Geraniol relieves mycoplasma pneumonia infection-induced lung injury in mice through the regulation of ERK/JNK and NF-κB signaling pathways.

BACKGROUND: Pneumonia is a serious pediatric lung injury disease caused by Mycoplasma pneumoniae (M. pneumoniae) with increasing global prevalence every year. The WHO has reported that nearly 19% of children die due to pneumonia worldwide. OBJECTIVE: The present research was conducted to discover the ameliorative properties of geraniol against M. pneumoniae-provoked pneumonia in mice through the modulation of inflammatory responses. METHODOLOGY: The pneumonia was provoked in the male Swiss albino mice via infecting animals with 100 µl of M. pneumoniae for 2 days and supplemented concurrently with 20 mg/kg of geraniol for 3 days. 100 mg/kg of azithromycin was used as a standard drug. The nitric oxide (NO) level and MPO activity were measured using kits. The SOD activity, GSH, and MDA levels were studied using standard methods. The polymerase chain reaction (PCR) study was performed to examine the M. pneumoniae DNA load. The inflammatory cytokines status was assessed by assay kits. The ERK1/2, JNK1/2, and NF-κB expressions were studied by reverse-transcription (RT-PCR). The lung tissues were analyzed microscopically to investigate the histological alterations. RESULTS: Geraniol treatment effectively reduced lung weight, NO level, and MPO activity in the pneumonia mice. The total cells and M. pneumoniae DNA load were also decreased by the geraniol. The SOD activity and GSH level were improved and MDA was decreased by the geraniol treatment. The IL-1, IL-6, IL-8, TNF-α, and TGF status were appreciably depleted by the geraniol in the pneumonia mice. Geraniol also suppressed the ERK1/2 and NF-κB expressions in the lung tissues. Histological findings also suggest the therapeutic roles of geraniol against pneumonia in mice. CONCLUSION: In summary, our results proved the beneficial roles of geraniol against the M. pneumoniae-provoked pneumonia. Geraniol could be a hopeful therapeutic agent to treat pneumonia in the future.

Aconitine Induces TRPV2-Mediated Ca2+ Influx through the p38 MAPK Signal and Promotes Cardiomyocyte Apoptosis.

Aconitine is the main effective component of traditional Chinese medicine Aconitum, which has been proved to have severe cardiovascular toxicity. The toxic effect of aconitine on cardiomyocytes is related to intracellular calcium overload, but the mechanism remains unclear. The aim of this study was to explore the mechanism of aconitine inducing intracellular Ca2+ overload and promoting H9c2 cardiomyocyte apoptosis through transient receptor potential cation channel subfamily V member 2 (TRPV2). After treated with different concentrations of aconitine, the level of cell apoptosis, intracellular Ca2+, and expression of p-p38 MAPK and TRPV2 of H9c2 cardiomyocytes were detected. The results showed that aconitine induced Ca2+ influx and H9c2 cardiomyocyte apoptosis in a dose-dependent manner and promoted p38 MAPK activation as well as TRPV2 expression and plasma membrane (PM) metastasis. siTRPV2, tranilast, and SB202190 reversed intracellular Ca2+ overload and H9c2 cardiomyocyte apoptosis induced by aconitine. These results suggested that aconitine promoted TRPV2 expression and PM metastasis through p38 MAPK signaling, thus inducing intracellular Ca2+ overload and cardiomyocyte apoptosis. Furthermore, TRPV2 is a potential molecular target for the treatment of aconitine poisoning.

Renal Tissue Damage Induced by Acute Kidney Injury in Sepsis Rat Model Is Inhibited by Cynaropicrin via IL-1ß and TNF-α Down-Regulation.

Acute kidney injury (AKI), one of the frequently diagnosed and serious sepsis induced complication has high morbidity and mortality. The present study investigated the effect of cynaropicrin on AKI induced pathological damage in rat model in vivo. Treatment with cynaropicrin suppressed AKI induced urea nitrogen and creatinine in the rat serum in dose-dependent manner. Development of sepsis mediated renal injury in rats was also effectively prevented on treatment with cynaropicrin. Secretion of AKI-induced IL-1ß and TNF-α in renal tissues was alleviated significantly in rats by cynaropicrin treatment. Additionally, in cynaropicrin-treated rats renal tissues AKI induced Bax expression was alleviated while as Bcl-2 was promoted compared to AKI rats. Cynaropicrin treatment improved the survival rate of the rats with AKI. Cynaropicrin inhibits renal tissue damage and increase survival rate in AKI rat model. The mechanism involves alleviation of inflammatory cytokine secretion and promotion of Bcl­2 expression. Thus, cynaropicrin may be used as therapeutic agent for treatment of AKI.

Thal protects against paraquat-induced lung injury through a microRNA-141/HDAC6/IκBα-NF-κB axis in rat and cell models.

The protective functions of thalidomide in paraquat (PQ)-induced injury have been reported. But the mechanisms remain largely unknown. In this research, a PQ-treated rat model was established and further treated with thalidomide. Oedema and pathological changes, oxidative stress, inflammation, fibrosis and cell apoptosis in rat lungs were detected. A PQ-treated RLE-6TN cell model was constructed, and the viability and apoptosis rate of cells were measured. Differentially expressed microRNAs (miRNAs) after thalidomide administration were screened out. Binding relationship between miR-141 and histone deacetylase 6 (HDAC6) was validated. Altered expression of miR-141 and HDAC6 was introduced to identify their involvements in thalidomide-mediated events. Consequently, thalidomide administration alone exerted no damage to rat lungs; in addition it reduced PQ-induced oedema. The oxidative stress, inflammation and cell apoptosis in rat lungs were reduced by thalidomide. In RLE-6TN cells, thalidomide increased cell viability and decreased apoptosis. miR-141 was responsible for thalidomide-mediated protective events by targeting HDAC6. Overexpression of HDAC6 blocked the protection of thalidomide against PQ-induced injury via activating the IkBα-NF-κB signalling pathway. Collectively, this study evidenced that thalidomide protects lung tissues from PQ-induced injury through a miR-141/HDAC6/IkBα-NF-κB axis.