A single chemosensor for multiple analytes: fluorogenic and ratiometric absorbance detection of Zn²⁺, Mg²⁺ and F⁻, and its cell imaging

A simple coumarin based sensor 1 has been synthesized from the condensation reaction of 7-hydroxycoumarin and ethylenediamine via the intermediate 7-hydroxy-8-aldehyde-coumarin. As a multiple analysis sensor, 1 can monitor Zn²⁺ with the fluorescence enhanced at 457 nm, and ratiometric detection at 290 nm, 350 nm and 420 nm in DMF/H₂O (1/4, v/v) medium. Sensor 1 can also monitor Mg²⁺ with the fluorescence enhanced at 430 nm, and ratiometric detection at 290 nm, 370 nm and 430 nm in DMF medium through the interaction of chelation enhance fluorescence (CHEF) with metal ions. Furthermore, 1 also can monitor F⁻ with the fluorescence enhanced at 460 nm, and ratiometric detection at 290 nm and 390 nm in DMF medium simultaneously via hydrogen bonding and deprotonation with F− anion. Spectral titration, isothermal titration calorimetry and mass spectrometry revealed that the sensor formed a 1:1 complex with Mg²⁺, Zn²⁺ or F⁻, with stability constants of 4.5 × 10⁶, 3.4 × 10⁶, 8.0 × 10⁴ M⁻1 respectively. The complexation of the ions by 1 was an exothermic reaction driven by entropy processes. Furthermore, the sensor exhibits good membrane-permeability and was capable of monitoring at the intracellular Zn²⁺ level in living cells

Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats

Diabetes mellitus (DM) is considered a risk factor for cognitive dysfunction. Harmine not only effectively improves the symptoms of DM but also provides neuroprotective effects in central nervous system diseases. However, whether harmine has an effect on diabetes-induced cognitive dysfunction and the underlying mechanisms remain unknown. In this study, the learning and memory abilities of rats were evaluated by the Morris water maze test. Changes in the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway were determined in both streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-treated SH-SY5Y cells by western blotting and histochemistry. Herein, we found that harmine administration significantly ameliorated learning and memory impairment in diabetic rats. Further study showed that harmine inhibited NLRP3 inflammasome activation, as demonstrated by reduced NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 levels, in the cortex of harmine-treated rats with DM. Harmine was observed to have similar beneficial effects in HG-treated neuronal cells. Moreover, we found that harmine treatment enhanced BDNF and phosphorylated TrkB levels in both the cortex of STZ-induced diabetic rats and HG-treated cells. These data indicate that harmine mitigates cognitive impairment by inhibiting NLRP3 inflammasome activation and enhancing the BDNF/TrkB signaling pathway. Thus, our findings suggest that harmine is a potential therapeutic drug for diabetes-induced cognitive dysfunction