[Mechanism of Guizhi Gancao Decoction against myocardial ischemia-reperfusion injury based on network pharmacology and experimental verification].

This study employed network pharmacology to investigate the effect of Guizhi Gancao Decoction(GGD) on myocardial ischemia-reperfusion injury(MI/RI) in rats and decipher the underlying mechanism. Firstly, the chemical components and targets of GGD against MI/RI were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), SwissTargetPrediction, and available articles. STRING and Cytoscape 3.7.2 were used to establish the protein-protein interaction(PPI) network for the common targets, and then Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out for the core targets. The "drug-active component-target-pathway" network was built. Furthermore, molecular docking between key active components and targets was conducted in AutoDock Vina. Finally, the rat model of MI/RI was established, and the myocardial infarction area was measured. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were employed to detect cardiomyocyte pathology and ultrastructural changes. Western blot was employed to determine the expression of related proteins in the myocardial tissue. A total of 75 chemical components of GGD were screened out, corresponding to 318 targets. The PPI network revealed 46 core targets such as tumor protein p53(TP53), serine/threonine kinase 1(AKT1), signal transducer and activator of transcription 3(STAT3), non-receptor tyrosine kinase(SRC), mitogen-activated protein kinase 1(MAPK1), MAPK3, and tumor necrosis factor(TNF). According to GO and KEGG enrichment analyses, the core targets mainly affected the cell proliferation and migration, signal transduction, apoptosis, and transcription, involving advanced glycation end products-receptor(AGE-RAGE), MAPK and other signaling pathways in cancers and diabetes complications. The molecular docking results showed that the core components of GGD, such as licochalcone A,(+)-catechin, and cinnamaldehyde, had strong binding activities with the core target proteins, such as MAPK1 and MAPK3. The results of animal experiments showed that compared with the model group, GGD significantly increase superoxide dismutase, decreased malondialdehyde, lactate dehydrogenase, and creatine kinase-MB, and reduced the area of myocardial infarction. HE staining and TEM results showed that GGD pretreatment restored the structure of cardiomyocytes and alleviated the pathological changes and ultrastructural damage of mitochondria in the model group. In addition, GGD significantly down-regulated the phosphorylation of c-Jun N-terminal kinase and p38 and up-regulate that of extracellular regulated kinases 1/2 in the myocardial tissue. The results suggested that GGD may exert the anti-MI/RI effect by regulating the MAPK signaling pathway via the synergistic effects of Cinnamomi Ramulus and Glycyrrhizae Radix et Rhizoma.

N-3 polyunsaturated fatty acids attenuate amyloid-beta-induced toxicity in AD transgenic Caenorhabditis elegans via promotion of proteasomal activity and activation of PPAR-gamma.

Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. A major pathological characteristic of AD brain is the presence of senile plaques composed of ß-amyloid (Aß), the accumulation of which induces toxic cascades leading to synaptic dysfunction, neuronal apoptosis, and eventually cognitive decline. Dietary n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for patients with early-stage AD; however, the mechanisms are not completely understood. In this study, we investigated the effects of n-3 PUFAs on Aß-induced toxicity in a transgenic AD Caenorhabditis elegans (C. elegans) model. The results showed that EPA and DHA significantly inhibited Aß-induced paralytic phenotype and decreased the production of reactive oxygen species while reducing the levels of Aß in the AD worms. Further studies revealed that EPA and DHA might reduce the accumulation of Aß by restoring the activity of proteasome. Moreover, treating worms with peroxisome proliferator-activated receptor (PPAR)-γ inhibitor GW9662 prevented the inhibitory effects of n-3 PUFAs on Aß-induced paralytic phenotype and diminished the elevation of proteasomal activity by n-3 PUFAs, suggesting that PPARγ-mediated signals play important role in the protective effects of n-3 PUFAs against Aß-induced toxicity.

Effect of dandelion root polysaccharide on the pasting, gelatinization, rheology, structural properties and in vitro digestibility of corn starch.

The influence of dandelion root polysaccharide (DRP) on the gelatinization properties and in vitro digestibility of corn starch was investigated. Pasting behaviors indicated that the addition of DRP led to an increase of the pasting temperature and a decrease of viscosity. Compared to native corn starch, the swelling power, solubility and content of amylose leaching were reduced as the DRP addition increased. Scanning electron microscopy (SEM) analysis showed that DRP was easily dispersed in the starchy matrix, and a more uniform structure was observed in corn starch/DRP pastes. Fourier transform infrared (FT-IR) and X-ray diffraction (XRD) analyses confirmed that the crystal shape of the corn starch gels was not changed and no new groups were produced with increasing DRP concentration. Moreover, DRP could improve the fluidity of the gelatinized corn starch and reduce its digestibility. These findings provided fundamental information about DRP's application in the whole processing of corn starch.

Characterization, antioxidant and immunomodulatory effects of selenized polysaccharides from dandelion roots.

The polysaccharide (DRP) was gained from dandelion roots by ultrasonic-assisted enzymatic extraction (UAEE) followed by two-step column purification. Then selenylation of DRP has been accomplished by HNO3-Na2SeO3 method. sDRP-1 and sDRP-2 with the selenium content of 170 ± 1.13 and 710 ± 4.00 µg/g were prepared for further structural characterization and bioactivity determination. DRP, sDRP-1, and sDRP-2 were composed of the same monosaccharides in different molar ratios, and the molecular weights of DRP, sDRP-1 and sDRP-2 were 8700, 7900, and 5600 Da, respectively. Fourier transform infrared (FT-IR) spectra confirmed that DRP, sDRP-1, and sDRP-2 possessed similar functional groups. The results of Congo red test, X-ray diffraction (XRD) and scanning electron microscopy (SEM) showed that DRP, sDRP-1, and sDRP-2 had no three helix structure, did not form single crystal, and all belonged to amorphous morphology. sDRP-1 and sDRP-2 possessed greater antioxidant activities in vitro than the native polysaccharide DRP. At the same time, the selenized polysaccharides showed better immunomodulatory ability and could be used as new-type immunoenhancer. The present conclusions provided theoretical basis for the new application of dandelion polysaccharides and the development of dandelion resources.