Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

Pharmacological effects of bioactive agents in earthworm extract:A comprehensive review

This review compiles information from the literature on the chemical composition,pharmacological effects,and molecular mechanisms of earthworm extract(EE)and suggests possibilities for clinical translation of EE.We also consider future trends and concerns in this domain.We summarize the bioactive components of EE,including G-90,lysenin,lumbrokinase,antimicrobial peptides,earthworm serine protease(ESP),and polyphenols,and detail the antitumor,antithrombotic,antiviral,antibacterial,anti-i nflammatory,analgesic,antioxidant,wound-healing,antifibrotic,and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies.We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies,and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance.The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis.Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix.The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage.Earthworms have evolved a well-developed defense mechanism to fight against microbial infections,and the bioactive agents in EE have shown good antibacterial,fungal,and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections,effectively reducing pain.Recent studies have also highlighted the role of EE in lowering blood glucose.EE shows high medicinal value and is expected to be a source of many bioactive compounds.

Gentiana macrophylla Pall.:a review of the basic source,traditional use,chemical components,pharmacological activities and quality control

Gentiana macrophylla Pall.(G.macrophylla),whose genus and family belong to the Gentianaceae and Gentiana.The main distribution centers of G.macrophylla resources were the Loess Plateau and the eastern Qinghai-Tibet Plateau in China.G.macrophylla,as a traditional medicine,has a long history and was used in different ethnic medicines.Its roots were used in traditional Chinese medicine,which had the effect of anti-inflammatory,anti-rheumatism,antiviral,promote blood circulation,eliminate swelling and pain,while its flowers were used in traditional Mongolian medicine,which had the effect of removing“Xieriwusu”(“Xieriwusu”means rheumatism),antiviral,reducing swelling.From previous studies,it could be found that there were more than forty components isolated and identified from G.macrophylla.The main chemical components were iridoids,flavonoids,triterpenoids,steroids,phenylpropanoids,and alkaloids.Iridoid terpenoid components represented by gentiopicroside and Loganic acid were the main components of the root of G.macrophylla,which had anti-inflammatory,antioxidant,hepatoprotective,analgesic,antibacterial and promote gastrointestinal tract activities.The flower mainly contains isoorientin and isovitexin as the representative of flavonoids.They have anti-tumor,liver protection,heart protection,inhibition of acetylcholinesterase and inhibition of melanin.It could be seen from previous studies that the research on G.macrophylla was mainly focused on the root,and the flower was rarely studied.It was reported that the experimental data of the anti-inflammatory and anti-tumor effects of G.macrophylla flowers show that its curative effect was very good.Therefore,the flowers of the flower of G.macrophylla can be used as potential medicinal parts for research.Given that flavonoids are mostly found in flowers and exhibit a range of functions,it is possible to investigate the flowers in order to learn more about G.macrophylla’s potential medical benefits.Based on botanical books,Chinese classic texts,medical monographs and academic search engines(Google,Google Scholar,Web of Science,SciFinder,Pubmed,CNKI,Sci-hub,Elsevier and Wanfang),the data and information on G.macrophylla in the past 20 years are inquired and summarized comprehensively.The basic source,traditional use,chemical composition,biological activity,pharmacodynamics and quality control of G.macrophylla was systematically reviewed,in order to provide reliable basis for the subsequent development and utilization of G.macrophylla.

Pharmacological effects of volatile oil from chrysanthemum and its associated mechanisms:a review

Volatile oil(VO)is the main chemical component of common plants in Chrysanthemum genus,and it possesses several beneficial pharmacological properties,including bacteriostatic,antioxidant,anti-tumor,anti-inflammatory,antipyretic,analgesic,antiosteoporotic,antihypertensive,sedative,and hypnotic effects.To date,research on the effective components of Chrysanthemum extract has mainly focused on flavonoids,whereas limited data are available on the chemical constituents and underlying mechanisms of action of the VO components.In this review,the pharmacological activities and mechanisms of VO are comprehensively reviewed with the aim of providing a foundation for further development for medicinal,aromatherapy,and diet therapy applications.

Boswellic acids: a review on its pharmacological properties, molecular mechanism and bioavailability

Boswellic acids is a general term for a series of pentacyclic triterpenoid compounds that are isolated from the oleogin resin of the Boswellia genus and serve as the main active ingredient.It exhibits a wide range of biological activities,such as anti-inflammatory,anti-cancer,antibacterial,antiviral,hepatoprotective,neuroprotective,anti-diabetic,and anti-thrombotic properties.As a result,it has gained significant recognition among practitioners of traditional Chinese and Indian medicine.These biological effects may be associated with multiple molecular targets and signal transduction pathways.However,the poor pharmacokinetic properties of the substance lead to lower bioavailability,which affects its effectiveness.To address this issue,scientists have proposed a number of strategies,such as solid dispersions,phytosome®technologies,and novel drug delivery systems.This article aims to provide a comprehensive overview for boswellic acids on the phytochemistry,molecular mechanisms,potential therapeutic applications,and strategies to improve bioavailability.

Research Progress on Purification Process, Content Determination and Pharmacological Action of Atractylodin

Atractylodis Rhizoma comes from the dry rhizome of Atractylis lancea or Atractylodes chinensis in the Compositae family,and it is suitable for preventing and treating diseases such as cold,edema,night blindness and rheumatic arthralgia.Atractylodin is the main active component extracted and isolated from Atractylodis Rhizoma.A large number of studies have found that atractylodin has excellent drug activity in improving gastrointestinal emptying,anti-inflammation,inhibiting malignant tumor and reducing blood lipid.In this paper,the purification process and pharmacological activity of Atractylodin were summarized to provide a theoretical basis for basic research,clinical application and further development and utilization of atractylodin.

Pharmacological Treatment for Atrial Fibrillation—Modalities in Equines and Companion Animals

Cardiac arrhythmias are probably more common in horses than in any other domestic animal species where poor performance and exercise intolerance is the most frequent clinical complaint. Atrial fibrillation is a type of cardiac arrhythmia that appears as a common finding during medical examinations in humans, large breed dogs and horses. Clinical presentations are of a particular value in racehorses in high performing activities. Atrial fibrillation is characterized by an irregular heart rhythm, secondary to a primary disease or without any sign of comorbidity. The generation and maintenance of Atrial Fibrillation requires a substrate. Some breeds have a genetic predisposition to developing Atrial Fibrillation. Most cases of Atrial Fibrillation are of the paroxysmal type and self-regulate within a few hours to days without the need for treatment. The focus of this study is on the arrhythmic agents that are used for the treatment of Atrial Fibrillation, therefore other arrhythmic agents may not be included, or are included to demonstrate their effect on increasing, inhibiting or decreasing efficacy when used together with medications for the treatment of Atrial Fibrillation. The “working horse” for the pharmacological treatment of Atrial Fibrillation is Quinidine.

Research on Purification Processand PharmacologicalAction of Andrographolide

This paper reviews the purification process,content determination methods and pharmacological action of Andrographolide,aiming to provide new ideas for the subsequent study of Andrographolide and its related drug development and application.

Chemical constituents and pharmacological effects of Lonicerae japonicae

Lonicera japonica,also known as honeysuckle,is an evergreen shrub in the family of Syzygium.By consulting Sciencedirect databases and Web of Science databases,79 related articles were found,of which 22 were related to chemical composition and pharmacological activity.These articles show that L.japonica has a wide range of pharmacological activities,including antiviral,anti-tumor,and antioxidant effects.These activities have important applications in the pharmaceutical,food,and fragrance industries.This review focuses on the chemical composition and pharmacological effects of L.japonicae,which is of great significance to the development of new drugs and therapeutic methods.

Chemical constituents and pharmacological effects of Croton crassifolius

Croton crassifolius(CC)is a kind of traditional Chinese medicine rich in terpenoids,with among which diterpene species are the most.CC had biological activities in the treatment of cancer,inflammation,ulcerative colitis,osteoporosis and Alzheimer’s disease.This study reviews the chemical compositions and pharmacological activities of CC to provide reference for further research.

Chemical composition and pharmacological activities of Atractylodes lancea:A review

Atractylodes lancea(called Cangzhu in China)is a medicinal plant that has long been used as tonic agent in various ethno-medical systems in East Asia,especially in China,for the treatment of gastrointestinal dysfunction,cancer,osteoporosis,obesity and fetal irritability.We used the TCMSP database to search for the main active ingredients and traditional Chinese medicine targets of Atractylodes macrocephala.There are a total of 38 related articles,of which 27 are closely related to chemical composition and activity.This study reviews the chemical components and pharmacological effects of A.lancea,aiming to provide reference for its further research and development.

Chemical composition and pharmacological activities of the Phellodendron chinense Schneid

Phellodendron chinense Schneid(P.chinense),as a traditional Chinese medicine,is commonly used in clinical practice.It has the effects of drying dampness,clearing heat,detoxifying,purging fire,and reducing swelling.Its main chemical components are flavonoids and alkaloids,which have various pharmacological effects such as lowering blood sugar,lowering blood pressure and immunosuppression.With the continuous development of modern science and technology,the research on P.chinense Schneid has increased.This study reviews the chemical components and pharmacological effects of P.chinense Schneid,and provides reference for its further research and development.

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.

Advances in Pharmacological Effects of Stevioside

Stevioside is a low-calorie high-power sweetener with a variety of positive pharmacological effects.With the growing attention to health,stevia leaf has garnered widespread interest at home and abroad.This article reviews the main pharmacological effects of stevioside and their mechanisms,in order to provide references for the research on the edible and medicinal value of stevioside.

The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification

Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii.Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.Results Six potential active components,namely quercetin,β-sitosterol,stigmasterol,7-Omethylluteolin-6-C-beta-glucoside_qt,atropine,and glycitein,were identified to have potency in improving exercise fatigue via multiple pathways,such as the PI3K-Akt,neuroactive ligand-receptor interaction,IL-17,TNF,and MAPK signaling pathways.The immunofluorescence results indicated that quercetin,a significant active component in Fructus lycii,increased the mean staining area of 2-NBDG,TMRM,and MitoTracker,and decreased the area of CellRox compared to the control.Furthermore,the protein expression levels of p-38 MAPK,p-MAPK,p-JNK,p-PI3K,and p-AKT markedly increased after quercetin treatment.Conclusion Fructus lycii might alleviate exercise fatigue through multiple components and pathways.Among these,quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress.The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Qizhu prescription for treating breast cancer

Objective:To investigate the mechanism underlying the effects exerted by the Qizhu prescription(QZP)in breast cancer(BC),and the respective targets.Methods: Expression data from the ArrayExpress and The Cancer Genome Atlas(TCGA)were used to identify differentially expressed genes(DEGs)in BC.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the DEGs to identify genes involved in protein–protein interactions.Molecular docking was used to explore the dynamic relationship between active molecules and targets.Cell function experiments and animal studies were conducted to evaluate the effects of hub genes and active QZP compounds on BC cell behavior.Results: Among the 25 evaluated BC-related targets of QZP,matrix metalloproteinase-1(MMP1)and epidermal growth factor receptor(EGFR)exhibited the highest degrees of dysregulation.GO and KEGG enrichment analyses revealed that the anti-BC targets of QZP primarily affected drug responses and pathways in cancer cells.Molecular docking analysis suggested potential interactions between EGFR and quercetin/luteolin,as well as between MMP1 and luteolin/kaempferol/quercetin.Quercetin significantly reduced BC cell proliferation,migration,invasion,and tumor development in vivo.Treatment of BC cells with quercetin decreased the expression or activation of several associated proteins.Conclusion: The findings of our study provide new insights into the therapeutic potential of traditional Chinese medicine against BC,with particular reference to QZP.

Potential pharmacological mechanisms of digallate in the treatment of enteritis based on network pharmacology and molecular docking

Background:In order to investigate the possible pharmacological mechanism of digallate in Galla Chinensis for treating enteritis,providing reference for the search and exploration of effective drugs for treating enteritis.Method:Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PharmMapper,DisGeNET,DrugBank,and GeneCards databases were used to obtain drug and disease-related target information.Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were performed,and the main therapeutic pathways and targets were identified by combining protein-protein interaction networks and cytoHubba plug-in.Molecular docking was used to validate the results.Result:297 drug related targets,2436 disease related targets,and 66 target points related to digallate were predicted to be associated with enteritis.10 related signal pathways and 10 key genes were identified.Conclusion:Digallate may be utilized to treat enteritis by acting on similar pathways,such those related to pathways in cancer,lipid and atherosclerosis,proteoglycans in cancer,Rap1 signaling pathway,PI3K-Akt signaling pathway and other targets such as IGF1,EGFR,SRC,IGF1R,PPARG.

Research progress on chemical constituents and pharmacological activities of Amomum longiligulare T.L.Wu

In order to develop and utilize the tropical medicinal resource Amomum(A.)longiligulare T.L.Wu more reasonably and effectively,this paper summarizes the research progress in chemical constituents and pharmacological activities of A.longiligulare by consulting the literatures,so as to provide a certain theoretical basis for exploring its material basis.The chemical constituents of A.longiligulare mainly include volatile oil,diphenylheptane and flavonoids,which have good efficacy in anti-peptic ulcer,as well as antioxidant,analgesic and other pharmacological activities.This paper briefly discusses the reasons for the differences in the composition of volatile oil studied by different scholars.By summarizing its pharmacological activities,it is found that its various pharmacological activities may be the basis of its anti-peptic ulcer.

Quinones from Cordia species from 1972 to 2023:isolation,structural diversity and pharmacological activities

Plants of the genus Cordia(Boraginaceae family)are widely distributed in the tropical regions of America,Africa,and Asia.They are extensively used in folk medicine due to their rich medicinal properties.This review presents a comprehensive analysis of the isolation,structure,biogenesis,and biological properties of quinones from Cordia species reported from 1972 to 2023.Meroterpenoids were identified as the major quinones in most Cordia species and are reported as a chemotaxonomic markers of the Cordia.In addition to this property,quinones are reported to display a wider and broader spectrum of activities,are efficient scaffold in biological activity,compared to other classes of compounds reported in Cordia,hence our focus on the study of quinones reported from Cordia species.About 70 types of quinones have been isolated,while others have been identified by phytochemical screening or gas chromatography.Although the biosynthesis of quinones from Cordia species is not yet fully understood,previous reports suggest that they may be derived from geranyl pyrophosphate and an aromatic precursor unit,followed by oxidative cyclization of the allylic methyl group.Studies have demonstrated that quinones from this genus exhibit antifungal,larvicidal,antileishmanial,anti-inflammatory,antibiofilm,antimycobacterial,antioxidant,antimalarial,neuroinhibitory,and hemolytic activities.In addition,they have been shown to exhibit remarkable cytotoxic effects against several cancer cell lines which is likely related to their ability to inhibit electron transport as well as oxidative phosphorylation,and generate reactive oxygen species(ROS).Their biological activities indicate potential utility in the development of new drugs,especially as active components in drug-carrier systems,against a broad spectrum of pathogens and ailments.

Cellular senescence throws new insights into patient classification and pharmacological interventions for clinical management of hepatocellular carcinoma

BACKGROUND Cellular senescence,a state of stable growth arrest,is intertwined with human cancers.However,characterization of cellular senescence-associated phenotypes in hepatocellular carcinoma(HCC)remains unexplored.AIM To address this issue,we delineated cellular senescence landscape across HCC.METHODS We enrolled two HCC datasets,TCGA-LIHC and International Cancer Genome Consortium(ICGC).Unsupervised clustering was executed to probe tumor heterogeneity based upon cellular senescence genes.Least absolute shrinkage and selection operator algorithm were utilized to define a cellular senescence-relevant scoring system.TRNP1 expression was measured in HCCs and normal tissues through immunohistochemistry,immunoblotting and quantitative real-time polymerase chain reaction.The influence of TMF-regulated nuclear protein(TRNP)1 on HCC senescence and growth was proven via a series of experiments.RESULTS TCGA-LIHC patients were classified as three cellular senescence subtypes,named C1–3.The robustness and reproducibility of these subtypes were proven in the ICGC cohort.C2 had the worst overall survival,C1 the next,and C3 the best.C2 presented the highest levels of immune checkpoints,abundance of immune cells,and immunogenetic indicators.Thus,C2 might possibly respond to immunotherapy.C2 had the lowest somatic mutation rate,while C1 presented the highest copy number variations.A cellular senescence-relevant gene signature was generated,which can predict patient survival,and chemo-or immunotherapeutic response.Experimentally,it was proven that TRNP1 presented the remarkable upregulation in HCCs.TRNP1 knockdown induced apoptosis and senescence of HCC cells and attenuated tumor growth.CONCLUSION These findings provide a systematic framework for assessing cellular senescence in HCC,which decode the tumor heterogeneity and tailor the pharmacological interventions to improve clinical management.