RESUMEN
Peptide glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective drugs for treating type 2 diabetes (T2DM) and have been proven to benefit the heart and kidney. Apart from oral semaglutide, which does not require injection, other peptide GLP-1RAs need to be subcutaneously administered. However, oral semaglutide also faces significant challenges, such as low bioavailability and frequent gastrointestinal discomfort. Thus, it is imperative that advanced oral strategies for peptide GLP-1RAs need to be explored. This review mainly compares the current advantages and disadvantages of various oral delivery strategies for peptide GLP-1RAs in the developmental stage and discusses the latest research progress of peptide GLP-1RAs, providing a useful guide for the development of new oral peptide GLP-1RA drugs.
RESUMEN
Ultrasonic-assisted extraction is a rapid and effective extraction method that uses ultrasound energy and solvents to extract target compounds from various plant matrices. In this study, the ultrasonic-assisted extraction conditions of sour jujube were optimized. A five-level central composite design (CCD) with four variables was used to evaluate ultrasonic treatment variables influencing the total saponin content (TSC), total flavonoid content (TFC), and total phenolic content (TPC) extracted from sour jujube. The solvent concentration, extraction time, ultrasonic power, and solid-to-liquid (S/L) ratio were optimized using aqueous ethanol and methanol solutions as extraction solvents. A central composite design (CCD) was used for an in-depth study, and then the optimal value that could produce the maximum TPC, TFC, TSC, and four in vitro antioxidant activities (scavenging activity of hydroxyl free radicals, ferric-reducing antioxidant power (FRAP), phosphomolybdic acid reduction method, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity) was determined. Hydrogen peroxide-induced oxidative stress experiment confirmed that the Jujube extract could have an antioxidant role in vivo. The relationship between the contents of three compounds and the antioxidant activity in vitro and in vivo was further studied. The results showed that optimizing methanol and ethanol extraction process parameters could improve target components' extraction efficiency. Under the optimum conditions, the TFC and TPC yields of sour jujube by ethanol are better than methanol, while the yield of TSC by methanol is better than ethanol. In vivo data showed that Jujube extract protects against the adverse effects of oxidative stress and improves the life span of female and male Drosophila. This study provides a valuable reference for the full use of Ziziphus jujube, as well as a new direction in food development.
RESUMEN
The fear conditioning-based models of anxiety disorders have been widely used for assessing anxiolytic action. The triple test is an evaluation method for anxiety-like behaviors that integrates the open field, elevated plus maze, and light/dark box, which can comprehensively reflect the anxiety-like behaviors state of animals. However, there are many factors that can affect the evaluation results of anxiety-like behaviors, especially the time of day (morning or afternoon), which are often ignored by most experimental studies. Accordingly, in the present study, we first measured the anxiety-like behavior in the fear conditioning-based model rats by using the triple test in the morning and afternoon, respectively (experiment 1). In experiment 2, the anxiety-like behaviors were evaluated on the 1st, 7th, 10th and 14th day after experiencing foot shock for 4 consecutive days, respectively. The fear-conditioned rats exhibited increased anxiety-like behaviors only in the afternoon and prolonged freezing times either in the morning and afternoon. Furthermore, model rats exhibit increased anxiety-like behaviors in open field, elevated plus maze, and light/dark box on the 1st day; in open field and light/dark box on the 7th day; in elevated plus maze on the 10th day; and in light/dark box on the 14th day after the final foot shock. The results suggested that the time of day had a significant effect on anxiety-like behaviors caused by conditioned fear, and increased in the afternoon vs morning. Moreover, the lasting increased in anxiety-like behavior for 14 days was appropriated to explore the effects of long-term administration of anxiolytics.