Saponins from Allium macrostemon Bulbs Attenuate Endothelial Inflammation and Acute Lung Injury via the NF-κB/VCAM-1 Pathway.

Endothelial inflammation is a multifaceted physiological process that plays a pivotal role in the pathogenesis and progression of diverse diseases, encompassing but not limited to acute lung infections like COVID-19, coronary artery disease, stroke, sepsis, metabolic syndrome, certain malignancies, and even psychiatric disorders such as depression. This inflammatory response is characterized by augmented expression of adhesion molecules and secretion of pro-inflammatory cytokines. In this study, we discovered that saponins from Allium macrostemon bulbs (SAMB) effectively inhibited inflammation in human umbilical vein endothelial cells induced by the exogenous inflammatory mediator lipopolysaccharide or the endogenous inflammatory mediator tumor necrosis factor-α, as evidenced by a significant reduction in the expression of pro-inflammatory factors and vascular cell adhesion molecule-1 (VCAM-1) with decreased monocyte adhesion. By employing the NF-κB inhibitor BAY-117082, we demonstrated that the inhibitory effect of SAMB on VCAM-1 expression may be attributed to the NF-κB pathway's inactivation, as characterized by the suppressed IκBα degradation and NF-κB p65 phosphorylation. Subsequently, we employed a murine model of lipopolysaccharide-induced septic acute lung injury to substantiate the potential of SAMB in ameliorating endothelial inflammation and acute lung injury in vivo. These findings provide novel insight into potential preventive and therapeutic strategies for the clinical management of diseases associated with endothelial inflammation.

Edgeworthia gardneri (Wall.) Meisn. Ethanolic Extract Attenuates Endothelial Activation and Alleviates Cardiac Ischemia-Reperfusion Injury.

Endothelial pro-inflammatory activation is pivotal in cardiac ischemia-reperfusion (I/R) injury pathophysiology. The dried flower bud of Edgeworthia gardneri (Wall.) Meisn. (EG) is a commonly utilized traditional Tibetan medicine. However, its role in regulating endothelium activation and cardiac I/R injury has not been investigated. Herein, we showed that the administration of EG ethanolic extract exhibited a potent therapeutic efficacy in ameliorating cardiac endothelial inflammation (p < 0.05) and thereby protecting against myocardial I/R injury in rats (p < 0.001). In line with the in vivo findings, the EG extract suppressed endothelial pro-inflammatory activation in vitro by downregulating the expression of pro-inflammatory mediators (p < 0.05) and diminishing monocytes' firm adhesion to endothelial cells (ECs) (p < 0.01). Mechanistically, we showed that EG extract inhibited the nuclear factor kappa-B (NF-κB), c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways to attenuate EC-mediated inflammation (p < 0.05). Collectively, for the first time, this study demonstrated the therapeutic potential of EG ethanolic extract in alleviating I/R-induced inflammation and the resulting cardiac injury through its inhibitory role in regulating endothelium activation.

Edgeworthia gardneri (Wall.) Meisn. extract protects against myocardial infarction by inhibiting NF-κB-and MAPK-mediated endothelial inflammation.

Background: Experimental and clinical evidence has demonstrated a pivotal role of inflammation in the pathogenesis of ischemic heart disease, and targeting inflammation has been shown to provide clinical benefits for patients with coronary disease. Endothelial cells constitute the majority of non-cardiomyocytes in the heart. Endothelial pro-inflammatory activation is recognized as a critical component in the pathophysiology of cardiovascular disease. The dried flowers of Edgeworthia gardneri (Wall.) Meisn. (EG) have been widely used as Tibetan folk medicine to ameliorate a range of metabolic disorders, such as diabetes mellitus, hyperlipidemia, hypertension, and obesity. However, its role in modulating endothelial inflammation and ischemic heart disease has not been evaluated. Methods and results: Herein, using a preclinical rat model of coronary artery ligation-induced myocardial infarction (MI), we demonstrated that systemic administration of EG extract (EEEG) attenuated ischemic cardiac injury. EEEG reduced myocardial infarct size, improved cardiac function, and ameliorated adverse cardiac remodeling. Moreover, the cardioprotective effects of EEEG were associated with decreased MI-induced myocardial inflammation. Consistent with the anti-inflammatory role of EEEG in vivo, EEEG attenuated TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) activation and monocyte-endothelial cell firm adhesion in vitro. Mechanistically, our data showed that EEEG's mode of action suppresses the activation of NF-κB, ERK, and p38 MAPK signaling pathways in ECs. Importantly, we demonstrated that EEEG inhibits endothelial inflammation in an NF-κB- and p38 MAPK-dependent manner using pharmacological inhibitors. Conclusion: Collectively, this study identified EG as a potential therapeutic agent in attenuating endothelial inflammation and managing ischemic cardiovascular disease.

Effectiveness and safety of traditional Chinese medicines for non-alcoholic fatty liver disease: Protocol for systematic review and meta-analysis.

BACKGROUND: Previous reviews indicate that the effect of Traditional Chinese medicines (TCM) on non-alcoholic fatty liver disease (NAFLD) remains uncertainty. The study results published in the past 8 years may change this situation, but there is no updated systematic review. Therefore, we designed this study to systematically evaluate the effectiveness and safety of TCM in the treatment of NAFLD. METHODS AND ANALYSIS: We will search nine online databases from inception to October 01 2019, and the language will not be restricted on included trials. Randomized controlled trials that included patients with NAFLD receiving TCM therapy versus a control group will be included. Two researcher will perform independently the selection of studies, risk of bias assessment and data extraction. We will use the RevMan V.5.2 software with fixed effects model or random effects model according to the heterogeneity test to conduct the data synthesis. We will present the dichotomous data and the continuous data with risk ratios with 95% CIs and weighted mean differences or standardized mean differences with 95% CIs. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system will be used to evaluate the evidence quality with low risk, unclear risk, and high risk. RESULTS: This study will demonstrate an evidence-based review of TCM for NAFLD. CONCLUSION: The study will provide clear evidence to assess the effectiveness and side effects of TCM for NAFLD.