Background and Purpose: Septic cardiomyopathy, which is one of the features of multi-organ dysfunction in sepsis, is characterized by ventricular dilatation, reduced ventricular contractility, and reduction in ejection fraction and, if severe, can lead to death. To date, there is no specific therapy that exists, and its treatment represents a large unmet clinical need. Herein, we investigated the effects and underlying anti-inflammatory mechanisms of hydrogen gas in the setting of lipopolysaccharide (LPS)-induced cardiomyocytes injury. Experimental Approach: Hydrogen gas was intraperitoneally injected to mice in LPS plus hydrogen group and hydrogen group for 4 days. On fourth, LPS was given by intraperitoneal injection to mice in LPS group and to mice in LPS plus hydrogen group. In addition, H9c2 cardiomyocytes were treated with hydrogen-rich medium for 30 min before LPS. The transthoracic echocardiography was performed at 6 h post‐LPS to assess left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (EF%), fractional shortening (FS%), left ventricular mass average weight (LV mass AW), and LV mass AW (Corrected). The histological and morphological analyses of left ventricular were performed by hematoxylin and eosin (H&E) staining and Masson’s trichrome staining. The mRNA levels of ANP and BNP were examined by PCR in vitro . The expression of cytokines were assayed by Enzyme Linked Immunosorbent Assay (ELISA) and PCR. Moreover, Western blotting was performed to examine the expression of TLR4, the activation of ERK1/2, p38, JNK, and the expression of NF-κB in nucleus after 6 h of LPS challenge in vivo and in vitro . Key Results: LPS induced cardiac dysfunction; hydrogen therapy improved cardiac function after LPS challenge. Furthermore, pretreatment with hydrogen resulted in cardioprotection during septic cardiomyopathy via inhibiting the expression of pro-inflammatory cytokines TNFα, IL-1β, and IL-18; suppressing the phosphorylation of ERK1/2, p38, and JNK; and reducing the nuclear translocation of NF-κB and the expression of TLR4 by LPS. Conclusion and Implications: Hydrogen therapy prevents LPS-induced cardiac dysfunction in part via downregulation of TLR4-mediated pro-inflammatory cytokines expression.

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Objective: To investigate effects of Cornus officinalis Total Glycosides (COTG) and Cornus Polysaccharide (CP) on myocardial protection and on expression of mitochondria biogenesis related gene of acute myocardial infarction (AMI) rats, Materials and Methods: Ninety-six SD rats of SPF level were randomly divided into 5 groups: sham operation group, model group, preventive treatment group, COTG treatment group, CP treatment group, and there were 12 cases in each one. By legating the left anterior descending branch of coronary artery method, acute myocardial infarction model was established. The rat of sham operation group and model group was intragastric administered with physiological saline; other groups were given with corresponding drugs. The cardiac function, the myocardial infarct area, the expression of mitochondrial biogenesis genes such as PGC-1α, PGC-1β, NRF-1mRNA and GSK-3β mRNA, GSK-3β Protein Expression were analyzed. Results: The results revealed that compared with model group, myocardial infarction size, LVDs, LVDd, LVESV, LVEDP, and −dp/dt decreased; LVSP increased in preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05); LVEDV increased in preventive treatment group (p < 0.05), PGC 1 alpha, and PGC 1 beta; the NRF-1 mRNA expression increased in preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05). Compared with CP and COTG treatment group, PGClpha, beta PGC 1, the NRF-1 mRNA expression increased in preventive treatment group (p < 0.05). Compared with the sham operation group, GSK-3 beta mRNA and protein expression increased in model group, preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05). Compared with model group, GSK-3 beta mRNA expression reduced in preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05). Conclusions: Cornus officinalis total glycosides and Cornus polysaccharides can effectively * Corresponding author. K. Chen et al. 46 protect myocardial mitochondria of acute myocardial infarction rats by activating GSK-3β signaling pathways, and reduce the myocardial infarct size, which has great significance for improving cardiac function.

Objective: To investigate the mechanism of Cornus officinalis Total Glycosides (COTG) on myocardial protection, by studying effects of COTG on cardiomyocyte apoptosis induced by hypoxia/reoxygenation and calcium concentration in rats. Methods: The myocardial cells of born 1-3d SD rats were isolated by enzyme digestion, cultured for 3 days. Cells were divided into five groups: Control group, H/R group, Cornus officinalis Total Glycosides low-dose group (LDG), Cornus officinalis Total Glycosides middle-dose group (MDG) and Cornus officinalis Total Glycosides high-dose group (HDG). Three drug groups were pretreated with different doses of Cornus officinalis Total Glycosides before hypoxia/reoxygenation treatment. The apoptotic rate was determined by flow cytometry assay, the intracellular free calcium concentration was examined by flow cytometry, and the ultrastructure of myocardial cells was observed under transmission electron microscope. Results: The results revealed that Cornus officinalis Total Glycosides pretreatment decreased apoptosis rate, but the effect of lower dosage is not significant. Furthermore, Cornus officinalis Total Glycosides can attenuate mitochondrial calcium overload, improve mitochondrial morphology and inhibit cardiomyocyte apoptosis caused by H/R. Conclusion: Cornus officinalis Total Glycosides pretreatment can inhibit cardiomyocyte apoptosis and calcium overload during H/R injury. However, the underlying mechanisms require us to further study.