Chloranthalactone B (CTB), a lindenane-type sesquiterpenoid, was obtained from the Chinese medicinal herb Sarcandra glabra, which is frequently used as a remedy for inflammatory diseases. However, the anti-inflammatory mechanisms of CTB have not been fully elucidated. In this study, we investigated the molecular mechanisms underlying these effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. CTB strongly inhibited the production of nitric oxide and pro-inflammatory mediators such as prostaglandin E2, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 in RAW264.7 cells stimulated with LPS. A reverse-transcription polymerase chain reaction assay and Western blot further confirmed that CTB inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, and IL-1β at the transcriptional level, and decreased the luciferase activities of activator protein (AP)-1 reporter promoters. These data suggest that inhibition occurred at the transcriptional level. In addition, CTB blocked the activation of p38 mitogen-activated protein kinase (MAPK) but not c-Jun N-terminal kinase or extracellular signal-regulated kinase 1/2. Furthermore, CTB suppressed the phosphorylation of MKK3/6 by targeting the binding sites via formation of hydrogen bonds. Our findings clearly show that CTB inhibits the production of inflammatory mediators by inhibiting the AP-1 and p38 MAPK pathways. Therefore, CTB could potentially be used as an anti-inflammatory agent.
Coronary heart disease (CHD) has become one of the leading causes of death and functional impairment in the world. Hyperglycemia is associated with an increased risk of cardiovascular disease. It was speculated that miRNAs in peripheral blood were a primary parameter in discriminating CHD. The biological characteristics of coronary heart disease with hyperglycemia (HCHD) and coronary heart disease with euglycemia (ECHD) were investigated in the study. Circulating miRNAs from 26 HCHD patients and 42 ECHD patients were identified by microarrays. Compared with the healthy patients, 15 and 20 differentially expressed miRNAs were identified in HCHD and ECHD groups, respectively. Gene ontology analysis was carried out by DAVID and functional annotations of the miRNA targets related to ATP binding, cellular components, protein binding, RNA binding, DNA binding, and so on. KEGG database was used for pathway analysis. Eleven pathways were identified in both HCHD and ECHD groups. Furthermore, 13 and 3 pathways were only identified in HCHD or ECHD group, respectively. And then, miRNA-gene regulatory networks were constructed to study the relationship between differentially expressed miRNAs and genes. This suggested that hsa-let-7c-5p and hsa-miR-24-3p might have the most important function for hyperglycemia in coronary heart disease patients.
1 September 2020 in Bioinorganic Chemistry and Applications
Angelica gigas Nakai (AGN) was first processed by ultrafine grinding technology and hot-melt extrusion (HME). The potential antioxidant and anti-inflammatory activities of AGN with a different process were compared, and the effect on the human Kv1.3 potassium channel was detected. The process of ultrafine powderization on AGN significantly increased the total phenolic and flavonoid contents, antioxidant activity, and DNA damage protective effect. On the contrary, AGN solid dispersion (AGN-SD) based on Soluplus® showed the highest inhibitory effect on NO production and the human Kv1.3 channel. In addition, AGN-SD inhibited the production of prostaglandin E2 and intracellular reactive oxygen species and the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, interleukin 1β, and interleukin 6. Taken together, these results suggest that ultrafine powderization and solid dispersion formation via HME can significantly improve the biological activities of AGN. The results also suggested that ultrafine powderization and HME may be developed and applied in the pharmaceutical industry.
1 January 2018 in Evidence-Based Complementary and Alternative Medicine
Aging is closely connected with death, progressive physiological decline, and increased risk of diseases, such as cancer, arteriosclerosis, heart disease, hypertension, and neurodegenerative diseases. It is reported that moxibustion can treat more than 300 kinds of diseases including aging related problems and can improve immune function and physiological functions. The digital gene expression profiling of aged mice with or without moxibustion treatment was investigated and the mechanisms of moxibustion in aged mice were speculated by gene ontology and pathway analysis in the study. Almost 145 million raw reads were obtained by digital gene expression analysis and about 140 million (96.55%) were clean reads. Five differentially expressed genes with an adjusted P value < 0.05 and |log2(fold change)| > 1 were identified between the control and moxibustion groups. They were Gm6563, Gm8116, Rps26‐ps1, Nat8f4, and Igkv3‐12. Gene ontology analysis was carried out by the GOseq R package and functional annotations of the differentially expressed genes related to translation, mRNA export from nucleus, mRNA transport, nuclear body, acetyltransferase activity, and so on. Kyoto Encyclopedia of Genes and Genomes database was used for pathway analysis and ribosome was the most significantly enriched pathway term.