Diabetic cardiomyopathy, especially myocardial ischemia reperfusion (I/R) injury, is a major cause of morbidity and mortality in type 2 diabetic patients. The increasing of basal p38 MAP Kinase (p38 MAPK) activation is a major factor that aggravates cardiac death on diabetic cardiomyopathy. In addition, metformin also shows cardio-protective effects on myocardial ischemia/reperfusion injury. In this study, we investigated the effect of the combination between metformin and p38 MAPK inhibitor (SB203580) in diabetic rats subjected to I/R injury. H9c2 cells were induced into a hyperglycemic condition and treated with metformin, SB203580 or the combination of metformin and SB203580. In addition, cells in both the presence and absence of drug treatment were subjected to simulated ischemia/reperfusion injury. Cell viability and cellular reactive oxygen species (ROS) were determined. Moreover, the Goto-Kakizaki (GK) rats were treated with metformin, SB203580, and the combination of metformin and SB203580 for 4 weeks. Diabetic parameters and cardiac functions were assessed. Finally, rat hearts were induced ischemia/reperfusion injury for the purpose of infarct size analysis and determination of signal transduction. A high-glucose condition did not reduce cell viability but significantly increased ROS production and significantly decreased cell viability after induced sI/R. Treatment using drugs was shown to reduce ROS generation and cardiac cell death. The GK rats displayed diabetic phenotype by increasing diabetic parameters and these parameters were significantly decreased when treated with drugs. Treatment with metformin or SB203580 could significantly reduce the infarct size. Interestingly, the combination of metformin and SB203580 could enhance cardio-protective ability. Myocardial I/R injury significantly increased p38 MAPK phosphorylation, Bax/Bcl-2 ratio and caspase-3 level. Treatment with drugs significantly decreased the p38 MAPK phosphorylation, Bax/Bcl-2 ratio, caspase-3 level and increased Akt phosphorylation. In conclusion, using the combination of metformin and SB203580 shows positive cardio-protective effects on diabetic ischemic cardiomyopathy.

Artemisia lactiflora, a Chinese-origin plant, has been reported to have unique phytochemicals responsible for its medicinal properties. The growth of the agricultural industry emits air pollution, which has adverse effects on health. There are limited scientific reports on the biological activities of A. lactiflora. Studies on its activities and mechanisms may provide insight into its use in medicinal purposes to treat those health problems and conditions. In this study, leaves of A. lactiflora were extracted and fractioned with solvents of different polarities. Total phenolics, total flavonoids DPPH• scavenging, ABTS•+ scavenging, and cytotoxicity of A. lactiflora were assessed. Anti-inflammatory activities were evaluated by pre-treating macrophages with extract or fractions then induced inflammatory response by coconut shell pyrolysis smoke. Inflammatory responses were assessed by measuring pro-inflammatory genes expression and pro-inflammatory cytokines secretion. Among all extract and fractions of A. lactiflora, butanol fraction has the highest phenolic, flavonoid, and DPPH• scavenging activity. All extract and fractions significantly down-regulated pro-inflammatory genes expression ( RelA, TNF, IL6) and decreased pro-inflammatory cytokines secretion (TNF-α, IL-6), p < 0.0001, compared with pyrolysis smoke-induced macrophages. The ethyl acetate fraction showed the highest anti-inflammatory activity in decreasing pro-inflammatory cytokines secretion. These results may prove the anti-inflammatory activities of A. lactiflora through the inhibition of the NF-κB-dependent pathway. Taken together, this study first reported the anti-inflammatory activities of A. lactiflora. Thus, the plant can be used to prevent and treat inflammatory responses caused by highly oxidative pyrolysis smoke released from the re-utilization of agro-industrial leftovers.

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Background: Sepsis is a progressive inflammatory response with serious condition and high mortality rate. Gram-negative bacteria are the most common pathogens that cause inflammatory sepsis by promoting the release of pro-inflammatory cytokines via the activation of NF-κB-dependent pathway. Severe sepsis can cause cardiac dysfunction and increases the chance of death. Artemisia lactiflora is a Chinese-origin medicinal plant that contains phenolics and flavonoids with probable anti-inflammatory activities. Therefore, the purpose of this study was to investigate the anti-inflammatory activity of A. lactiflora leaves extract on a cardiac sepsis model. Methods: Leaves of A. lactiflora were extracted and fractioned with solvents of different polarities. The cytotoxicity of extract and fractions was evaluated and calculated by neutral red assay and curve fitting analysis. Sepsis condition of cardiomyoblasts (H9c2) was stimulated with live culture of Escherichia coli (O157:H7). Anti-inflammatory activity of A. lactiflora was observed by treating cardiomyoblasts with the extract and fractions in the presence of E. coli. Expression of pro-inflammatory genes (TNF, IL6) and secretion of pro-inflammatory cytokines (TNF-α, IL-6) were measured by RT-qPCR and ELISA. Results: Co-treatment of A. lactiflora extract and all fractions significantly downregulated expression of TNF and IL6 as well as decreased secretion of TNF-α and IL-6, p < 0.0001, compared with E. coli-stimulated cardiomyoblasts. The butanol fraction had the highest potency in reducing pro-inflammatory cytokines secretion of cardiomyoblasts under sepsis condition. As a result, A. lactiflora leaves extract demonstrated therapeutic potential in the cardiac sepsis model by alleviating inflammatory response. The plant can potentially be developed as an alternative medicine for inflammation and sepsis.

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