Butylphthalide improves brain damage induced by renal ischemia-reperfusion injury rats through Nrf2/HO-1 and NOD2/MAPK/NF-κB pathways

Renal ischemia-reperfusion (I/R) injury leads to irreversible brain damage with serious consequences. Activation of oxidative stress and release of inflammatory mediators are considered potential pathological mechanisms. Butylphthalide (NBP) has anti-inflammatory and antioxidant effects on I/R injuries. However, it is unclear whether NBP can effectively mitigate renal I/R secondary to brain injury as well as its mechanism, which are the aims of this study. Both renal I/R injury rats and oxygen and glucose deprivation cell models were established and pre-intervened NBP. The Morris water maze assay was used to detect behavior. Hippocampal histopathology and function were examined after renal I/R. Apoptosis and tube-forming capacity of brain microvascular endothelial cells (BMVECs) were tested. Immunohistochemistry and Western blot were used to measure protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway and NOD-like receptor C2 (NOD2)/Mitogen-activated protein kinases (MAPK)/Nuclear factor kappa-B (NF-κB) pathway. NBP treatment attenuated renal I/R-induced brain tissue damage and learning and memory dysfunction. NBP treatment inhibited apoptosis and promoted blood-brain barrier restoration and microangiogenesis. Also, it decreased oxidative stress levels and pro-inflammatory factor expression in renal I/R rats. Furthermore, NBP enhanced BMVECs’ viability and tube-forming capacity while inhibiting apoptosis and oxidative stress. Notably, the alleviating effects of NBP were attributed to Nrf2/HO-1 pathway activation and NOD2/MAPK/NF-κB inhibition. This study demonstrates that NBP maintains BBB function by activating the Nrf2/HO-1 pathway and inhibiting the NOD2/MAPK/NF-κB pathway to suppress inflammation and oxidative stress, thereby alleviating renal I/R-induced brain injury.</p

<i>N</i>‑Pyridineium-2-yl Darrow Red Analogue: Unique Near-Infrared Lysosome-Biomarker for the Detection of Cancer Cells

The lysosome-targetable OFF–ON type pH sensor that does not emit at pH = 4.0 is adopted for the selective detection of cancer cells, and the acidity difference of lysosomes in cancer and normal cells is verified. Three pH probes based on Darrow Red derivatives were designed and prepared that were demonstrated to be lysosome-specific biomarkers with inducible emission at 580–850 nm by the comparable in cellular imaging assays using HeLa, KB, and V79 cells. Of these, a pyridineium-2-yl Darrow Red analogue with a p<i>K</i>_a of 2.4 was found to be a lysosome tracker for cancer cells, it is a unique pH sensor for the optical identification and distinction of cancer cells from normal cells and has potential application as a fluorescent biomaker of cancer cells in <i>in vitro</i> assays

Reversible Near-Infrared pH Probes Based on Benzo[<i>a</i>]phenoxazine

Several benzo­[<i>a</i>]­phenoxazine derivatives containing substituted N-aromatic groups are evaluated for their pH-dependent absorption and emission properties. Among the compounds exhibiting optical responses under near-neutral and subacid pH conditions, benzo­[<i>a</i>]­phenoxazine derivatives with an electron-withdrawing aromatic group attached to nitrogen of the imino group show potential application as near-infrared pH sensors. Three water-soluble pH probes based on benzo­[<i>a</i>]­phenoxazine with different pyridinium structures are designed and synthesized. Their reversible pH-dependent emissions in buffer solution containing 0.1% dimethyl sulfoxide (DMSO) locate in 625–850 nm with the fluorescent enhancement of 8.2–40.1 times, and their calculated p<i>K</i>_a values are 2.7, 5.8, and 7.1, respectively. A composite probe containing the three benzo­[<i>a</i>]­phenoxazines shows a linear pH–emission relationship in the range of pH 1.9–8.0. Real-time detection of intracellular pH using an in vitro assay with HeLa cells is also reported