Role and mechanism of esketamine in improving postoperative cognitive dysfunction in aged mice through the TLR4/MyD88/p38 MAPK pathway.

Postoperative cognitive dysfunction (POCD) is a significant concern for the elderly population worldwide. This study explored the effects of esketamine on aged mice with POCD and investigate its mechanism of action involving the TLR4/MyD88/MAPK pathway. We administrated esketamine, along with lipopolysaccharide or anisomycin, to the aged POCD mouse models. We assessed their cognitive function using the Morris water maze test. Additionally, we evaluated histopathological changes/neuronal apoptosis in the mouse hippocampal CA1 area through HE/TUNEL stainings. Furthermore, we measured IL-1ß/IL-6/TNF-α/TLR4/MyD88/MAPK (p-p38/p38) levels in mouse hippocampal tissues using ELISA/RT-qPCR/Western blotting. Lastly, we analyzed the interaction between TLR4 and MyD88 using a co-immunoprecipitation assay. Our findings showed that esketamine effectively mitigated POCD in aged mice. This was evident from the improved cognitive performance observed in the Morris water maze test, characterized by reduced escape latency/increased number of platform crossing/a higher percentage of time spent in the target quadrant. Furthermore, esketamine exhibited a protective effect against neuronal apoptosis and reduced the levels of inflammatory factors. These findings suggest that esketamine exerts an anti-inflammatory effect by downregulating TLR4/MyD88, thereby attenuating the inflammatory response associated with POCD. Additionally, esketamine suppressed the p38 MAPK pathway by inhibiting the TLR4/MyD88 signaling cascade. Esketamine demonstrated its efficacy in improving postoperative inflammation and cognitive impairment in aged mice by inhibiting the TLR4/MyD88 pathway. The activation of p38 MAPK signaling diminished the beneficial effects of esketamine in aged POCD mice. Collectively, the underlying mechanism of esketamine in mitigating POCD in aged mice involves the suppression of the TLR4/MyD88/p38 MAPK pathway.

Research on antioxidant performance of diglucosyl gallic acid and its application in emulsion cosmetics.

OBJECTIVE: Diglucosyl gallic acid is a whitening active with powerful whitening function. When it acts on human skin, microorganisms on the skin surface and part of the stratum corneum produce α-glucosidase to sever the glucose bond of diglucosyl gallic acid, thereby converting part of diglucosyl gallic acid into gallic acid, acting on the skin and exerting the excellent effects of diglucosyl gallic acid and gallic acid at the same time. Diglucosyl gallic acid has high stability and water solubility, it can reduce free radical generation, inhibit tyrosinase generation, prevent melanin transfer, and control skin inflammation. The present study investigates the in vitro tyrosinase inhibition activity, antioxidant capacity of diglucosyl gallic acid as well as its clinical efficacy as a cosmetic ingredient. METHODS: Taking VC and gallic acid as controls, the pH = 6.8, 0.05 mmol/L Na2HPO4-NaH2PO4 buffer solution was prepared to test the tyrosinase inhibitory activity and antioxidant capacity of diglucosyl gallic acid respectively. Using arbutin and nicotinamide, two common cosmetic raw materials as controls, 20 volunteers (aged 20-35 years old) were selected for the test. (2 ± 0.1) mg/cm2 take the lotion to be tested and apply it to the test part evenly, twice a day, volunteers are not allowed to use sunscreen or other sunscreen products during the study period. RESULTS: The results show that diglucosyl gallic acid has a stronger ability to inhibit the activity of tyrosinase compared with VC, and its IC50 value is 2.68 mg/ mL. Their potential antioxidant activities are further evaluated by the DPPH (α, α-diphenyl-ß-picrylhydrazyl) method and the ABTS [2,2´-azinobis-(3-ethylbenz othiazoline-6-sulphonate)] radical cation (ABTS+) method, in which the gallic acid demonstrates a better performance than the traditional antioxidant vitamin C (VC), while the diglucosyl gallic acid shows poorer performance. As to the reducing ability, VC has the best performance, much better than gallic acid and diglucosyl gallic acid. Furthermore, through clinical experiments, it is shown the application of the diglucosyl gallic acid as a cosmetic ingredient can considerably improve the brightness of the skin and meanwhile reduce the area of ultraviolet spots, melanin and erythema over time. CONCLUSION: The above in vitro and in vivo studies on diglucosyl gallic provide the basis for its future application development in cosmetics.

OBJECTIF: L'acide diglucosyl gallique est un actif blanchissant doté d'une puissante fonction blanchissante. Lorsqu'il agit sur la peau humaine, les microorganismes à la surface de la peau et une partie de la couche cornée produisent de l'α-glucosidase pour rompre la liaison glucose de l'acide diglucosyl gallique, convertissant ainsi une partie de l'acide diglucosyl gallique en acide gallique, agissant sur la peau et exerçant les excellents effets de l'acide diglucosyl gallique et de l'acide gallique en même temps. L'acide diglucosyl gallique a une stabilité et une solubilité dans l'eau élevées, il peut réduire la génération de radicaux libres, inhiber la génération de tyrosinase, empêcher le transfert de mélanine et contrôler l'inflammation cutanée. La présente étude examine l'activité d'inhibition de la tyrosinase in vitro, la capacité antioxydante de l'acide diglucosyl gallique ainsi que son efficacité clinique en tant qu'ingrédient cosmétique. MÉTHODE: En prenant VC (vitamine C) et l'acide gallique comme témoins, la solution tampon pH = 6,8, 0,05 mmol / L Na2HPO4-NaH2PO4 a été préparée pour tester respectivement l'activité inhibitrice de la tyrosinase et la capacité antioxydante de l'acide diglucosyl gallique. En utilisant l'arbutine et le nicotinamide, deux matières premières cosmétiques courantes comme témoins, 20 volontaires (âgés de 20 à 35 ans) ont été sélectionnés pour le test. Prendre la lotion à tester et l'appliquer (2 ± 0,1) mg/cm2 uniformément sur la partie testée, deux fois par jour, les volontaires ne sont pas autorisés à utiliser de crème solaire ou d'autres produits de protection solaire pendant la période d'étude. RÉSULTATS: Les résultats montrent que l'acide diglucosyl gallique a une capacité plus forte à inhiber l'activité de la tyrosinase par rapport au VC, et sa valeur IC50 est de 2,68 mg/mL. Leurs activités antioxydantes potentielles sont ensuite évaluées par la méthode DPPH (α, α-diphényl-ß-picrylhydrazyl) et la méthode ABTS [2,2´-azinobis-(3-ethylbenzothiazoline-6-sulfonate)] radical cation (ABTS+), dans laquelle l'acide gallique présente de meilleures performances que la vitamine C (VC) antioxydante traditionnelle, tandis que l'acide diglucosyl gallique présente de moins bonnes performances. Quant au pouvoir réducteur, la VC a les meilleures performances, bien meilleures que l'acide gallique et l'acide diglucosyl gallique. De plus, à travers des expériences cliniques, il est démontré que l'application de l'acide diglucosyl gallique en tant qu'ingrédient cosmétique peut considérablement améliorer la luminosité de la peau et réduire en même temps la surface des taches de soleil, de la mélanine et de l'érythème au fil du temps. CONCLUSION: Les études in vitro et in vivo ci-dessus sur le diglucosyl gallique constituent la base de son futur développement d'applications en cosmétique.