迷迭香酸烷基酯的来源及药理活性研究进展

迷迭香酸是一种广泛存在于唇形科植物中的天然水溶性酚酸化合物,由咖啡酸和3,4-二羟基苯基乳酸酯化缩合而成,其具有抗氧化、抗菌、抗炎、抗肿瘤等广泛的药理活性。迷迭香酸衍生物主要是通过对迷迭香酸侧链羧基进行结构改造所得到的一系列化合物,其中具有不同长度烷基链的迷迭香烷基酯,研究最为广泛。迷迭香酸烷基酯体外药理活性研究显示,其具有抗心血管疾病、抗氧化、抗菌、抗炎、抗过敏等药理活性,而且随着酯链长度的不同其活性强度及作用机理存在一定差异。本文主要对迷迭香酸烷基酯的来源及其药理活性进行综述,为迷迭香酸及迷迭香酸烷基酯在临床上的进一步开发利用提供理论依据。     

迷迭香酸对辐射损伤小鼠造血功能的保护作用

迷迭香酸是一种天然的水溶性多酚类化合物,最新研究发现具有抗紫外线辐射及细胞保护之效,实验中口服给予辐射损伤的ICR种小鼠不同剂量迷迭香酸(50、100、150、200 mg/kg),通过脏器系数、骨髓DNA含量、股骨有核细胞数(BMNC)、脾结节数(CFU-S)等指标检测其对小鼠造血系统的作用,并以外周血(WBC、HGB、PLT)及体重等指标,从整体水平上衡量迷迭香酸对小鼠造血功能的影响.研究发现不同剂量迷迭香酸对小鼠造血系统均有一定的保护作用,但呈倒“U”形剂量反应曲线,100 mg/kg作用尤为突出,各指标与单纯照射组相比均有显著性差异.     

新疆紫草中抗生育化学成分

从新疆紫草(Arnebia euchroma(Royle)Johnst.)的根部分得四种酚类化合物,经波谱分析,确定为rabdosiin二钾盐(dipotassium rabdosiin 1),迷迭香酸钾盐(potassium rosmarinate 2),迷迭香酸钠盐(sodium rosmarinate 3),阿魏酸钠盐(sodium ferulate 4).其中rabdosiin二钾盐具有显著的抗生育活性,而迷迭香酸钾盐、迷迭香酸钠盐和阿魏酸钠盐为首次从该植物中分离获得.     

大黄酸和迷迭香酸单用及配伍对慢性肾脏疾病的保护作用研究

目的:探讨大黄酸和迷迭香酸单用及配伍通过抗凋亡对5/6肾切除(5/6Nx)大鼠的保护作用。方法:采用5/6肾切除手术制作慢性肾损伤模型,将30只雄性SD大鼠随机分为假手术组、模型组、大黄酸(150 mg/kg/day)治疗组、大黄酸(75mg/kg/day)+迷迭香酸(75 mg/kg/day)治疗组和迷迭香酸(150 mg/kg/day)治疗组。给药1个月后处死大鼠,测量各组大鼠血清肌酐(Scr)和尿素氮(BUN)水平,通过HE染色观察肾组织形态学变化,通过TUNEL染色和测量肾组织中Bax、Bcl-2和cleaved caspase 3的表达检测细胞凋亡。结果:与模型组相比,大黄酸和迷迭香酸单用及配伍都可显著降低血清肌酐和尿素氮(P0.05)水平,改变组织形态学的变化和抑制肾脏细胞凋亡,且配伍的效果优于单用。结论:大黄酸和迷迭香酸配伍发挥肾保护作用明显优于单用,其作用机制与抗凋亡作用相关。     

迷迭香酸对羟自由基所致小鼠肝线粒体损伤的保护作用

探索迷迭香酸对羟自由基致小鼠肝脏线粒体氧化损伤的保护作用。采用羟自由基(.OH),诱导小鼠肝线粒体损伤后,通过测定线粒体肿胀度、膜流动性、丙二醛(MDA)含量及琥珀酸脱氢酶(SDH)活性等指标以确定迷迭香酸对小鼠肝线粒体羟自由基损伤的保护作用。结果迷迭香酸剂量依赖地抑制线粒体肿胀,提高膜流动性,降低MDA的生成,增强SDH活性,差异显著。本实验证明迷迭香酸可以抑制.OH所致的线粒体损伤。     

几种天然有机多酚酸体外抗脂质过氧化研究

通过天然有机多酚酸对H2O2诱导小鼠肝匀浆脂质过氧化和自发脂质过氧化的保护作用的体外实验,比较研究绿原酸、咖啡酸、迷迭香酸、阿魏酸、丹参素、原儿茶醛和3-羟基肉桂酸体外抗氧化能力的强弱,探讨其抗氧化能力产生机理及构效关系。结果表明,7种多酚酸对H2O2诱导小鼠肝匀浆脂质过氧化的保护作用强弱依次为迷迭香酸咖啡酸原儿茶醛绿原酸阿魏酸丹参素3-羟基肉桂酸,其最大和最小抑制率相差2.4倍;对小鼠肝脏组织自发脂质过氧化的抑制率大小顺序为迷迭香酸、原儿茶醛、绿原酸、咖啡酸、阿魏酸、丹参素、3-羟基肉桂酸,最高和最低抑制率相差近90%。7种天然有机酸抗脂质过氧化作用因化合物结构不同存在显著差异。     

HPLC法测定紫苏不同来源不同部位中迷迭香酸的含量

采用 HP LC 法测定14种不同来源紫苏不同部位的迷迭香酸的含量,并进行统计与聚类分析.结果表明：14种来源紫苏间叶、果穗、茎及根中迷迭香酸含量均有显著差异(P ＜0．05),同一来源不同部位间迷迭香酸含量也存在显著差异(P ＜0．05).各种来源紫苏叶中的迷迭香酸含量均最高;大部分来源紫苏果穗中迷迭香酸的含量较紫苏茎高.14份材料经聚类分析可分成4个类群.研究结果表明紫苏果穗可能是潜在的新药源,来源于长江中下游紫苏不同部位的迷迭香酸含量要比西南地区的高.     

基于丹参基因组的迷迭香酸合成酶的生物信息学分析

丹参是我国常用大宗中药材,丹酚酸B是其水溶性药效成分的代表,迷迭香酸是丹酚酸B等复杂活性物质的核心结构单元,迷迭香酸合成酶承担着催化迷迭香酸生物合成的重要作用。因此,解析丹参迷迭香酸合成酶的生物学功能,对研究迷迭香酸和丹酚酸B生物合成,促进丹参品质改善具有重要作用。本研究利用生物信息学方法,从丹参基因组库中寻找到11条迷迭香酸合成酶编码基因,并对其进行了生物信息学分析。丹参迷迭香酸合成酶属于BAHD酰基转移酶家族,分子量在36 kD至59 kD之间,多为酸性稳定蛋白,不含信号肽和导肽,无规则卷曲和α-螺旋是其二级结构的主要特征。本研究对丹参迷迭香酸合成酶进行了详细的生物信息学分析,可为今后深入研究该酶的结构特征和功能提供参考。     

肾草酸钙结石模型的制作及迷迭香酸对病模的影响

目的:观察以1%乙二醇+2%氯化铵配成的造石液制作大鼠肾草酸钙结石病模的表现,同时试验迷迭香酸对此病模的影响,为今后研究抗肾草酸钙结石的药物提供可靠的模型。方法:以1%乙二醇+2%氯化铵配成的造石液每天灌胃,连续28天,诱导大鼠草酸钙晶体形成,建立大鼠肾草酸钙结石模型,采用全自动生化分析仪测定大鼠尿生化、血生化,解剖取双肾,测定肾组织草酸、枸橼酸等指标。结果:模型组的尿生化、血生化、肾组织草酸均显著高于空白对照组、迷迭香酸组(P<0.01)。结论:以1%乙二醇+2%氯化铵成功建立大鼠肾草酸钙结石模型,迷迭香酸对结石病模有非常明显改善作用。应用此模型,对受试药物进行实验研究。     

薄荷中迷迭香酸的分离提取及含量测定

本文对薄荷中的迷迭香酸进行了分离提取及含量测定研究。以水为溶剂,热回流浸提,采用硫酸亚铁比色法对薄荷中的迷迭香酸进行定性分析,用高效液相色谱法进行含量测定,得到薄荷中的迷迭香酸的含量为0．156％。该法准确度高,结果稳定。     

Study of antioxidant and membrane activity of rosmarinic acid using different model systems

Rosmarinic acid is found in many species of different families of higher plants and its chemical structure is phenol propanoid with various biological activity. In this paper, we conducted a comparative study of antioxidant (radical-scavenging) properties of rosmarinic acid in systems of 2,2tāzo-bis(2-methylpropionamidin)dihydrochloride-luminol and hemoglobin-hydrogen peroxide-luminol, determined its protective potential in preventing peroxidation of linoleic acid, and evaluated the effect on the permeability of planar bilayer lipid membranes. Linoleic acid peroxidation was assessed by iron-thiocyanate method. In these studies, trolox was used as a reference antioxidant, and ascorbic acid, and dihydroquercetin were taken as standards. Rosmarinic acid is significantly superior to trolox, ascorbic acid and dihydroquercetin in the tests for antioxidant activity in the systems studied, as well as in inhibition of linoleic acid peroxidation. According to their activity the investigated substances can be arranged in the following order: rosmarinic acid > dihydroquercetin trolox > ascorbic acid. Rosmarinic acid does not cause significant changes in the permeability of planar bilayer membranes in a dose range of 0.5 to 10 μg/mL. Antioxidant activity of rosmarinic acid is due to the neutralization of reactive oxygen species and/or luminol radicals generated in model systems. The observed features of the antioxidant and membrane activity of rosmarinic acid, which may underlie the previously mentioned pharmacological effects are discussed.     

Rosmarinic acid inhibits lung injury induced by diesel exhaust particles

Epidemiological and experimental studies have suggested that diesel exhaust particles (DEP) may be involved in recent increases in lung diseases. DEP has been shown to generate reactive oxygen species. Intratracheal instillation of DEP induces lung inflammation and edema in mice. Rosmarinic acid is a naturally occurring polyphenol with antioxidative and anti-inflammatory activities. We investigated the effects of rosmarinic acid on lung injury induced by intratracheal administration of DEP (500 microg/body) in mice. Oral supplementation with administration of rosmarinic acid (2 mg/body for 3 d) inhibited DEP-induced lung injury, which was characterized by neutrophil sequestration and interstitial edema. DEP enhanced the lung expression of keratinocyte chemoattractant (KC), interleukin-1beta, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1alpha, which was inhibited by treatment with rosmarinic acid. DEP enhanced expression of iNOS mRNA and formation of nitrotyrosine and 8-OHdG in the lung, which was also inhibited by rosmarinic acid. These results suggest that rosmarinic acid inhibits DEP-induced lung injury by the reduction of proinflammatory molecule expression. Antioxidative activities of rosmarinic acid may also contribute to its protective effects.     

The effects of rosmarinic acid on oxidative stress parameters and inflammatory cytokines in lipopolysaccharide-induced peripheral blood mononuclear cells

Molecular Biology Reports - Rosmarinic acid (RA) is a potential herbal medicine and has received considerable attention due to its strong antioxidant properties. The aim of this study is to...     

Rosmarinic acid

Rosmarinic acid is an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid. It is commonly found in species of the Boraginaceae and the subfamily Nepetoideae of the Lamiaceae. However, it is also found in species of other higher plant families and in some fern and hornwort species. Rosmarinic acid has a number of interesting biological activities, e.g. antiviral, antibacterial, antiinflammatory and antioxidant. The presence of rosmarinic acid in medicinal plants, herbs and spices has beneficial and health promoting effects. In plants, rosmarinic acid is supposed to act as a preformed constitutively accumulated defence compound. The biosynthesis of rosmarinic acid starts with the amino acids L-phenylalanine and L-tyrosine. All eight enzymes involved in the biosynthesis are known and characterised and cDNAs of several of the involved genes have been isolated. Plant cell cultures, e.g. from Coleus blumei or Salvia officinalis, accumulate rosmarinic acid in amounts much higher than in the plant itself (up to 36% of the cell dry weight). For this reason a biotechnological production of rosmarinic acid with plant cell cultures has been proposed.     

Rosmarinic acid inhibits some metabolic enzymes including glutathione S-transferase,lactoperoxidase, acetylcholinesterase,butyrylcholinesterase and carbonic anhydrase isoenzymes

Rosmarinic acid (RA) is a natural polyphenol contained in many aromatic plants with promising biological activities. Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread and intensively studied metalloenzymes present in higher vertebrates. Acetylcholinesterase (AChE, E.C. 3.1.1.7) is intimately associated with the normal neurotransmission by catalysing the hydrolysis of acetylcholine to acetate and choline and acts in combination with butyrylcholinesterase (BChE) to remove acetylcholine from the synaptic cleft. Lactoperoxidase (LPO) is an enzyme involved in fighting pathogenic microorganisms, whereas glutathione S-transferases (GSTs) are dimeric proteins present both in prokaryotic and in eukaryotic organisms and involved in cellular detoxification mechanisms. In the present study, the inhibition effects of rosmarinic acid on tumour-associated carbonic anhydrase IX and XII isoenzymes, AChE, BChE, LPO and GST enzymes were evaluated. Rosmarinic acid inhibited these enzymes with K_is in the range between micromolar to picomolar. The best inhibitory effect of rosmarinic acid was observed against both AChE and BChE.     

Molecular docking analysis of SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) with compounds from Plectranthus amboinicus

It is of interest to document the moelcular docking analysis of SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) with compounds from Plectranthus amboinicus. Hence, we report the binding features of rutin, Luteolin, Salvianolic acid A, Rosmarinic acid and p-Coumaric acid with the target protein SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) for further consideration.     

Anti‐invasion effect of rosmarinic acid via the extracellular signal‐regulated kinase and oxidation–reduction pathway in Ls174‐T cells

Rosmarinic acid is a major phenylpropanoid isolated from Prunella vulgaris L., which is a composition of herbal tea for centuries in China. However, the anti‐invasion activity on Ls174‐T human colon carcinoma cells has not been studied. In this study, we investigated the anti‐metastasis functions according to wound healing assay, adhesion assay, and Transwell assay and found that rosmarinic acid could inhibit migration, adhesion, and invasion dose‐dependently. Rosmarinic acid also could decrease the level of reactive oxygen species by enhancing the level of reduced glutathione hormone. In addition, rosmarinic acid repressed the activity and expression of matrix metalloproteinase‐2,9. According to Western blot and quantitative real‐time PCR assay, rosmarinic acid may inhibit metastasis from colorectal carcinoma mainly via the pathway of extracellular signal‐regulated kinase. In animal experiment, intraperitoneal administration of 2 mg of rosmarinic acid reduced weight of tumors and the number of lung nodules significantly compared with those of control group. Therefore, these results demonstrated that rosmarinic acid can effectively inhibit tumor metastasis in vitro and in vivo. J. Cell. Biochem. 111: 370–379, 2010. © 2010 Wiley‐Liss, Inc.     

Pharmacology of rosemary (Rosmarinus officinalis Linn.) and its therapeutic potentials

The use of plants is as old as the mankind. Natural products are cheap and claimed to be safe. They are also suitable raw material for production of new synthetic agents. Rosemary (Rosmarinus officinalis Linn.) is a common household plant grown in many parts of the world. It is used for flavouring food, a beverage drink, as well as in cosmetics; in folk.medicine it is used as an antispasmodic in renal colic and dysmenorrhoea, in relieving respiratory disorders and to stimulate growth of hair. Extract of rosemary relaxes smooth muscles of trachea and intestine, and has choleretic, hepatoprotective and antitumerogenic activity. The most important constituents of rosemary are caffeic acid and its derivatives such as rosmarinic acid. These compounds have antioxidant effect. The phenolic compound, rosmarinic acid, obtains one of its phenolic rings from phenylalanine via caffeic acid and the other from tyrosine via dihydroxyphenyl-lactic acid. Relatively large-scale production of rosmarinic acid can be obtained from the cell culture of Coleus blumei Benth when supplied exogenously with phenylalanine and tyrosine. Rosmarinic acid is well absorbed from gastrointestinal tract and from the skin. It increases the production of prostaglandin E2 and reduces the production of leukotriene B4 in human polymorphonuclear leucocytes, and inhibits the complement system. It is concluded that rosemary and its constituents especially caffeic acid derivatives such as rosmarinic acid have a therapeutic potential in treatment or prevention of bronchial asthma, spasmogenic disorders, peptic ulcer, inflammatory diseases, hepatotoxicity, atherosclerosis, ischaemic heart disease, cataract, cancer and poor sperm motility.     

不同品种和生长年限对丹参产量及有效成分积累动态的影响

同时提高丹参经济产量(根系干重)及有效成分积累是当前丹参栽培的热点及难点。通过不同品种和生长年限丹参的田间小区栽培试验,测定不同采收期丹参根系干重,脂溶性成分含量(丹参酮I,隐丹参酮和丹参酮IIA)和水溶性成分含量(原儿茶醛,原儿茶酸,丹酚酸B和迷迭香酸),研究品种、生长年限、采收期对丹参经济产量和有效成分积累的影响,以期为丹参规范化种植提供依据。无论从经济产量,还是脂溶性成分和水溶性成分产量(根系产量×含量),两年生丹参均优于第一年生。丹参脂溶性成分含量在9月份达到最高,而水溶性成分含量除迷迭香酸外在11月份达到最高值。由于收获前丹参根系的快速生长,无论是水溶性还是脂溶性成分,其有效成分产量均在收获期(11月4日)达到最高。不同品种丹参品种的经济产量及有效成分存在较大差异,生产中应有针对性的选择丹参品种。     

Rosmarinic acid down-regulates the LPS-induced production of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) via the MAPK pathway in bone-marrow derived dendritic cells

In the present study, we investigated whether rosmarinic acid, which has been suggested to exhibit anti-inflammatory properties, can suppress the expressions of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) via the MAPK pathway in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) in the presence of GM-CSF and IL-4 in media. The effects of rosmarinic acid were investigated in BMDCs with respect to the following; cytotoxicity, surface molecule expression, dextran-FITC uptake, cell migration, chemokine gene expression, and the MAPK signaling pathway. Rosmarinic acid was found to significantly inhibit the expressions of CD80, CD86, MHC class I, and MHC class II in LPS-stimulated mature BMDCs, and rosmarinic acid-treated BMDCs were found to be highly efficient with regards to antigen capture via mannose receptor-mediated endocytosis. In addition, rosmarinic acid reduced cell migration by inducing the expression of a specific chemokine receptor on LPS-induced mature BMDCs. Rosmarinic acid also significantly reduced the expressions of MCP-1 and MIP-lalpha induced by LPS in BMDCs and inhibited LPS-induced activation of MAPK and the nuclear translocation of NF-kappaB. These findings broaden current perspectives concerning our understanding of the immunopharmacological functions of rosmarinic acid, and have ramifications that concern the development of therapeutic drugs for the treatment of DC-related acute and chronic diseases.