Mechanisms predictive of Tibetan Medicine Sophora moorcroftiana alkaloids for treatment of lung cancer based on the network pharmacology and molecular docking.

BACKGROUND: Leguminous Sophora moorcroftiana (SM) is a genuine medicinal material in Tibet. Many research results have reveal the Sophora moorcroftiana alkaloids (SMA), as the main active substance, have a wide range of effects, such as antibacterial, antitumor and antiparasitic effects. However, there are few reports on the inhibition of lung cancer (LC) and its inhibitory mechanism, and the pharmacological mechanism of SMA is still unclear, Therefore, exploring its mechanism of action is of great significance. METHODS: The SMA active components were obtained from the literature database. Whereas the corresponding targets were screened from the PubChem and PharmMapper database, UniProt database were conducted the correction and transformation of UniProt ID on the obtained targets. The GeneCards and OMIM databases identified targets associated with LC. Venny tools obtained the intersection targets of SMA and LC. R language and Cytoscape software constructed the visual of SMA - intersection targets - LC disease network. The intersection targets protein-protein interaction (PPI) network were built by the STRING database. The functions and pathways of the common targets of SMA and LC were enriched by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking And A549 cells vitro experiment were performed to further validate our finding. RESULTS: We obtained six kinds of alkaloids in SM, 635 potential targets for these compounds, and 1,303 genes related to LC. SMA and LC intersection targets was 33, including ALB, CCND1, ESR1, NOTCH1 and AR. GO enrichment indicated that biological process of SMA was mainly involved in the positive regulation of transcription and nitric oxide biosynthetic process, and DNA-templated, etc. Biological functions were mainly involved in transcription factor binding and enzyme binding, etc. Cell components were mainly involved in protein complexes, extracellular exosome, cytoplasm and nuclear chromatin, etc., Which may be associated with its anti-LC effects. KEGG enrichment analysis showed that main pathways involved in the anti-LC effects of SMA, including pathway in cancer, non small-cell lung cancer, p53, PI3K-Akt and FOXO signaling pathways. Molecular docking analyses revealed that the six active compounds had a good binding activity with the main therapeutic targets 2W96, 2CCH and 1O96. Experiments in vitro proved that SMA inhibited the proliferation of LC A549 cells. CONCLUSIONS: Results of the present study, we have successfully revealed the SMA compounds had a multi-target and multi-channel regulatory mechanism in treatment LC, These findings provided a solid theoretical reference of SMA in the clinical treatment of LC.

Lactobacillus reuteri derived from horse alleviates Escherichia coli-induced diarrhea by modulating gut microbiota.

Diarrhea is a prevalent health issue in farm animals and poses a significant challenge to the progress of animal husbandry. Recent evidence suggested that probiotics can alleviate diarrhea by maintaining gut microbial balance and enhancing the integrity of the intestinal barrier. However, there is a scarcity of studies investigating the efficacy of equine Lactobacillus reuteri in relieving E. coli-induced diarrhea. Hence, this study aimed to examine the potential of equine-derived Lactobacillus reuteri in alleviating E. coli diarrhea from the perspective of gut microbiota. Results demonstrated that supplementation of Lactobacillus reuteri had the potential to alleviate diarrhea induced by E. coli infection and restore the decline of tight junction genes, such as Claudin-1 and ZO-1. Additionally, Lactobacillus reuteri supplementation can restore the expression of inflammatory factors (IL-6, IL-10, TNF-α, and IFN-γ) and reduce colon inflammatory damage. Diversity analysis, based on amplicon sequencing, revealed a significant reduction in the diversity of gut microbiota during E. coli-induced diarrhea. Moreover, there were notable statistical differences in the composition and structure of gut microbiota among the different treatment groups. E. coli could induce gut microbial dysbiosis by decreasing the abundance of beneficial bacteria, including Lactobacillus, Bifidobacterium, Ligilactobacillus, Enterorhabdus, and Lachnospiraceae_UCG_001, in comparison to the control group. Conversely, supplementation with Lactobacillus reuteri could restore the abundance of beneficial bacteria and increase the diversity of the gut microbiota, thereby reshaping gut microbiota. Additionally, we also observed that supplementation with Lactobacillus reuteri alone improved the gut microbial composition and structure. In summary, the findings suggest that Lactobacillus reuteri can alleviate E. coli-induced diarrhea by preserving the integrity of the intestinal barrier and modulating the composition of the gut microbiota. These results not only contribute to understanding of the mechanism underlying the beneficial effects of Lactobacillus reuteri in relieving diarrhea, but also provide valuable insights for the development of probiotic products aimed at alleviating diarrheal diseases.

Structural characteristic of polysaccharide isolated from Nostoc commune, and their potential as radical scavenging and antidiabetic activities.

In this paper, Nostoc commune crude polysaccharide was extracted by heating and Ultrasonic-assisted methods separately, homogeneous polysaccharide HNCP3 and UNCP4 were obtained after purified by DEAE-52 cellulose column chromatography and Sephacryl G-100 gel column chromatography. The structures of HNCP3 and UNCP4 were characterized by molecular weight determination, infrared spectroscopy, DSC detection, sodium periodate oxidation, smith degradation reaction and methylation analysis. The conformation of the solution was studied by SEM and AFM. The results showed that the Ultrasonic-assisted extraction had effects on the molecular weight, monosaccharide composition, molar ratio and configuration of Nostoc commune. The main chain of HNCP3 and UNCP4 was → 6)-D-Glcp(1→ and → 2, 6)-D-Glcp, but UNCP4 contained 1, 2, 6-galactose and 2, 3-Me2-D-Ara branches, while HNCP3 did not. The results of the monosaccharides composition of indicated that mannose was presented in both HNCP3 and UNCP4. SEM and AFM showed that the structure of UNCP4 was helical, and the solution conformations of HNCP3 and UNCP4 were different in different solution environments. Studies on DPPH radicals, superoxide anions, and hydroxyl radicals scavenging abilities showed that UNCP4 had higher antioxidant activity, while studies on the antidiabetic activities showed that the hypoglycemic effect of UNCP4 was stronger than that of HNCP3. Therefore, Ultrasonic-assisted extraction (UAE) increases the bioactivity of Nostoc commune polysaccharide (NCP) as well as the extraction rate.

Molecularly imprinted polymer-specific solid-phase extraction for the determination of 4-hydroxy-2(3H)benzoxazolone isolated from Acanthus ilicifolius Linnaeus using high-performance liquid chromatography-tandem mass spectrometry.

The minor constituent found in Acanthus ilicifolius Linnaeus, 4-hydroxy-2 (3H) benzoxazolone alkaloid (HBOA), has a range of versatile applications. Herein, a quick and straightforward method for extracting HBOA from A. ilicifolius Linnaeus was proposed. HBOA was used as a template, whereas methacrylic acid, ethylene glycol dimethacrylate, and acetonitrile were used as functional monomers, cross-linkers, and porogens, respectively. Molecularly imprinted polymers (MIPs) were synthesized by precipitation polymerization, and their adsorption isotherms, dynamics, and selective binding ability were characterized and analyzed. The results showed that the adsorption amount of the template was 90.18 mg/g. The MIPs were used as solid-phase extraction fillers and actual sample extraction columns, with a linear range of 0-100 µg/L, average recovery of 78.50-101.12%, and a relative standard deviation of 1.20-3.26%. The HBOA concentrations in the roots, stems, and leaves were 1,226, 557, and 205 µg/g, respectively. In addition, MIP-SPE was successfully used in isolating and purifying HBOA from different parts of A. ilicifolius Linnaeus, indicating its effectiveness in extracting and determining HBOA in other herbs.

Preparation of complex microcapsules of soluble polysaccharide from Glycyrrhiza uralensis and its application in wound repair and scar inhibition.

The extraction process of Glycyrrhiza soluble polysaccharide (GP) was optimized by RSM, a rat trauma model was established via longitudinal incision on the back skin. The effects of GP combined with microcapsule collagen on the repair of rat injury model were discussed at different levels, Based on the content of hydroxyproline at the whole animal level, the proliferation of granulation tissue stained by HE, the number of microvessels labeled by CD34, the production of collagen fibers stained by Masson, the level of phosphorylation of STAT3 protein and that of VEGF at protein level were investigated. The results showed that after the administration of GP combined with microcapsules, the content of hydroxyproline in granulation tissue increased, the proliferation of capillaries and fibroblasts in granulation tissue became active, and the number of microvessels in wound increased. The formation density of collagen fibers was uniform and orderly. GP combined with microcapsules could activate the expression of p-STAT3 and VEGF proteins and up-regulate the transcription level of VEGF mRNA and miRNA-21 genes. Furthermore, GP combined with microcapsules could accelerate wound healing and promote neovascularization.