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Pueraria lobata (Willd.) Ohwi is a traditional medicinal herb that has been extensively used in Chinese medicine for various therapeutic purposes. In this study, twelve chemical constituents were isolated from the roots of P. lobata, comprising three puerosides (compounds 1–3), six alkaloids (compounds 4–9), and three additional compounds (compounds 10–12). Notably, compound 1 (4R-pueroside B) was identified as a novel compound. The structures of all compounds were elucidated using a range of spectroscopic techniques, including CD spectroscopy for the first-time determination of the absolute configurations of pueroside B isomers (compounds 1 and 2). Enzyme inhibition assays revealed that, with the exception of compound 2, all isolated compounds exhibited varying degrees of α-glucosidase and α-amylase inhibitory activity. Remarkably, compound 12 demonstrated IC50 values of 23.25 μM for α-glucosidase inhibition and 27.05 μM for α-amylase inhibition, which are superior to those of the positive control, acarbose (27.05 μM and 36.68 μM, respectively). Additionally, compound 11 exhibited inhibitory activity against α-glucosidase and α-amylase comparable to the positive control, acarbose. Molecular docking studies indicated that compound 12 interacts with the active sites of the enzymes via hydrogen bonds, van der Waals forces, and hydrophobic interactions, which likely contribute to their inhibitory effects. These findings suggest that the chemical constituents of P. lobata could be potential natural sources of α-amylase and α-glucosidase inhibitors, with compound 12 being particularly promising for further investigation. [ABSTRACT FROM AUTHOR]

Litsea cubeba, which is found widely distributed across the Asian region, functions as both an economic tree and a medicinal plant with a rich historical background. Previous investigations into its chemical composition and biological activity have predominantly centered on volatile components, leaving the study of non-volatile components relatively unexplored. In this study, we employed UPLC-HRMS technology to analyze the non-volatile components of L. cubeba branches and leaves, which successfully resulted in identifying 72 constituents. Comparative analysis between branches and leaves unveiled alkaloids, organic acids, and flavonoids as the major components. However, noteworthy differences in the distribution of these components between branches and leaves were observed, with only eight shared constituents, indicating substantial chemical variations in different parts of L. cubeba. Particularly, 24 compounds were identified for the first time from this plant. The assessment of antioxidant activity using four methods (ABTS, DPPH, FRAP, and CUPRAC) demonstrated remarkable antioxidant capabilities in both branches and leaves, with slightly higher efficacy observed in branches. This suggests that L. cubeba may act as a potential natural antioxidant with applications in health and therapeutic interventions. In conclusion, the chemical composition and antioxidant activity of L. cubeba provides a scientific foundation for its development and utilization in medicine and health products, offering promising avenues for the rational exploitation of L. cubeba resources in the future. [ABSTRACT FROM AUTHOR]

Sinisan (SNS) has been used to treat psychosomatic diseases of the digestive system. But little is known about how SNS affects water immersion restraint stress (WIRS). To study the effects of SNS on colonic tissue injury in the WIRS model. Forty-eight Kunming (KM) mice were randomized into 6 groups (n = 8): The control and WIRS groups receiving deionized water; the SNS low-dose (SL, 3.12 g/kg/d), SNS middle-dose (SM, 6.24 g/kg/d), SNS high-dose (SH, 12.48 g/kg/d), and diazepam (DZ, 5 mg/kg/d) groups; each with two daily administrations for 5 consecutive days. The 5 treatment groups were subjected to WIRS for 24 h on day 6. The effects of SNS on colon tissue injury caused by WIRS were assessed by changes in colon histology, inflammatory cytokines, brain-gut peptides, and tight junction (TJ) proteins levels. 16S rRNA gene sequencing was used to detect the regulation of the gut microbiota. SNS pretreatment significantly reduced TNF-α (0.75- to 0.81-fold), IL-6 (0.77-fold), and IFN-γ (0.69-fold) levels; and increased TJ proteins levels, such as ZO-1 (4.06- to 5.27-fold), claudin-1 (3.33- to 5.14-fold), and occludin (6.46- to 11.82-fold). However, there was no significant difference between the levels of substance P (SP) and vasoactive intestinal peptide (VIP) in the control and WIRS groups. SNS regulated the composition of gut microbiota in WIRS mice. The positive effects of SNS on WIRS could provide a theoretical basis to treat stress-related gastrointestinal disorders. [ABSTRACT FROM AUTHOR]

Therapeutic drugs of chronic neuralgia have a high risk of addiction, making it crucial to identify novel drugs for chronic neuralgia. This study aimed to explore the therapeutic effect of paeoniflorin on chronic sciatica via inhibiting Schwann cell apoptosis. 28 SD rats were randomly divided into four groups, including the sham operation group, chronic constriction injury (CCI) group, mecobalamin group, and paeoniflorin group. The therapeutic effect and mechanism of paeoniflorin were evaluated via rat and cell experiments. Mechanical, hot, or cold hyperalgesia was induced in the rats after CCI operation, while paeoniflorin relieved chronic neuralgia. Besides, paeoniflorin decreased the levels of IL1, IL6, TNF‐α, CRP, and LPS and increased the level of IL10 in serum. As for the sciatic nerve, the number of inflammatory cells was decreased, and Schwann cells were present after paeoniflorin treatment, and paeoniflorin promoted the recovery of nerve structure. In cell experiments, LPS induced Schwann cell apoptosis via the TLR4/NF‐kB pathway. And paeoniflorin attenuated LPS‐induced Schwann cell apoptosis by decreasing the levels of TLR4, p‐NF‐kB, caspase3, cleaved‐caspase3, and cleaved‐caspase7. Overall, these results suggest that paeoniflorin alleviates chronic sciatica by decreasing inflammatory factor levels and promotes the repair of damaged nerves by reducing Schwann cell apoptosis. [ABSTRACT FROM AUTHOR]

Switching microglial polarization from the M1 to M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). Toll‐like receptor 4 (TLR4) is activated by lipopolysaccharide (LPS). Uncontrolled activation of TLR4 has been proven to trigger chronic inflammation. Kaempferol, a dietary flavonoid, is known to have anti‐inflammatory properties. This study is aimed to investigate the analgesic and anti‐inflammatory effects and the underlying mechanisms of kaempferol, which were explored with an NP model in vivo and LPS‐induced injury in microglial BV2 cells in vitro. The levels of proinflammatory cytokines were evaluated. H&E staining and immunohistochemistry were used to assess the sciatic nerve condition after chronic constriction injury surgery. Western blotting and immunofluorescence were used to determine whether TLR4/NF‐ĸB signaling pathway plays a major role in kaempferol‐mediated alleviation of neuroinflammation. Quantitative real‐time polymerase chain reaction and flow cytometry were used to examine the modulator effect of kaempferol on microglial M1/M2 polarization. We found that kaempferol treatment can significantly reduce NP and proinflammatory cytokine production. Kaempferol attenuated the activation of TLR4/NF‐κB pathways in LPS‐activated BV2 cells. The analgesic effects of kaempferol on NP may be due to inhibition of microglia activation and switching the M1 to M2 phenotype. [ABSTRACT FROM AUTHOR]

Late-stage carotid atherosclerosis has a high incidence rate and may lead to various cerebrovascular diseases. The gene expression profile GSE100927 was selected to identify differentially expressed genes (DEGs) in carotid atherosclerosis. Subsequently, protein-protein interaction, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted. Furthermore, experimental verification was performed using human umbilical vein endothelial cells (HUVECs), human aortic vascular smooth muscle cells (HAVSMCs) and Tohoku Hospital Pediatrics-1 (THP-1)-induced macrophages. The groups were as follows: Control group, solvent control group and palmitic acid group. The levels of reactive oxygen species (ROS) in the three cell types were detected by flow cytometry or fluorescence microscopy. Furthermore, apoptosis of HUVECs and HAVSMCs was assessed by flow cytometry and the nuclear Hoechst 33258 staining of THP-1-induced macrophages was performed. Male late-stage carotid atherosclerosis samples, including 10 control samples and 21 atherosclerosis samples, were selected. Pathway enrichment analysis demonstrated that 'Toll-like receptor signaling pathway' was the top pathway associated with the DEGs. MMP7, MMP9, IL1β, C-C motif chemokine ligand 4 (CCL4), secreted phosphoprotein 1 (SPP1), CCL3 and interferon regulatory factor 5 (IRF5) were selected for experimental verification. Palmitic acid increased the ROS levels and the apoptosis rates of HUVECs and HAVSMCs. However, it did not increase the levels of ROS and did not shrink the nuclei of THP-1-induced macrophages. Furthermore, palmitic acid increased the mRNA levels of IL1β, CCL4, SPP1, CCL3, IRF5, MMP7 and MMP9 in HUVECs and THP-1-induced macrophages, and increased the mRNA levels of CCL4 and MMP9 in HAVSMCs. In conclusion, IL1β, CCL3, CCL4, SPP1, IRF5, MMP7 and MMP9 are important markers of late-stage carotid atherosclerosis. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess the protective effects of 18β-GA against hydrogen peroxide (H2O2)-induced injury. First, the SMILES annotation for 18β-GA was used to search PubChem and for reverse molecular docking in Swiss Target Prediction, the Similarity Ensemble Approach Search Server and the TargetNet database to obtain potential targets. Injury-related molecules were obtained from the GeneCards database and the predicted targets of 18β-GA for injury treatment were selected by Wayne diagram analysis. Subsequently, Kyoto Encyclopedia of Genes and Genomes analysis was performed by WebGestalt. The experimental cells were assorted into control, model, 10 µM SB203580-treated, 5 µM 18β-GA-treated and 10 µM 18β-GA-treated groups. Hoechst 33258 staining was performed and intracellular reactive oxygen species (ROS) levels, cell apoptosis, Bcl-xl, Bcl-2, Bad, Bax, cleaved-caspase 3, cleaved-caspase 7, transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) levels, as well as p38 MAPK phosphorylation were measured. The 'Inflammatory mediator regulation of TRP channels' pathway was selected for experimental verification. The results indicated that 10 µM 18β-GA significantly increased cell viability as compared with the H2O2-treated model group. As suggested by the difference in intracellular ROS fluorescence intensity, 18β-GA inhibited H2O2-induced ROS production in Schwann cells. Hoechst 33258 staining indicated that 18β-GA reversed chromatin condensation and the increase in apoptotic nuclei following H2O2 treatment. Furthermore, flow cytometry suggested that 18β-GA substantially inhibited H2O2-induced apoptosis. Pre-treatment with 18β-GA obviously reduced Bad, Bax, cleaved-caspase3, cleaved-caspase 7, TRPA1 and TRPV1 levels and p38 MAPK phosphorylation after H2O2 treatment and increased Bcl-2 and Bcl-xl levels. In conclusion, 18β-GA inhibited Schwann cell injury and apoptosis induced by H2O2 and may be a potential drug to prevent peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Abstract: Porous Fe3O4-decorated graphene (GN–Fe3O4) composites with different microstructures were successfully synthesized by a modified two-step method. The microstructure and morphology were confirmed by X-ray diffraction (XRD), transmission electron microscopy and scanning electron microscopy. XRD studies show that the products consist of highly crystallized Fe3O4 but disorderedly stacked GN sheets. Electron microscopy images reveal that Fe3O4 nanoparticles with different sizes and microstructures are uniformly coated on both sides of GN sheets, without large vacancies or apparent aggregation. Electromagnetic wave absorption properties of epoxy containing 30 wt.% GN–Fe3O4 composites were investigated at room temperature in the frequency range of 0.5–18GHz. In particular, the porous, flower-like Fe3O4-decorated GN sample exhibits an enhanced dielectric loss due to the porous microstructure of Fe3O4. The multiple absorbing mechanisms attribute to the improved impedance matching which indicates the as-prepared porous GN–Fe3O4 composites could be a potential candidate for lightweight electromagnetic wave absorption materials. [Copyright &y& Elsevier]