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.

Role of antidiabetic agents in type 2 diabetes patients with chronic kidney disease

Insulin resistance is a condition in which the target tissues have a decreased response to insulin signaling,resulting in glucose uptake defect,and an increased blood sugar level.Pancreatic beta cells thus enhance insulin production to compensate.This situation may cause further beta cell dysfunction and failure,which can lead diabetes mellitus(DM).Insulin resistance is thus an important cause of the development of type 2 DM.Insulin resistance has also been found to have a strong relationship with cardiovascular disease and is common in chronic kidney disease(CKD)patients.The mechanisms of insulin resistance in CKD are complex and multifactorial.They include physical inactivity,inflammation and oxidative stress,metabolic acidosis,vitamin D deficiency,adipose tissue dysfun-ction,uremic toxins,and renin-angiotensin-aldosterone system activation.Currently,available anti-diabetic agents,such as biguanides,sulfonylureas,thiazolidinediones,alfa-glucosidase inhibitors,glucagon-like peptide-1-based agents,and sodium-glucose co-transporter-2 inhibitors,have different effects on insulin resistance.In this short review,we describe the potential mechanisms of insulin resistance in CKD patients.We also review the interaction of currently available anti-diabetic medications with insulin resistance.

Systems pharmacology for traditional Chinese medicine with application to cardio-cerebrovascular diseases

Identified as a treasure of natural herbal products,traditional Chinese medicine(TCM)has attracted extensive attention for their moderate treatment effect and lower side effect.Cardio-cerebrovascular diseases(CCVD)are a leading cause of death.TCM is used in China to prevent and treat CCVD.However,the complexity of TCM poses challenges in understanding the mechanisms of herbs at a systems-level,thus hampering the modernization and globalization of TCM.A novel model,termed traditional Chinese medicine systems pharmacology(TCMSP)analysis platform,which relies on the theory of systems pharmacology and integrates absorption,distribution,metabolism,excretion and toxicity(ADME/T)evaluation,target prediction and network/pathway analysis,was proposed to address these problems.Here,we review the development of systems pharmacology,the TCMSP approach and its applications in the investigations of CCVD and compare it with other methods.TCMSP assists in uncovering the mechanisms of action of herbal formulas used in treating CCVD.It can also be applied in ascertaining the different syndrome patterns of coronary artery disease,decoding the multi-scale mechanisms of herbs,and in understanding the mechanisms of herbal synergism.

Novel wine in an old bottle:Preventive and therapeutic potentials of andrographolide in atherosclerotic cardiovascular diseases

Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets.Therefore,the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention.Andrographolide(AG)is a diterpenoid lactone compound extracted from Andrographis paniculata.In addition to its use in conditions such as sore throat,AG can be used to prevent and treat ASCVD.It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity,diabetes,hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis(AS)including lipid accumulation,inflammation,oxidative stress and cellular abnormalities by regulating various targets and pathways.However,the pharmacological mechanisms of AG underlying the prevention and treatment of ASCVD have not been corroborated,which may hinder its clinical development and application.Therefore,this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD.The findings support the use of the old pharmacological compound(‘old bottle’)as a novel drug(‘novel wine’)for the prevention and treatment of ASCVD.Additionally,this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG,aiming to provide more information regarding the clinical application and further research and development of AG.

Pharmacological effects of volatileoil from Alpinia officinaruim in treating cardiovascular diseases

Galangal(Alpinia officinaruim Hance)is the rhizome of the perennial herb belonging to Zingiberaceae family.There are many active components in galangal,such as volatile oil,flavonoids,terpenoids,phenylpropanoids and glycosides,among which the content of volatile oil is higher.The bioactivities of galangal volatile oil on health effect includesanti-inflammatory,anti-hypertension,anti-oxidation and prevention of cardiovascular diseases.Cardiovascular disease(CVD)is a kind of diseases related to circulatory system,which is also called circulatory system diseases.Over the past decade,the number of people dying from CVD has increased by 12.5%worldwide,and it is now the leading cause of human death worldwide.Studies have shown that galangal volatile oil has good pharmacological effects in treating CVD.①Regulation of glucose and lipid metabolism:studies have found that abnormal lipid metabolism can lead to obesity,diabetes,CVD and other diseases.The serum total triglyceride(TG)content in liver and serum will increase in patients with abnormal fat metabolism.The results showed that the volatile oil of galangal could increase the excretion of neutral cholesterol,significantly reduce liver TG and serum TG,and thus regulate glucose and lipid metabolism,prevent lipid deposition and prevent CVD.②Improving insulin resistance(IR):inhibition of inflammatory cytokines such as IL^(-1),IL-6 activation and expression of TNF-α,improves IR,thereby protecting myocardium from IR-mediated damage.Through the establishment of endothelial cell injury model induced by high glucose in vitro,it was found that the volatile oil of galangal can significantly reduce the secretion of pro-inflammatory cytokines TNF-αand IL-8,and inhibit the expression of ICAM-1 and VCAM-1 induced by high glucose,suggesting that it has protective effect on endothelial dysfunction and inflammation induced by high glucose.③Regulate blood oxygenation:during acute myocardial hypoxia,the activity of free radical scavenging system is decreased,and oxygen free radicals are produced in large quantity,which reacts with unsaturated fatty acids on the cell membrane and forms lipid peroxidation,resulting in myocardial structural damage.The results showed that the water extract of Galangal could reduce the content of MDA in blood and protect the SOD activity of ischemic and hypoxic myocardium.④Protective effect of vascular endothelial cells(ES):ES injury is the pathological basis of some cardiovascular diseases.The results showed that the volatile oil of galangal had a protective effect on ES apoptosis.Compared with the morphology and activity of ES treated with oxidized LDL,galangal volatile oil could ameliorate these morphological changes and improve cell viability.⑤Antiplatelet agglutination:inhibit platelet aggregation and thromboxane release,improve blood circulation,and have obvious anti-thrombotic effect,which has a good effect on the treatment and prevention of cardiovascular diseases.The results showed that the volatile oil of galangal had inhibitory effect on platelet aggregation and anticoagulant effect.In conclusion,the volatile oil of galangal can be used to prevent and treat cardiovascular diseases.Based on the mechanism of CVD,this study summarized the role of the essential oil of Alpinia officinaruim in CVD,providing basis for the clinical application of alpiniaofficinalis essential oil in the prevention and treatment of CVD and the development of new drugs.

The therapeutic mechanism of black soybean in atherosclerosis based on network pharmacology

Objective:To investigate the cardiovascular mechanism of black soybean,the biological characteristics of black soybean were studied by bioinformatics,and the mechanism of its treatment for atherosclerosis was further determined.Methods:Firstly,the basic data sets of effective components and corresponding targets of black beans were constructed,and then mapped to the AS background network obtained from DisGeNET database and CTD database.Finally,the potential targets of black beans acting on AS were obtained.After constructing the protein-protein interaction(PPI)network,the topological characteristics of these targets were analyzed.KEGG and GO were enriched to obtain the potential mechanism of black soybean acting on AS.Results:There were 12 bioactive components reported in black soybean.Among them,beta-sitosterol,stigmasterol and N-(4-hydroxyphenylethyl)ACTINIDINE were the three most active components.There are 19 targets of black soybeans acting on PPI network of AS disease.Among them,ADRB2 and PTGS2 are important targets for black soybeans to alleviate AS.The therapeutic pathways include arachidonic acid metabolism and serotonin synapse.Conclusion:Black soybean can play a therapeutic role in AS through multi-target and multi-pathway.The application of network pharmacology can quickly clarify the characteristics of functional foods and identify their potential targets and mechanisms for disease treatment.

Pharmacological Effects and Molecular Mechanism of Osthole

Osthole has various pharmacological effects such as anti-cancer,anti-inflammation,prevention and treatment of cardiovascular diseases and neuroprotection.This paper reviews the advances in the research of the pharmacological effects and molecular mechanisms of osthole,in order to provide new ideas for further research and clinical application of osthole.

苦参碱对心血管系统疾病药理作用及机制的研究进展

目的:对苦参碱的药理作用及机制进行综述,为进一步研究苦参碱对心血管作用奠定基础。方法:对国内外相关文献进行梳理总结,分类阐述苦参碱对心血管的药理作用及相关机制。结果:苦参碱具有抗心律失常、抗心肌损伤、抑制心肌细胞肥大、抗心肌细胞纤维化、抗柯萨奇病毒、改善心衰等心血管作用,其治疗心血管疾病的优势日益凸显。结论:通过对苦参碱治疗心血管疾病药理作用及机制研究的讨论,以期为今后以苦参碱为基础的新药开发和临床应用提供参考。

A Non-Invasive Skin Treatment Combining LED with Pharmacologic and Ultrasonic Technologies for Facial Rejuvenation

Background: Non-invasive facial treatments have the ability to rejuvenate the facial profile when specific pharmacologic agents and modalities are prescribed and used in combination taking into consideration each patient’s unique skin type and condition. RATIONALE Epinova is a non-invasive skin treatment that combines the correct concentrations and combinations of topicals and modalities to elicit facial rejuvenation with no down-time or side effects. Purpose: This paper focuses on facial rejuvenation improvements combining the RATIONALE Essential Six skincare system (RATIONALE, Victoria, Australia) to protect and repair the skin with the RATIONALE Epinova facial treatment every 4-6 weeks—which uses non-invasive technologies and professional strength active ingredients to deliver visible changes to skin tone and texture. Methods: Subjects underwent a RATIONALE consultation, including taking a skin history and skin imaging, followed by a data analysis and diagnosis of skin condition and prescription of a customized RATIONALE treatement (Epinova), including appropriate pharmacologic agents and treatment with personalized photo/sono therapeutic devices. Results: Subjects reported increased skin hydration, tactile improvements, skin firmness and visible radiance following the RATIONALE Epinova treatment. Further investigations will be initiated to explore the potential for longer term improvements, including connenctive tissue deposition, reduction of erythema etc. Treatments should be performed every 4-6 weeks for patients under 40 and every 3-4 weeks for patients over 40, to support cell differentiation, migration and desquamation to achieve non-invasive facial rejuvenation. Conclusion: This study demonstrated that the synergy of pharmacologic, LED light therapy and ultrasonic technologies when prescribed and administered by a trained skin therapist, can lead to a visible improvement in the signs of facial ageing and photodamage, restoring the appearance of healthy, radiant skin. .

桂枝及桂枝类方治疗心血管疾病研究进展

桂枝是我国传统中药材,因其具有发汗解肌、平冲降逆、温经通脉、温阳助气等功效被广泛应用于医疗实践中,特别是在心血管疾病中尤为突出。现代研究发现桂枝及桂枝类方具有保护血管和调节血管活性因子、抗炎、抗氧化应激、改善冠状动脉循环和心肌纤维化、降血压、防治心力衰竭等作用,充分发挥对心血管疾病的防治作用。文章综述了桂枝及桂枝类方从抗冠心病、抗高血压、改善冠状动脉循环和心肌纤维化、调节血脂代谢、改善心肌缺血再灌注、防治心力衰竭等内容,以求为桂枝及桂枝类方在心血管疾病的应用和研究提供参考和依据。

丹参及其有效成分对心血管系统的药理机制研究进展

中国传统药材丹参因极佳的活血祛瘀、通经止痛、清心除烦等功效历来被广泛用于医疗实践中,尤以在心血管系统中的应用突出。现代研究发现,丹参及其活性成分具有抗凝、降脂、抗血栓形成、抗炎抗氧化应激、降压、保护心肌细胞、减少心肌细胞凋亡率、保护血管和促进血管扩张、改善线粒体功能障碍和微循环、防治心室肥大等作用,使得其对心血管系统疾病有着良好的防治效果。综述丹参及其有效活性成分从抗动脉粥样硬化、保护心肌细胞、保护血管、改善心肌缺血和缺血再灌注损伤、防治高血压和心室肥大等内容,力求为丹参在心血管系统疾病的应用和研究提供参考。

四逆散药理作用及治疗内科疾病的临床应用研究

四逆散为《伤寒论》中记载的经典名方,至今约有1800年的历史,适用于少阴病症,临床多以手足不温、泄利下重、腹痛、脉弦等为辨证要点,具有透邪解郁、疏肝理脾之功效。中医认为该方剂治疗病症与阳衰阴盛有本质的区别,该证属外邪传经入里,气机为之郁遏,失于疏泄,阳气内郁不能达于四末所致,为阴中涵阳、惟气不宣通而致四肢逆冷。四逆散的应用十分广泛,几乎各系统疾病均可以该方剂为基础方进行辨证施治,尤其是现临床对四逆散的研究更加深入,其药理作用和应用领域也进一步被拓展,可广泛用于治疗胃肠肝胆疾病、精神类疾病、肿瘤疾病等。文章通过分析近年来四逆散的应用文献,总结其药理和治疗作用,为临床对四逆散有更加深入地了解,推动该方剂在临床的进一步开发应用。

植物药总黄酮的药理作用机制及应用进展

植物药总黄酮(total flavones,TF)包含的类型十分复杂,每种植物药所包含的总黄酮各不相同。植物药总黄酮具有多种药理学作用,包括对心血管系统的作用,能够保护缺血性心肌损伤(ischemic myocardial injury,ICM)以及抗高血压(hypertension,HBP)。还能够保护肝脏和肾脏,对抗肝纤维化(hepatic fibrosis,HF),保护肾功能,另外对癌症和肿瘤也有一定的对抗作用。除此之外植物药总黄酮还具有调节代谢的药理学作用。凭借丰富的药理学作用,总黄酮逐渐受到现代药理学人员的重视,是中药方剂的重要成分,能够治疗高血压病以及病毒性感染所致的心肌损伤,也能够治疗药物性肝损伤(drug-induced liver injury,DILI)、终末期肝病(end stage liver disease,ESLD)及其并发症以及失代偿期乙型肝炎肝硬化(decompensated hepatitis B cirrhosis)等肝脏疾病。在癌症的对抗中,能够抗肝癌(liver cancer)、甲状腺癌(thyroid cancer,THCA)以及妇女晚期卵巢癌(advanced ovarian cancer)等多种癌症。在呼吸系统中能够治疗颈淋巴结炎(cervical lymphadenitis)、上呼吸道感染(upper respiratory tract infection,URTI)、急性扁桃体炎(acute tonsillitis)等。还能够治疗白癜风(vitiligo)和黄体功能不全型先兆流产患者等。总结植物药总黄酮药理作用机制及其临床应用情况,以期能够为后续研究和实践提供理论和信息基础。

Notch信号通路——对健康和疾病的机械论观点

The Notch signaling pathway is evolutionarily conserved across metazoan species and plays key roles in many physiological processes.The Notch receptor is activated by two families of canonical ligands(Deltalike and Serrate/Jagged)where both ligands and receptors are single-pass transmembrane proteins usually with large extracellular domains,relative to their intracellular portions.Upon interaction of the core binding regions,presented on opposing cell surfaces,formation of the receptor/ligand complex initiates force-mediated proteolysis,ultimately releasing the transcriptionally-active Notch intracellular domain.This review focuses on structural features of the extracellular receptor/ligand complex,the role of posttranslational modifications in tuning this complex,the contribution of the cell membrane to ligand function,and insights from acquired and genetic diseases.

天麻钩藤饮在防治心脑血管疾病中的应用研究评述

天麻钩藤饮是平肝息风、清热活血、补益肝肾的代表方,其主要化学成分为黄酮类、生物碱类、酚酸类化合物,精制工艺技术包含超滤膜技术、大孔树脂法、吸附澄清法、醇沉法。天麻钩藤饮药理活性广泛,具有降低血压、神经功能保护、镇痛镇静、抗炎作用,在临床上常单独或联合给药用于心脑血管疾病的治疗,特别是在高血压、头痛、脑卒中、眩晕、创伤性脑损伤、高脂血症、老年性耳鸣等方面治疗效果颇为显著。本文对近年来有关天麻钩藤饮的化学成分、精制工艺、主要药理作用和临床实践的研究报道进行整理综述,以期为天麻钩藤饮后续研究和相关药物的开发提供参考。

追风七化学成分及药理作用研究进展

追风七药用价值高,资源分布广,常用于治疗头痛-头晕、小儿惊风、高血压、腰腿疼痛、月经不调等疾病,在临床研究中具有潜在的开发前景。现代研究表明,追风七主要化学成分为鞣质类、三萜类、黄酮类、苯丙素类等,具有良好的保护心血管、保肝、抗病毒、抗菌、抗肿瘤、抗炎等多种药理作用。通过对追风七的化学成分和药理作用的研究进展进行综述,以期为追风七今后的研究开发提供参考依据。

基于网络药理学和分子对接的补气通络颗粒抗心血管疾病作用机理研究

目的筛选补气通络颗粒抗心血管疾病(CVD)的药效成分及作用机制。方法采用网络药理学方法对补气通络颗粒的化学成分进行ADME活性筛选、靶点预测、网络构建、蛋白互作(PPI)分析、京都基因与基因组百科全书(KEGG)和基因本体(GO)分析,利用分子对接(Sybyl-X软件)技术验证筛选出潜在活性成分和关键靶点。结果补气通络颗粒中已鉴定的72个化合物中15个具有良好的ADME性质,这些潜在的活性成分中,共10个成分及其对应的26个靶标与补气通络颗粒抗CVD的活性密切相关。通过构建“活性成分-靶点”网络及对网络进行分析,共获得4个关键化合物和3个关键靶标。此外,在对靶点进行KEGG通路分析时,共获得7条与抗CVD相关的通路。GO富集分析结果显示,改善血液循环是补气通络颗粒抗CVD的主要作用机制之一。分子对接实验表明筛选的关键靶蛋白和对应的活性成分对接良好。结论补气通络颗粒可通过多成分、多靶点及多通路的机制发挥其抗CVD活性。

银杏叶对心脑血管疾病药理作用的研究进展

银杏叶,性平,味甘、苦、涩,归心经,具有化浊降脂、活血化瘀的功效。其抗心脑血管疾病的有效成分为银杏内酯、银杏多糖、银杏黄酮等,主要通过扩张血管、促进血液循环、保护心脑血管的药理作用来抗心脑血管疾病,临床上运用银杏叶防治高血压、动脉粥样硬化、缺血性的脑损伤等心脑血管疾病。现从物质基础、药理作用、临床应用等方面对于银杏叶防治心脑血管疾病药理作用的研究进展进行了系统性的阐述,旨在为银杏叶及其化学成分抗心脑血管疾病作用的深入研究提供参考依据。

降压治疗对白大衣高血压病人预后影响的Meta分析

目的:通过Meta分析探讨降压治疗对白大衣高血压(WCH)病人预后的影响。方法:计算机检索PubMed、EMbase、the Cochrane Library和Web of Science数据库中降压治疗对WCH病人预后影响的相关文献。由2名研究员独立对纳入文献进行质量评价并提取文献资料,采用RevMan5.3软件进行Meta分析。结果:纳入8篇文献,涉及2 886例受试者,包括914例服用降压药物的WCH病人和1 972例未经治疗的WCH病人,随访时间为1.0~10.9年。Meta分析显示,接受降压药物治疗的WCH病人心血管事件发生率高于未经治疗的WCH病人[RR=1.67,95%CI(1.35,2.06),P<0.000 01];在进行亚组分析时,年龄≤60岁的WCH病人中,接受降压治疗的心血管事件发生率低于未经治疗,但差异无统计学意义[RR=0.90,95%CI(0.51,1.59),P=0.72]。结论:现有证据表明,接受过降压治疗的WCH病人心血管事件风险未降低。由于纳入研究较少和降压治疗不明确等局限性,仍需要大量随机对照试验确认降压治疗对WCH病人是否有效。

维持性血液透析患者不同初始剂量静脉铁剂治疗前后炎症、氧化应激的变化及对主要不良心血管事件的影响

目的探讨维持性血液透析(MHD)患者应用不同初始剂量静脉铁剂治疗前后炎症、氧化应激的变化及对主要不良心血管事件(MACE)的预测价值。方法回顾性分析2017年8月至2019年8月在秦皇岛市第一医院血液透析室行MHD治疗的158例患者的临床资料,根据初始静脉铁剂用量的不同分成高剂量组(每月400 mg蔗糖铁,78例)和低剂量组(每月200 mg蔗糖铁,80例)。两组用药2.5个月后所有患者均1次/2周静脉滴注100 mg蔗糖铁,维持此方案24个月以上。比较两组治疗前、治疗12个月及24个月血红蛋白(Hb)、血清铁蛋白(SF)、转铁蛋白饱和度(TSAT)、炎症因子[C-反应蛋白(CRP)、白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)]及氧化应激因子[超氧化物歧化酶(SOD)、丙二醛(MDA)、髓过氧化物酶(MPO)]指标,观察两组3年内MACE发生情况,并通过ROC分析有关指标对MACE发生的预测价值。结果治疗12个月及24个月两组Hb、SF、TSAT水平及血清CRP、IL-6、TNF-α、MDA、MPO水平均较治疗前增高差异有统计学意义(P<0.05),血清SOD水平均较治疗前降低差异有统计学意义(P<0.05)。治疗24个月,两组Hb、SF、TSAT水平及血清CRP、IL-6、TNF-α、MDA、MPO水平均较治疗12个月增高,血清SOD水平均较治疗12个月降低,差异有统计学意义(P<0.05)。高剂量组MACE发生率与低剂量组比较差异无统计学意义(χ^(2)=0.396,P>0.05)。MACE组血清IL-6、MDA水平高于非MACE组,差异有统计学意义(t=5.352、8.584,P<0.05)。MACE组血清SOD水平低于非MACE组,差异有统计学意义(t=2.467,P<0.05)。血清IL-6、SOD、MDA水平预测MHD患者发生MACE的ROC曲线下面积分别为0.741、0.691、0.887,敏感度分别为57.80%、64.40%、84.40%,特异度分别为81.40%、69.00%、79.60%。结论静脉铁剂200 mg/月和400 mg/月两种给药方法均可有效纠正MHD患者铁缺乏,均加重患者炎症及氧化应激状况;血清IL-6、SOD、MDA水平可预测MHD患者MACE的发生。