Analyzing the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells

Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells.Methods:This study used Xuefu Zhuyu decoction to intervene human umbilical vein endothelial cells incubated by hypertensive patients’serum,then detected the function of vascular endothelial cells.The aqueous extract of XFZY was analyzed and validated by liquid chromatography-mass spectrometry technology;Finally,macromolecular docking technology was used to analyze the potential active substances and targets of XFZY in the prevention and treatment of hypertension.Results:Compared with the model group,the XFZY group showed a significant increase in NO expression(P<0.01)and a significant decrease in ET-1 expression(P<0.001);and the expression of BIP,P-JNK,CHOP,and BAX in XFZY group cells was significantly decreased(P<0.001),while the expression of JNK and BCL2 was significantly increased(P<0.001).19 main compounds were identified in XFZY and there were 3 pairs of molecular complexes with high affinity for markers of the endoplasmic reticulum stress,including BIP-Hesperidin complex,BIP-HSYA complex and JNK-Naringin complex.Conclusion:This study analyzed the potential pharmacodynamic substance and targets of Xuefu Zhuyu decoction in improving the function of hypertensive vascular endothelial cells,which could provide a scientific basis for the future molecular mechanism of XFZY in treating hypertension.

Pharmacological induced target temperature management after cardiac arrest： the capsaicinoids

Cardiac or respiratory arrest lasting only a few minutes can inflict grave harm on numerous bodily organs, not least of all, the brain. Neurocognitive deficits, which are often severe and profoundly life altering, remain a major source of morbidity among survivors.

New trends in pharmacological treatment of acute kidney injury

Acute kidney injury,previously known as acute renal failure(AKI),is defined as an abrupt decrease in kidney function that occurs within hours or days.This new nomenclature opens a new door for possibility of treatment of developing renal injury before progression to unresolved renal failure.AKI arises due to diverse etiologic factors that rely mainly on three categories namely,prerenal,intrinsic renal,and post-renal factors with different clinical pictures,and confers a spectrum of injury ranging from mild to severe and sometimes leads to end-stage renal disease.Complexity of pathogenesis and other factors generate barriers to developing effective treatments despite a large number of experimental and clinical studies.In this review,recent advances in the potential of the currently used drugs for renoprotection,novel pharmacological targets,and prospective therapeutics for AKI are discussed.The information in this review was extracted from electronic resources(Pub Med,Google Scholar,Wiley,Science Direct,Springer),and English scientific books by using keywords including kidney,injury,recent therapy,and pharmacological targets.The articles were carefully checked for their relevance to the current manuscript.Recent targets of cellular repair or regenerative processes involved in AKI such as autophagy,ferroptosis inhibition,and p53 antagonism seem to be effective in disease control.This may help researchers and clinicians to understand how to target the interrelated molecular and cellular mechanisms underlying the pathogenesis of AKI.

Anti-hepatic carcinoma mechanisms of calycosin through targeting ferroptosis

Background Ferroptosis,a pathologic state induced by lipid-driven oxidative stress,is associated with the development of human cancers.Calycosin,a natural compound with antioxidant and anti-inflammatory activities,has promising antitumor effects.However,the ferroptosis-related mechanism of calycosin in the treatment of hepatic carcinoma has not been reported.Methods This study applied network pharmacology and bioinformatic approaches(including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis)to investigate the pharmacologic targets and mechanism of action of calycosin in the treatment of hepatic carcinoma through targeting ferroptosis.By searching online databases including The Cancer Genome Atlas,FerrDb,GeneCards,SwissTargetPrediction,SuperPred,BindingDB,TargetNet,BATMAN-TCM,and Drugbank,we identified 13 ferroptosis-related putative target genes of calycosin against hepatic carcinoma including IL-6,PTGS2,SRC,HRAS,NQO1,NOX4,PGK1,G6PD,GPI,MIF,NOS2,ALDOA,and SQSTM1.Results Molecular docking analysis revealed that calycosin potentially binded directly with the target proteins IL-6,PTGS2,and SRC.Functional enrichment analysis of these proteins indicated that they were involved in gluconeogenesis and apoptosis through regulation of ERK1,ERK2,and MAPK activities(P<0.05).Conclusion Calycosin exerts antitumor effects in hepatic carcinoma by targeting ferroptosis through regulation of IL-6,PTGS2,and SRC.

Exploring Traditional Chinese Medicine by A Novel Therapeutic Concept of Network Target

Traditional Chinese medicine（TCM） holds a holistic theory, and specializes in balancing disordered human body using numerous natural products, particularly Chinese herbal formulae. TCM has certain treatment advantages for patients suffering from various complex diseases. However, due to the complex nature of TCM, it remains difficult to unveil such holistic medicine by the current reductionism research strategies, which treat both herbal ingredients and targets in isolation. Recently, an emerging network pharmacology approach has been introduced to tackle this bottleneck problem. A TCM-derived novel therapeutic concept, ＂network target＂, which is different from the Western medicine＇s ＂onetarget＂ concept, has been proposed from China. The network target strategy is able to illustrate the complex interactions among the biological systems, drugs, and complex diseases from a network perspective, and thus provides an innovative approach to access ancient remedies in a precision manner and at a systematic level, which also highlights TCM＇s potential in current medical systems.

Therapeutic developments in metabolic dysfunction-associated fatty liver disease

Metabolic dysfunction-associated fatty liver disease(MAFLD)has become one of the most prevalent chronic liver diseases worldwide,bringing risk of multiorgan disfunctions including cardiovascular events,complications of cirrhosis,and even malignance.In terms of health burden management,screening patients with high risk of MAFLD and providing individual comprehensive treatment is critical.Although there are numerous agents entering clinical trials for MAFLD treatment every year,there is still no effective approved drug.The nomenclature of MAFLD highlighted the concomitant metabolic disorders and obesity.MAFLD patients with type 2 diabetes had higher risk of developing liver cirrhosis and cancer,and would benefit from anti-hyperglycemic agents;overweight and obese patients may benefit more from weight loss therapies;for patients with metabolic syndrome,individual comprehensive management is needed to reduce the risk of adverse outcomes.In this review,we introduced the current status and advances of the treatment of MAFLD based on weight loss,improving insulin resistance,and management of cardiometabolic disorders,in order to provide individualized therapy approaches for patients with MAFLD.