 exhibited pronounced inhibitory activities on nitric oxide (NO) production with IC50 values displaying IC50 values in range of 0.89 ± 0.05 to 9.62 ± 0.15 µM, which is comparable to the positive control (hydrocortisone) holding an IC50 value of 4.06 ± 0.11 µM. These findings indicate that the separation and characterization of these alkaloids displaying significant antiproliferative activities together with anti-inflammatory effects from the roots of Z. austrosinense could be meaningful to the research and development of new anti-cancer drugs as well as anti-inflammatory agents.