Network Pharmacology Study of Bioactive Components and Molecular Mechanisms of the Glycoside Fraction from Picrorhiza scrophulariiflora Against Experimental Colitis.

Purpose: To explore the potential mechanism of glycosidic fraction of Picrorhiza scrophulariiflora Pennell (GPS) extract for the treatment of colitis using UPLC-QTOF-MS analysis, network pharmacology and experimental research. Methods: The active components of GPS extract were identified by UPLC-QTOF-MS analysis and extracted their targets from the databases, which was used for network pharmacology analysis. Kyoto Encyclopedia of genes and genomes (KEGG) pathway analysis was performed to discover potential therapeutic mechanisms, and the network pharmacology results were then validated by in vivo and in vitro experiments. Results: The results showed that GPS extract significantly alleviated the clinical signs of colitis, including body weight, disease activity index, colon shortening, and colon tissue damage, and inhibited the transcription and production of colonic IL-1ß and IL-6 in DSS-induced colitis mice. In vitro, GPS extract also significantly suppressed nitric oxide (NO) production, iNOS expression, IL-1ß and IL-6 transcription of LPS-activated RAW 264.7 cells. Network pharmacology integrated with experimental validation identified that GPS extract significantly suppressed Akt, p38, ERK, and JNK phosphorylation in vivo and in vitro, and luteolin, apocynin, caffeic acid, caffeic acid methyl ester, luteoloside, picroside II, aucubin, cinnamic acid, vanillic acid, and sweroside were the main components responsible for the anti-inflammatory effect of GPS. These findings demonstrate that the potential anti-inflammatory effect of GPS extract against colitis is achieved through suppressing PI3K/Akt and MAPK pathways, and that the abovementioned active components mainly exerted its anti-inflammatory effect. Conclusion: The therapeutic effect of GPS extract on colitis is related to PI3K/Akt and MAPK pathways, which is a promising remedy for colitis therapy.

Protective Effect of Simplicillium sp. Ethyl Acetate Extract against High Glucose-Induced Oxidative Stress in HUVECs.

This study aimed at investigating the cytoprotective effect of an ethyl acetate extract of insect fungi against high glucose- (HG-) induced oxidative damage in human umbilical vein endothelial cells (HUVECs). An insect fungus strain termed CH180672 (CH) was found for protecting HUVECs from HG-induced damage. In this study, CH was identified as Simplicillium sp. based on a phylogenetic analysis of ITS-rDNA sequences. Ethyl acetate extract (EtOAc) of this strain (CH) was subjected to the following experiments. Cell viability was examined with the MTT method. To evaluate the protection of CH, intracellular reactive oxygen species (ROS), malondialdehyde (MDA) levels, and the activities of antioxidant enzymes were measured and the expression of oxidation-associated proteins was assessed. In the current study, it has been found that CH can increase the survival rate of HUVECs induced by HG. Additionally, we found that HG-induced nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) signal decreased and increased the intracellular ROS and MDA generation in HUVECs. However, CH treatment strongly promoted the translocation of Nrf2 and its transregulation on HO-1 and ultimately inhibited the high level of ROS and MDA induced by HG. The regulatory ability of CH was similar to Nrf2 agonist bardoxolone, while the effect was abolished by ML385, suggesting that Nrf2 mediated the inhibition of CH on HG-induced oxidative stress in HUVECs. Taken together, CH can improve HG-induced oxidative damage of HUVECs, and its mechanism may be related to the regulation of the Nrf2/HO-1 pathway.

Salvianolic Acid B-Alleviated Angiotensin II Induces Cardiac Fibrosis by Suppressing NF-κB Pathway In Vitro.

BACKGROUND Salvianolic acid B (SalB) is the representative component of phenolic acids derived from the roots and rhizomes of Salvia miltiorrhiza Bge (Labiatae), which has been used widely in Asian countries for clinical therapy of various cardiovascular dysfunction-related diseases. However, cardiac protection effects and the underlying mechanism for clinical application are still poorly understood. Here, we investigated the potential anti-myocardial fibrosis effect and mechanism of SalB on Angiotensin II (Ang II)-induced cardiac fibrosis in vitro. MATERIAL AND METHODS The proliferation and migration capacity of cardiac fibroblasts (CFBs) were measured by MTT assay and scratch analysis, respectively. The colorimetric assay determined the hydroxyproline content in medium. Western blotting detected the protein expressions of nuclear transcription factor-kappa B (NF-κB) pathway-associated proteins, fibronectin (FN), collagen type I (Coll I), α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF). The expression of α-SMA protein was observed by immunofluorescence staining. qRT-PCR detected the mRNA expression of NF-κB. RESULTS SalB attenuated Ang II-induced the proliferation and the migration ability of CFBs. Ang II-induced the extracellular matrix protein Coll I, FN, and α-SMA, the pro-fibrotic cytokine CTGF protein expression was inhibited, and the nuclear translocation of NF-κB p65 subunit was reduced by SalB. Western blotting and qRT-PCR confirmed that SalB blocked the activation of NF-κB induced by Ang II. PDTC (the NF-κB inhibitor) also inhibited proliferation of CFBs and reduced α-SMA and Coll I expression induced by Ang II. CONCLUSIONS SalB can alleviate Ang II-induced cardiac fibrosis via suppressing the NF-κB pathway in vitro.

[RAPD analysis on the germplasm resources of Gastrodia elata in Guizhou].

Genetic polymorphisms of genomic DNA of 15 samples from wild and culturaled Gastrodia elata Blume in Guizhou were analyzed by RAPD method. 12 effective primers are screened from 40 primers amplified a total number of 93 loci, among which 66 are polymorphic and the percentage of polymorphic loci (PPB) is 70.97%. UPGMA dendrogram analyzed by NTSYSpc, ver. 2.2 shows that Gastrodia elata have apparent genetic variance. Geological distribution and growing environment were significant factors for the polymorphism.