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rosmarinic acid elicits neuroprotection in ischemic stroke via Nrf2 and heme oxygenase 1 signaling

Neural Regeneration Research 2018年第12期13卷 2119-2128页

作者： Hai-Ying Cui Xiang-Jian Zhang Yi Yang Cong Zhang Chun-Hua Zhu Jiang-Yong Miao Rong Chen Department of Neurology Second Hospital of hebei Medical university Shijiazhuang Hebei Province China Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardiocerebrovascular Disease ShijiazhuangHebei Province China

rosmarinic acid（RA） can elicit a neuroprotective effect against ischemic stroke, but the precise molecular mechanism remains poorly understood. In this study, an experimental ischemic stroke model was established in CD-1 mice（Beijing Vital River Laboratory Animal Technology, Beijing, China） by occluding the right middle cerebral artery for 1 hour and allowing reperfusion for 24 hours. After intraperitoneally injecting model mice with 10, 20, or 40 mg/kg RA, functional neurological deficits were evaluated using modified Longa scores. Subsequently, cerebral infarct volume was measured using TTC staining and ischemic brain tissue was examined for cell apoptosis with TUNEL staining. Superoxide dismutase activity and malondialdehyde levels were measured by spectrophometry. Expression of heme oxygenase-1（HO-1）, nuclear factor erythroid 2-related factor 2（Nrf2）, Bcl-2, Bax, Akt, and phospho-Ser473 Akt proteins in ischemic brain tissue was detected by western blot, while mRNA levels of Nrf2, HO-1, Bcl-2, and Bax were analyzed using real time quantitative PCR. In addition, HO-1 enzyme activity was measured spectrophotometrically. RA（20 and 40 mg/kg） greatly improved neurological function, reduced infarct volume, decreased cell apoptosis, upregulated Bcl-2 protein and mRNA expression, downregulated Bax protein and mRNA expression, increased HO-1 and Nrf2 protein and mRNA expression, increased superoxide dismutase activity, and decreased malondialdehyde levels in ischemic brain tissue of model mice. However, intraperitoneal injection of a HO-1 inhibitor（10 mg/kg zinc protoporphyrin IX） reversed the neuroprotective effects of RA on HO-1 enzyme activity and Bcl-2 and Bax protein expression. The PI3 K/Akt signaling pathway inhibitor LY294002（10 mM） inhibited Akt phosphorylation, as well as Nrf2 and HO-1 expression. Our findings suggest that RA has anti-oxidative and anti-apoptotic properties that protect against ischemic stroke by a mechanism involving upregulation of Nrf2 and HO

关键词： cerebral ischemia/reperfusion rosmarinic acid cellular apoptosis oxidative injury neuroprotection Bcl-2 Bax Nrf2 heme oxygenase 1 PI3K/Akt signal pathway neural regeneration

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rosmarinic acid attenuates hepatic fibrogenesis via suppression of hepatic stellate cell activation/proliferation and induction of apoptosis

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Asian Pacific Journal of Tropical Medicine 2017年第5期10卷 423-432页

作者： Naglaa M.El-Lakkany Walaa H.El-Maadawy Sayed H.Seif el-Din Olfat A.Hammam Salwa H.Mohamed Shahira M.Ezzat Marwa M.Safar Samira Saleh Department of Pharmacology Theodor Bilharz Research InstituteWarak El-HadarImbaba P.O.Box 30Giza 12411Egypt Department of Pathology Theodor Bilharz Research InstituteWarak El-HadarImbaba P.O.Box 30Giza 12411Egypt Department of Immunology Theodor Bilharz Research InstituteWarak El-HadarImbaba P.O.Box 30Giza 12411Egypt Department of Pharmacognosy Faculty of PharmacyCairo UniversityCairo 11562Egypt Department of Pharmacology and Toxicology Faculty of PharmacyCairo UniversityCairo 11562Egypt

Objective:To investigate the antifibrotic role of rosmarinic acid(RA),a natural polyphenolic compound,on HSCs activation/proliferation and apoptosis in vitro and in vivo. Methods:The impact of RA on stellate cell line(HSC-T6) proliferation,activation and apoptosis was assessed along with its safety on primary hepatocytes. In vivo,rats were divided into:(i) normal;(ii) thioacetamide(TAA)-intoxicated rats for 12 weeks;(iii) TAA+silymarin or(iv) TAA+RA. At the end of experiment,liver functions,oxidative stress,inflammatory and profibrogenic markers,tissue inhibitor metalloproteinases type-1(TIMP-1) and hydroxyproline(HP) levels were evaluated. Additionally,liver histopathology and immunohistochemical examinations of alpha-smooth muscle actin(α-SMA),caspase-3 and proliferation cellular nuclear antigen(PCNA) were determined. Results:RA exhibited anti-proliferative effects on cultured HSCs in a time and concentration dependent manner showing an IC50 of 276 μg/mL and 171 μg/mL for 24 h and 48 h,respectively,with morphological reversion of activated stellate cell morphology to quiescent form. It significantly improved ALT,AST,oxidative stress markers and reduced TIMP-1,HP levels,inflammatory markers and fibrosis score(S1 vs S4). Furthermore,reduction in α-SMA plus elevation in caspase-3 expressions of HSCs in vitro and in vivo associated with an inhibition in proliferation of damaged hepatocytes were recorded. Conclusions:RA impeded the progression of liver fibrosis through inhibition of HSCs activation/proliferation and induction of apoptosis with preservation of hepatic architecture.

关键词： Hepatic fibrosis Hepatic stellate cells rosmarinic acid Apoptosis Proliferation Profibrogenic markers

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rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第3期14卷 100-105页

作者： Vahideh Abbasnia Mohsen Foadoddini Delaram Eslimi Esfahani Mohammad Reza Khazdair Shahrbanoo Oryan Department of Biology Payame Noor UniversityTehranIran Cardiovascular Diseases Research Center Birjand University of Medical SciencesBirjandIran Department of Animal Sciences Faculty of Biological SciencesKharazmi UniversityTehranIran

Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized ***:Rats were randomly divided into six groups:the control group,the asthmatic group,and the asthmatic groups treated with dexamethasone(1 mg/kg;oral gavage)or three doses of rosmarinic acid(0.5,1,and 2 mg/kg;oral gavage).For induction of asthma,rats received intraperitoneal injections and inhalation of *** 21 days,bronchoalveolar lavage fluid and lung samples were collected for histopathological ***,total and differential white blood cell counts were ***:The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic *** addition,rosmarinic acid reduced white blood cell count and the percentages of eosinophils,monocytes,and neutrophils while increasing the percentage of ***-induced lung pathological changes were significantly improved by treatment with rosmarinic ***:rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.

关键词： rosmarinic acid Asthma Ovalbumin Tracheal responsiveness Inflammation White blood cell

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An injectable conductive hydrogel with dual responsive release of rosmarinic acid improves cardiac function and promotes repair after myocardial infarction

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Bioactive Materials 2023年第11期29卷 132-150页

作者： Linghong Zhang Zhongwu Bei Tao Li Zhiyong Qian Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China Department of Pediatric Cardiac Surgery West China the Second HospitalSichuan UniversityChengdu610041China

Myocardial infarction (MI) causes irreversible damage to the heart muscle, seriously threatening the lives of patients. Injectable hydrogels have attracted extensive attention in the treatment of MI. By promoting the coupling of mechanical and electrical signals between cardiomyocytes, combined with synergistic therapeutic strategies targeting the pathological processes of inflammation, proliferation, and fibrotic remodeling after MI, it is expected to improve the therapeutic effect. In this study, a pH/ROS dual-responsive injectable hydrogel was developed by modifying xanthan gum and gelatin with reversible imine bond and boronic ester bond double crosslinking. By encapsulating polydopamine-rosmarinic acid nanoparticles to achieve on-demand drug release in response to the microenvironment of MI, thereby exerting anti-inflammatory, anti-apoptotic, and anti-fibrosis effects. By adding conductive composites to improve the conductivity and mechanical strength of the hydrogel, restore electrical signal transmission in the infarct area, promote synchronous contraction of cardiomyocytes, avoid induced arrhythmias, and induce angiogenesis. Furthermore, the multifunctional hydrogel promoted the expression of cardiac-specific markers to restore cardiac function after MI. The in vivo and in vitro results demonstrate the effectiveness of this synergistic comprehensive treatment strategy in MI treatment, showing great application potential to promote the repair of infarcted hearts.

关键词： Myocardial infarction Responsive hydrogel rosmarinic acid Conductivity Combined treatment

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Novel colorimetric,photothermal and up-conversion fluorescence triple-signal sensor for rosmarinic acid detection

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Chinese Chemical Letters 2023年第8期34卷 275-281页

作者： Yinyin Chen Xiujuan Yang Changfang Lu Zouping Yang Wei Wu Xianxiang Wang College of Agronomy Sichuan Agricultural UniversityChengdu 611130China College of Science Sichuan Agricultural UniversityChengdu 611130China State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China Chengdu 611130China

rosmarinic acid(RA)is promising as a natural and nontoxic food ***,many analysis methods for RA generally depend on large instruments and single signals for quantitative detection.A new upconversion fluorescence,colorimetric and photothermal multi-modal sensing strategy is developed for the quantification of RA.β-cyclodextrin(CD)modified citric acid(Cit)wrapped NaYF_(4):Yb/Er-Cit-CD(Y:Yb/Er-Cit-CD)up-conversion nanocomposite has been synthesized,which emits green fluorescence at 550nm under 980nm near-infrared(NIR)*** the presence of oxidized 3,3',5,5'-tetramethylbenzidine(oxTMB),the green fluorescence is significantly quenched attributed to the fluorescence inner filter effect(IFE)between oxTMB and Y:Yb/*** RA is intervened,blue oxTMB is reduced to colorless 3,3',5,5'-tetramethylbenzidine(TMB)inducing the recovery of up-conversion *** the same time,colorimetric and photothermal signals readout can be easily achieved thanks to the color indication and photothermal effect of the *** constructed Y:Yb/Er-Cit-CD/oxTMB sensor displays high sensitivity,visibility and simplicity for RA,and the limits of detection(LOD)for fluorescence,colorimetric and photothermal were 0.004μmol/L,0.036μmol/L and 0.043μmol/L,*** sensing system is successfully performed for the detection of RA in food samples.

关键词： Multi-modal sensing Up-conversion fluorescence Colorimetric Photothermal rosmarinic acid

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Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1661-1676页

作者： Junhui Chen Qian Zhang Jinan Guo Di Gu Jing Liu Piao Luo Yunmeng Bai Jiayun Chen Xinzhou Zhang Sheng Nie Chunbo Chen Yulin Feng Jigang Wang National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine Jiangxi University of Chinese MedicineNanchang 330006China Department of Pulmonary and Critical Care Medicine Shenzhen Institute of Respiratory Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalFirst Affiliated Hospital of Southern University of Science and TechnologySecond Clinical Medical College of Jinan UniversityShenzhen 518020China School of Traditional Chinese Medicine and School of Pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Urology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Nephrology Nanfang Hospitalthe First Affiliated Hospital of Southern Medical UniversityGuangzhou 510515China Department of Critical Care Medicine Shenzhen People's Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China State Key Laboratory for Quality Esurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Department of Oncology the Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and *** natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflammation and anti-oxidative-stress,in renal damage or *** this study,we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell *** results demonstrated that RA significantly alleviated renal tubular epithelial injury,particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes,while attenuating the inflammatory response of macrophages,oxidative stress,and cytotox-icity of natural killer *** findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage,oxidative stress,and inflammation,offering valuable guidance for the clinical application of RA in the treatment of DN.

关键词： rosmarinic acid Diabetic nephropathy scRNA sequencing Injury Oxidative stress Infiammation Proteomics

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Interactions of acetylcholinesterase with salvianolic acid B and rosmarinic acid from Salvia miltiorhiza water extract investigated by NMR relaxation rate

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Chinese Chemical Letters 2008年第6期19卷 747-751页

作者： GuoWei Yin Yi Ming Li Wei Wei Shan Hao Jiang Da Yuan Zhu Wei Hong Du Department of Chemistry Renmin University of China 59 Zhong Guan Cun Street Beijing 100872 China School of Pharmacy Shanghai University of Traditional Chinese Medicine 1200 Cailun Road Shanghai 201203 China State Key Laboratory for Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 555 Zuchongzhi Road Shanghai 201203 China

In order to understand whether the ameliorating effect on old ages memory disorder by the root of Salvia miltiorhiza is related to the acetylcholinesterase （ACHE） inhibition, two main ingredients, salvianolic acid B （1） and rosmarinic acid （2）, which were isolated from S. miltiorhiza water extract, were investigated in vitro by NMR relaxation rate in this work. The results showed that the proton selective relaxation rates and the molecular rotational correlation time of proton pairs for compounds 1 and 2 increased significantly by adding of AChE in mixing solution. The study reveals that the two compounds might bind to the enzyme and have ACHE inhibitory effect, which could contribute to the ameliorating effect at some extent on old ages memory disorder.

关键词： AChE inhibitors Salvianolic acid B rosmarinic acid NMR relaxation rate

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A New Homogenizing Technology to Obtain rosmarinic acid from Perilla Oil Meal

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Chinese Herbal Medicines 2012年第1期4卷 70-73页

作者： Wei-zhuo TANG[a] Yan-ze LIU[b][c] Yu-qing ZHAO[a][d] Shenyang Pharmaceutical University Shenyang 110016 China Bio-Organic and Natural Product Laboratory MRC 311 McLean Hospital/Harvard Medical School MA 02478 USA Institute of Medicinal Plant Development Chinese Academy of Medical Sciences Beijing 100193 Shenyang Pharmaceutical University Shenyang 110016 China Key Laboratory of Structure-Based Drug Design & Discovery Ministry of Education Shenyang Pharmaceutical University Shenyang 110016 China

Objective To optimize the extraction technology of the active component, rosmarinic acid, an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid, in perilla oil meal for the first time by a new homogenizing technology called smashing tissue extraction (STE). Methods Orthogonal design was used to optimize the extraction condition. The content of rosmarinic acid was quantified from the methanol crude extract with the help of HPLC. Results The optimization of STE process to get rosmarinic acid from the perilla oil meal was the ratio of liquid to solid material at 10:1 and the power of extraction at 150 V, extracting twice (2 min for each time). Conclusion STE could be applied to extracting the active ingredients from the oil meals due to its high extraction efficiency. This new homogenizing technology has advantages on saving extraction time, raising extraction efficiency, and maintaining the temperature sensitive constituents.

关键词： HPLC perilla oil meal rosmarinic acid smashing tissue extraction tissue homogenizing technology

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rosmarinic acid antagonized 1-methyl-4-phenylpyridinium(MPP+)-induced neurotoxicity in MES23.5 dopaminergic cells

Rosmarinic acid antagonized 1-methyl-4-phenylpyridinium(MPP+...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Ting-Ting DU,Lu LI,Ning SONG,Jun-Xia XIE,Luo-Xia LI,Tian LUO,Hong JIANG~* Department of Physiology,Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines:Physiology,Medical College of Qingdao University,Qingdao,266071

rosmarinic acid(RA) is a naturally polyphenolic compound in various plant *** previously reported that RA exerted protective effects against 6-OHDA-induced neurotoxicity through anti-oxidative properties. In this study,we investigate whether RA could antagonize against MPP insult in MES23.5 dopaminergic cells. MPP treatment caused decreased cell viability and dopamine content,and apoptotic morphological *** might be due to the MPP-induced mitochondria dysfunction,indicated by mitochondrial respiratory chain complexes I activity inhibition,mitochondrial transmembrane potential collapse and reactive oxygen species generation. Decreased Bcl-2/Bax ratio and caspase-3 activation could also be *** pretreatment could completely restore the mitochondrial respiratory chain complexes I activity,but partially reverse the other damaging effects of *** results indicate that RA plays a neuroprotective role by ameliorating mitochondrial dysfunction against MPP-induced cell apoptosis,and suggest that RA might be one of the candidates that could be clinically used for the prevention of Parkinson’s diseases.

关键词： rosmarinic acid MPP+ Parkinson’s disease apoptosis

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Algerian mint species:high performance thin layer chromatography quantitative determination of rosmarinic acid and in vitro inhibitory effects on linoleic acid peroxidation

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Journal of Coastal Life Medicine 2014年第12期 986-992页

作者： Brahmi Fatiha Madani Khodir Stévigny Caroline Chibane Mohamed Duez Pierre 13BS Laboratory Faculty of Natural Sciences and LifeUniversity of BejaiaBejaia 06000Algeria Laboratory of Pharmacognosy Bromatology and Human NutritionFaculty of PharmacyFree University of BelgiumCP 205-9B-1050 BrusselsBelgium Faculty of Natural Sciences and Life and Earth Sciences Akli Mohand Oulhadj UniversityBouira 10000Algeria Laboratory of Molecular Biology Institute of Health Sciences and TechnologyUniversity of Mons(UMONS)7000 MonsBelgium

Objective:To determine the quantitative paremeters of rosmarinic acid in Algerian mints,Mentha spicata L.(***),Mentha pulegium *** Mentha rotundifolia(L.)Huds by high performance thin layer chromatography(HPTLC)-densitometric method and screen the effects of these plant extracts on linoleic acid ***:The analyses were performed on HPTLC silica gel 60 F254 plates with chloroform:acetone:formic acid(75:16.5:8.5,v/v)as the mobile *** acid was determined in UV at 365 nm and fluorescence at λ_(exc)325 nm with a 550 nm filter,*** effects of plants extracts on linoleic acid peroxidation were measured by an indirect in vitro colorimetric ***:Chromatographic resolution permitted reliable quantification in both measurement modes and calibration curves were linear in a range of 150-1000 ng/*** was found to contain significantly higher concentrations of rosmarinic *** densitometric quantification allowed the analysis of many samples in a short time with reasonable precision(total precision for Mentha spp extracts,5.1%and 5.8%for UV and fluorescence detection,respectively).The HPTLC data,allied to assays of linoleic acid peroxidation prevention,suggested the potential of ***(52%Trolox®equivalents)as a natural source for inhibitors of lipid ***:Densitometry can be used for routine determination and quality control of rosmarinic acid in herbal and formulations containing Mentha species.

关键词： Densitometry High performance thin layer chromatography Lipid peroxidation Mentha sp rosmarinic acid

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