Fenugreek extract improves diabetes-induced endothelial dysfunction via the arginase 1 pathway.

Endothelial dysfunction (ED) is an initiating trigger and key factor in vascular complications, leading to disability and mortality in individuals with diabetes. The research concerning therapeutic interventions for ED has gained considerable interest. Fenugreek, a commonly used edible plant in dietary consumption, has attracted significant attention due to its management of diabetes and its associated complications. The research presented in this study examines the potential therapeutic benefits of fenugreek in treating ED and investigates the underlying mechanism associated with its effects. The analysis on fenugreek was performed using 70% ethanol extract, and its chemical composition was analyzed using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). In total, we identified 49 compounds present in the fenugreek extract. These compounds encompass flavonoids, saponins, and phospholipids. Then, the models of ED in streptozotocin-induced diabetic mice and high glucose-induced isolated rat aortas were established for research. Through vascular function testing, it was observed that fenugreek extract effectively improved ED induced by diabetes or high glucose. By analyzing the protein expression of arginase 1 (Arg1), Arg activity, Arg1 immunohistochemistry, nitric oxide (NO) level, and the protein expression of endothelial nitric oxide synthase (eNOS), p38 mitogen-activated protein kinase (p38 MAPK), and p-p38 MAPK in aortas, this study revealed that the potential mechanism of fenugreek extract in anti-ED involves the downregulation of Arg1, leading to enhanced NO production. Furthermore, analysis of serum exosomes carrying Arg activity indicates that fenugreek may decrease the activity of Arg transported by serum exosomes, potentially preventing the increase in Arg levels triggered by the uptake of serum exosomes by vascular endothelial cells. In general, this investigation offers valuable observations regarding the curative impact of fenugreek extract on anti-ED in diabetes, revealing the involvement of the Arg1 pathway in its mechanism.

Targeted isolation and identification of bioactive pyrrolidine alkaloids from Codonopsis pilosula using characteristic fragmentation-assisted mass spectral networking.

Codonopsis pilosula (CP), a well-known food medicine homology plant, is commonly used in many countries. In our preliminary study, a series of pyrrolidine alkaloids with high MS responses were detected as characteristic absorbed constituents in rat plasma after oral administration of CP extract. However, their structures were unclear due to the presence of various isomers and the lack of reference standards. In the present study, an MS-guided targeted isolation of pyrrolidine alkaloids of CP extract was performed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS). For data analysis under fast data directed acquisition mode (Fast-DDA), an effective approach named characteristic fragmentation-assisted mass spectral networking was successfully applied to discover new pyrrolidine alkaloids with high MS response in CP extract. As a result, seven new pyrrolizidine alkaloids [codonopyrrolidiums C-I (3-9)], together with two known ones (1 and 2), were isolated and identified by NMR spectral analysis. Among them, codonopyrrolidium B (1), codonopyrrolidium D (4) and codonopyrrolidium E (5) were evaluated for lipid-lowering activity, and they could improve high fructose-induced lipid accumulation in HepG2 cells. In addition, the characteristic MS/MS fragmentation patterns of these pyrrolizidine alkaloids were investigated, and 17 pyrrolidine alkaloids were identified. This approach could accelerate novel natural products discovery and characterize a class of natural products with MS/MS fragmentation patterns from similar chemical scaffolds. The research also provides a chemical basis for revealingin vivo effective substances in CP.

Qili Qiangxin, a compound herbal medicine formula, alleviates hypoxia-reoxygenation-induced apoptotic and autophagic cell death via suppression of ROS/AMPK/mTOR pathway in vitro.

OBJECTIVE: Qili Qiangxin (QLQX), a compound herbal medicine formula, is used effectively to treat congestive heart failure in China. However, the molecular mechanisms of the cardioprotective effect are still unclear. This study explores the cardioprotective effect and mechanism of QLQX using the hypoxia-reoxygenation (H/R)-induced myocardial injury model. METHODS: The main chemical constituents of QLQX were analyzed using high-performance liquid chromatography-evaporative light-scattering detection. The model of H/R-induced myocardial injury in H9c2 cells was developed to simulate myocardial ischemia-reperfusion injury. Apoptosis, autophagy, and generation of reactive oxygen species (ROS) were measured to assess the protective effect of QLQX. Proteins related to autophagy, apoptosis and signalling pathways were detected using Western blotting. RESULTS: Apoptosis, autophagy and the excessive production of ROS induced by H/R were significantly reduced after treating the H9c2 cells with QLQX. QLQX treatment at concentrations of 50 and 250 µg/mL caused significant reduction in the levels of LC3II and p62 degradation (P < 0.05), and also suppressed the AMPK/mTOR signalling pathway. Furthermore, the AMPK inhibitor Compound C (at 0.5 µmol/L), and QLQX (250 µg/mL) significantly inhibited H/R-induced autophagy and apoptosis (P < 0.01), while AICAR (an AMPK activator, at 0.5 mmol/L) increased cardiomyocyte apoptosis and autophagy and abolished the anti-apoptotic effect of QLQX. Similar phenomena were also observed on the expressions of apoptotic and autophagic proteins, demonstrating that QLQX reduced the apoptosis and autophagy in the H/R-induced injury model via inhibiting the AMPK/mTOR pathway. Moreover, ROS scavenger, N-Acetyl-L-cysteine (NAC, at 2.5 mmol/L), significantly reduced H/R-triggered cell apoptosis and autophagy (P < 0.01). Meanwhile, NAC treatment down-regulated the ratio of phosphorylation of AMPK/AMPK (P < 0.01), which showed a similar effect to QLQX. CONCLUSION: QLQX plays a cardioprotective role by alleviating apoptotic and autophagic cell death through inhibition of the ROS/AMPK/mTOR signalling pathway.

Periplocymarin alleviates pathological cardiac hypertrophy via inhibiting the JAK2/STAT3 signalling pathway.

Pathological cardiac hypertrophy is the most important risk factor for developing chronic heart failure. Therefore, the discovery of novel agents for treating pathological cardiac hypertrophy remains urgent. In the present study, we examined the therapeutic effect and mechanism of periplocymarin (PM)-mediated protection against pathological cardiac hypertrophy using angiotensinII (AngII)-stimulated cardiac hypertrophy in H9c2 cells and transverse aortic constriction (TAC)-induced cardiac hypertrophy in mice. In vitro, PM treatment significantly reduced the surface area of H9c2 cells and expressions of hypertrophy-related proteins. Meanwhile, PM markedly down-regulated AngII-induced translocation of p-STAT3 into the nuclei and enhanced the phosphorylation levels of JAK2 and STAT3 proteins. The STAT3 specific inhibitor S3I-201 or siRNA-mediated depleted expression could alleviate AngII-induced cardiac hypertrophy in H9c2 cells following PM treatment; however, PM failed to reduce the expressions of hypertrophy-related proteins and phosphorylated STAT3 in STAT3-overexpressing cells, indicating that PM protected against AngII-induced cardiac hypertrophy by modulating STAT3 signalling. In vivo, PM reversed TAC-induced cardiac hypertrophy, as determined by down-regulating ratios of heart weight to body weight (HW/BW), heart weight to tibial length (HW/TL) and expressions of hypertrophy-related proteins accompanied by the inhibition of the JAK2/STAT3 pathway. These results revealed that PM could effectively protect the cardiac structure and function in experimental models of pathological cardiac hypertrophy by inhibiting the JAK2/STAT3 signalling pathway. PM is expected to be a potential lead compound of the novel agents for treating pathological cardiac hypertrophy.

Design and prediction of PIT devices through deep learning.

Graphene material has excellent performance and unique variable carrier density characteristics, making it an excellent mid-infrared material. And deep learning makes it possible to quickly design mid-infrared band devices with good performance. A graphene nano-ring-symmetric sector-shaped disk array structure based on the PIT principle is proposed here for sensing. The influence of structural parameters and Fermi energy changes are studied. And its FOM (Figure Of Merit) can reach 28.7; the sensitivity is 574 cm-1 / RIU (Refractive Index Unit). At the same time, we designed a six-layer deep learning network that can predict structural parameters and curve predictions. When predicting structural parameters, its MAPE (Mean Absolute Percentage Error) converges to 0.5. In curve prediction, MSE (Mean Square Error) converges to 1.2. It shows that predictions can be made very well. This paper proposes a symmetrical sector disk array structure and a 6-layer deep learning network. And the deep neural network designed based on the device data has good prediction accuracy under the premise of ensuring the network is simple. This will lay a good foundation for future sensor design and device acceleration optimization design.

Effect of high temperature stress on heat shock protein expression and antioxidant enzyme activity of two morphs of the mud crab Scylla paramamosain.

The present study aimed to investigate the effect rapid temperature change from moderate temperature to high temperatures on heat shock protein (HSP) expression and antioxidant enzyme activities in mud crabs. Two mud crabs, one with one spine on the outer margin of the carpus of cheliped (Sp1) and another with two spines (Sp2), were acclimated at 25 °C and then transferred to a 33 °C environment, and HSP expression and antioxidant enzyme activity were assessed. HSP70 and HSP60 were markedly up-regulated in the gills and hepatopancreas of Sp1 and Sp2 after exposure to 35 °C. Exposure to 35 °C also significantly increased superoxide dismutase and catalase activity in the gills of Sp1 and Sp2, with transient changes in hepatopancreas. Apart from changes in antioxidant enzyme activities, HSPs were highly up-regulated after exposure to 37 °C, especially for HSP70. Gill HSP70 expression in Sp2 was 6.1 folds that of the control after 24 h of exposure to 37 °C, and 9.2 folds that of Sp1. Moreover, exposure to 37 °C further up-regulated HSP70 in the hepatopancreas of Sp1, compared to that in Sp2. Hence, HSPs play important roles in thermotolerance in S. paramamosain and Sp1 might have a stronger tolerance to hyperthermal stress than Sp2.