The cover image is based on the RESEARCH ARTICLE Acacia catechu (L.f.) Willd and Scutellaria baicalensis Georgi extracts suppress LPS-induced pro-inflammatory responses through NF-кB, MAPK, and PI3K-Akt signaling pathways in alveolar epithelial type II cells by Tian Feng et al., https://doi.org/10.1002/ptr.6499.
Acacia catechu (L.f.) Willd (ACW) and Scutellaria baicalensis Georgi (SBG) are one of the most famous couplet Chinese medicines, widely used for treating infantile cough, phlegm, and fever caused by pulmonary infection. However, the underlying molecular mechanism of their anti‐inflammatory activity has not been determined. The aim of this study was to evaluate the protective effect of this couplet Chinese medicines (ACW‐SBG) on lipopolysaccharide (LPS)‐induced inflammatory responses in acute lung injury (ALI) model of rats and the potential molecular mechanisms responsible for anti‐inflammatory activities in alveolar epithelial type II cells (AEC‐II). Standardization of the 70% ethanol extract of ACW and SBG was performed by using a validated reversed‐phase high‐pressure liquid chromatography method. Rats were pretreated with ACW‐SBG for 7 days prior to LPS challenge. We assessed the effects of ACW‐SBG on the LPS‐induced production of tumor necrosis factor alpha (TNF‐α) and interleukin 1 beta (IL‐1β) in the bronchoalveolar lavage fluid (BALF). The wet‐to‐dry weight ratio was calculated, and hematoxylin and eosin staining of lung tissue was performed. Cell viability of AEC‐II was measured by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Real‐time quantitative reverse transcription polymerase chain reaction assay was carried out to quantify the relative gene expression of TNF‐α and IL‐1β in AEC‐II. The western blotting analysis was executed to elucidate the expression of mediators linked to nuclear factor‐kappa B (NF‐κB), mitogen‐activated protein kinase (MAPK), and phosphatidylinositol‐3 kinase‐protein kinase B (PI3K‐Akt) signaling pathways. ACW‐SBG significantly decreased lung wet‐to‐dry weight ratio, ameliorated LPS‐induced lung histopathological changes, and reduced the release of inflammatory mediators such as TNF‐α and IL‐1β in BALF. In AEC‐II, we found that the expression of TNF‐α mRNA was also inhibited by ACW‐SBG. ACW‐SBG blocked NF‐κB activation by preventing the phosphorylation of NF‐κB (p65) as well as the phosphorylation and degradation of the inhibitor of kappa B kinase. ACW‐SBG extracts also inhibited the phosphorylation of respective MAPKs (c‐Jun N‐terminal kinase, extracellular signal‐regulated kinase, and p38) as well as Akt. The present study demonstrated that ACW‐SBG played a potent anti‐inflammatory role in LPS‐induced ALI in rats. The potential molecular mechanism was involved in attenuating the NF‐κB, MAPKs, and PI3K‐Akt signaling pathways in LPS‐induced AEC‐II.
Abstract Background: As the commonest form of ischemic heart diseases, the Myocardial Ischemia-Reperfusion injury (MI/RI) accounts for almost 50 percent of all deaths. The prevention and treatment of MI/RI while reducing the mortality of myocardial infarction has become a raging topic of research in the cardiovascular field. At present, there are no effective drugs for the treatment of MI/RI. Hence, it becomes imperative to identify or develop efficient lead compounds for treating MI/RI. It has been reported that the Ganjiang Fuzi Decoction (GFD) could be used for the effective treatment of MI/RI due to its promotion of vasodilation and vascular endothelial cell proliferation besides reducing the oxidative damage. Methods: The network pharmacological methods were used in this study, for analyzing the biological processes and the molecular mechanisms of the GFD for MI/RI treatment. In vitro and in vivo experiments were performed for verification of the results of the network pharmacological predictions. Results: Around 16 active components of GFD were discovered against MI/RI, where aconitine, 6-ginger, mesaconitine, and hypaconitine were the leading ones with regard to the degree value. Moreover, it was found that 88 MI/RI-related targets mainly involved six aspects, apoptosis, oxidative stress, inflammation, mitochondrial energy metabolism, and vasodilation. In vitro studies indicated the ability of the GFD to increase the survival rate, decrease the apoptosis rate, reduce oxidative damage, and increase the expression of HIF-1α, VEGF, and eNOS in hypoxia/reoxygenation(H/R) injured Rat Vascular Endothelial Cells (RVEC). The in vivo studies illustrated the capacity of the GFD to reduce the myocardial tissue damage and the infarction area, while increasing the expression of HIF-1α, VEGF, and eNOS in the MI/RI rats. Conclusions: The results of this study confirmed the anti-MI/RI role of the GFD through the activation of the HIF-1α signaling pathway, promotion of vascular proliferation and dilation, and the reduction in oxidative damage. The findings of this study would further provide experimental evidence for the application of the GFD in the treatment of MI/RI.
Aim: A sensitive and reliable LC-MS/MS method has been established and validated to the quantitation of rivaroxaban (RIV) and TAK-438 in rat plasma using carbamazepine as internal standard. Results: The procedure of method validation was conducted according to the guidelines of EMA and US FDA. At the same time, the method was applied to pharmacokinetic interactions study between RIV and TAK-438 for the first time. When RIV and TAK-438 co-administration to rats, main pharmacokinetic parameters of TAK-438 like AUC(0-t), AUC(0-∞) and Cmax had statistically significant increase. The main pharmacokinetic parameters of RIV have no statistically significant difference (p > 0.05) when co-administered except for t1/2 (p < 0.01). Conclusion: The results indicated that drug-drug interactions occurred between RIV and TAK-438 when co-administered to rats.
Aim: A reliable, sensitive and simple LC–MS/MS method has been established and validated for the quantitation of rivaroxaban (RIV) and metformin (MET) in rat plasma. Results: The procedure of method validation was conducted according to the guiding principles of EMA and US FDA. At the same time, the method was applied to pharmacokinetic interactions study between RIV and MET for the first time. When RIV and MET coadministered to rats, pharmacokinetic parameters of MET like AUC(0-t), AUC(0-∞) and Cmax had statistically significant increased. tmax of RIV was prolonged without affecting t1/2 obviously and Cmax was inhibited significantly (p < 0.05) by comparison to the single group. Conclusion: The results indicated that drug–drug interactions occurred when the coadministration of RIV and MET.
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