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HPPR encodes the hydroxyphenylpyruvate reductase required for the biosynthesis of hydrophilic phenolic acids in salvia miltiorrhiza

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Chinese Journal of Natural Medicines 2017年第12期15卷 917-927页

作者： WANG Guo-Quan CHEN Jun-Feng YI Bo TAN He-Xin ZHANG Lei CHEN Wan-Sheng School of Biomedical Sciences Huaqiao University Department of Pharmaceutical Botany School of Pharmacy Second Military Medical University Department of Pharmacy Changzheng Hospital Second Military Medical University

salvia miltiorrhiza is a medicinal plant widely used in the treatment of cardiovascular and cerebrovascular diseases. Hydrophilic phenolic acids, including rosmarinic acid(RA) and lithospermic acid B(LAB), are its primary medicinal ingredients. However, the biosynthetic pathway of RA and LAB in S. miltiorrhiza is still poorly understood. In the present study, we accomplished the isolation and characterization of a novel S. miltiorrhiza Hydroxyphenylpyruvate reductase(HPPR) gene, Sm HPPR, which plays an important role in the biosynthesis of RA. Sm HPPR contained a putative catalytic domain and a NAD(P)H-binding motif. The recombinant Sm HPPR enzyme exhibited high HPPR activity, converting 4-hydroxyphenylpyruvic acid(p HPP) to 4-hydroxyphenyllactic acid(p HPL), and exhibited the highest affinity for substrate 4-hydroxyphenylpyruvate. Sm HPPR expression could be induced by various treatments, including SA, GA_3, Me JA and Ag^+, and the changes in Sm HPPR activity were correlated well with hydrophilic phenolic acid accumulation. Sm HPPR was localized in cytoplasm, most likely close to the cytosolic NADPH-dependent hydroxypyruvate reductase active in photorespiration. In addition, the transgenic S. miltiorrhiza hairy roots overexpressing Sm HPPR exhibited up to 10-fold increases in the products of hydrophilic phenolic acid pathway. In conclusion, our findings provide a new insight into the synthesis of active pharmaceutical compounds at molecular level.

关键词： salvia miltiorrhiza Hydrophilic phenolic acids Rosmarinic acid Llithospermic acid B Biosynthesis pathway

What are the best salvia miltiorrhiza injection classes for treatment of unstable angina pectoris? A systematic review and network Meta-analysis

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Journal of Traditional Chinese Medicine 2018年第3期38卷 321-338页

作者： Liu Shi Wu Jiarui Zhang Dan Tan Di Department of Clinical Pharmacology of Traditional Chinese Medicine School of Chinese Materia Medica Beijing University of Chinese Medicine

OBJECTIVE: To undertake a systematic review and network meta-analysis(NMA) to compare the effectiveness among the different regimens of salvia miltiorrhiza injection classes(SMICs) for unstable angina pectoris(UAP) ***: A systematic retrieval was conducted in several literature databases to identify randomized controlled trials focusing on the different regimens of SMICs for UAP treatment until January2016. The quality assessment was accomplished according to the Cochrane risk of bias tool. Pair-wise meta-analyses were carried out by Rev Man 5.3. A random-effects model of NMA was used to compare the different regimens of SMICs with regard to efficacy by STATA ***: A total of 111 studies involving 10 500patients were included in the NMA. The methodological quality of included studies was not *** evidence shows that salvianolate(SI) is the optimal treatment for UAP in improving the total efficacy against UAP. Guanxingning(GXN) is the optimal treatment for UAP for improving the total effectiveness of ***: SMICs have advantages in preventing cardiovascular events. GXN, SI, and Danhong had the greatest probability of being the best treatment in the total efficacy against UAP and for improving the total effectiveness of electrocardiography.

关键词： salvia miltiorrhiza Angina unstable Re-view Network Meta-analysis

A Comparative Analysis of the Chloroplast Genomes of Four salvia Medicinal Plants

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Engineering 2019年第5期5卷 907-915页

作者： Conglian Liang Lei Wang Juan Lei Baozhong Duan Weisi Ma Shuiming Xiao Haijun Qi Zhen Wang Yaoqi Liu Xiaofeng Shen Shuai Guo Haoyu Hu Jiang Xu Shilin Chen College of Pharmacy Shandong University of Traditional Chinese Medicine(TCM)Jinan 250355China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China State Key Laboratory of Innovative Natural Medicine and TCM Injections Jiangxi Qingfeng Pharmaceutical Co.Ltd.Ganzhou 341000China Beijing Children’s Hospital Capital Medical UniversityNational Center for Children’s HealthBeijing 100045China School of Biological Science The University of QueenslandBrisbaneQLD 4072Australia College of Pharmacy Dali UniversityDali 671000China Institute of Medicinal Plants Yunnan Academy of Agricultural SciencesKunming 650205China

Herbgenomics is an emerging field of traditional Chinese medicine(TCM)research and *** combining TCM research with genomics,herbgenomics can help to establish the scientific validity of TCM and bring it into wider usage within the field of *** Linn.(***.)is a large genus of Labiatae that includes important medicinal *** this herbgenomics study,the complete chloroplast(cp)genomes of two salvia spp.—namely,*** and ***,which are used as a surrogate for ***—were sequenced and compared with those of two other reported salvia spp.—namely,*** and *** genome organization,gene number,type,and repeat sequences were *** annotation results showed that both salvia plants contain 114 unique genes,including 80 protein-coding,30 transfer RNA(tRNA),and four ribosomal RNA(rRNA)*** sequence analysis revealed 21 forward and 22 palindromic sequences in both salvia cp genomes,and 17 and 21 tandem repeats in *** and ***,respectively.A synteny comparison of the salvia *** genomes showed a high degree of sequence similarity in the coding regions and a relatively high divergence of the intergenic *** alignment and single-nucleotide polymorphism(SNP)analyses found some candidate fragments to identify salvia spp.,such as the intergenic region of the trnV–ndhC,trnQ–rps16,atpI–atpH,psbA–ycf3,ycf1,rpoC2,ndhF,matK,rpoB,rpoA,and accD *** of the results—including the repeat sequences and SNP sites,the inverted repeat(IR)region border,and the phylogenetic analysis—showed that *** and *** are extremely similar from a genetic *** cp genome sequences of the two salvia *** here will pave the way for breeding,species identification,phylogenetic evolution,and cp genetic engineering studies of salvia medicinal plants.

关键词： salvia Chloroplast genome Comparative analysis

Short-term effect of salvia miltiorhiza in treating rat acetic acid chronic gastric ulcer and long-term effect in preventing recurrence

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World Journal of Gastroenterology 1998年第2期4卷 77-78页

作者： Wang, GZ Ru, X Ding, LH Li, HQ First Affiliated Hosp Qiqihaer Med Coll Dept Pathophysiol Qiqihaer 161042 Heilongjiang Peoples R China First Affiliated Hosp Qiqihaer Med Coll Dept Surg Qiqihaer 161042 Heilongjiang Peoples R China China Med Univ Dept Pathophysiol Shenyang 110001 Liaoning Peoples R China

ＳｈｏｒｔｔｅｒｍｅｆｅｃｔｏｆＳａｌｖｉａｍｉｌｔｉｏｒｈｉｚａｉｎｔｒｅａｔｉｎｇｒａｔａｃｅｔｉｃａｃｉｄｃｈｒｏｎｉｃｇａｓｔｒｉｃｕｌｃｅｒａｎｄｌｏｎｇｔｅｒｍｅｆｅｃｔｉｎｐｒｅｖｅｎｔｉｎｇｒｅｃ... 详细信息

ＳｈｏｒｔｔｅｒｍｅｆｅｃｔｏｆＳａｌｖｉａｍｉｌｔｉｏｒｈｉｚａｉｎｔｒｅａｔｉｎｇｒａｔａｃｅｔｉｃａｃｉｄｃｈｒｏｎｉｃｇａｓｔｒｉｃｕｌｃｅｒａｎｄｌｏｎｇｔｅｒｍｅｆｅｃｔｉｎｐｒｅｖｅｎｔｉｎｇｒｅｃｕｒｅｎｃｅＷＡＮＧＧｕｏＺｈｏ...

关键词： Danshen disease models, animal salvia miltiorrhiza stomach ulcer acetic acid cimitidine gastric mucosa recurrence rats , Wistar chronic diseases

Anticancer activity of salvia officinalis essential oil and its principal constituents against hormone-dependent tumour cells

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Asian Pacific Journal of Tropical Biomedicine 2019年第1期9卷 24-28页

作者： G.Privitera T.Luca S.Castorina R.Passanisi G.Ruberto E.Napoli Fondazione Mediterranea "G.B.Morgagni" Department of Medical and Surgical Sciences and advanced technologies University of Catania Institute of Biomolecular Chemistry Italian National Research Council ICB-CNR

Objective: To investigate the in vitro antiproliferative action of essential oil from salvia officinalis L.(S. officinalis) grown in Sicily(Italy), and its main components on hormone-dependent cancer cell lines. Methods: S. officinalis essential oil was prepared by hydrodistillation. The actions of the S. officinalis essential oil and its three principal components(毩-thujone, 1,8-cineole and camphor) were evaluated in LNCaP cells(prostate carcinoma), MCF7 cells(breast carcinoma) and He La cells(cervical carcinoma) at various dosages and diverse time points. Cell viability and proliferation were estimated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results: S. officinalis essential oil at doses of 100 μg/m L and 200 μg/m L induced a significant reduction of cell viability in MCF7, LNCa P and He La cell lines after a 48-hour incubation. The same cell lines also showed decreased cell viability when they were treated with a mixture of three major components of the essential oil, at doses of 100 μg/mL and 200 μg/mL, after a 48-hour incubation. Conclusions: These preliminary results could shed light on the formulation of new therapeutic agents with antiproliferative activity. Thus supplementary investigations are fundamental to examine the molecular mechanisms of the anticancer effects of this species of salvia in cancer cells and to achieve confirmation of its in vivo anticancer activity.

关键词： Antiproliferative activity Hormone-dependent cancers Essential oil salvia officinalis

Generation and analysis of expressed sequence tags from the medicinal plant salvia miltiorrhiza

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Science China(Life Sciences) 2010年第2期53卷 273-285页

作者： SPENCER David F Department of Biochemistry and Molecular Biology Dalhousie University

salvia miltiorrhiza *** a well-known traditional Chinese *** roots have been formulated and used clinically for the treatment of various ***,little genetic information has so far been available and this fact has become a major obstacle for molecular *** address this lack of genetic information,an Expressed Sequence Tag (EST) library from whole plantlets of *** was *** the 12959 cDNA clones that were randomly selected and subjected to single-pass sequencing from their 5′ ends,10288 ESTs (with sizes≥100 bp) were selected and assembled into 1288 contigs,leaving 2937 singletons,for a total of 4225 *** were analyzed using BLASTX (against protein databases),RPS-BLAST (against a conserved domain database) as well as the web-based KEGG Automatic Annotation Server for metabolic enzyme *** on the metabolic enzyme assignment,expression patterns of 14 secondary metabolic enzyme genes in different organs and under different treatments were verified using real-time PCR ***,a total of 122 microsatellites were identified from the ESTs,with 89 having sufficient flanking sequences for primer *** set of ESTs represents a significant proportion of the *** transcriptome,and gives preliminary insights into the gene complement of *** will prove useful for uncovering secondary metabolic pathways,analyzing cDNA-array based gene expression,genetic manipulation to improve yield of desirable secondary products,and molecular marker identification.

关键词： expressed sequence tags salvia miltiorrhiza Bge. gene identification microsatellite

An ethnopharmacological investigation of medicinal salvia plants (Lamiaceae) in China

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Acta Pharmaceutica Sinica B 2013年第4期3卷 273-280页

作者： Minhui Li Qianquan Li Chunhong Zhang Na Zhang Zhanhu Cui Luqi Huang Peigen Xiao National Resource Center for Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Baotou Medical College Baotou 014060China School of Chinese Pharmacy Beijing University of Chinese MedicineBeijing 100102China Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100193China

In China,over 40 species of the genus salvia have been used as medicinal plants for various diseases,some for thousands of ***,research has focused on the biological activities of salvia medicinal plants used in traditional chinese medicine(TCM).However,to date a scientific survey of the genus salvia in China has not been carried *** this paper,we report the results of 10 field surveys of salvia medicinal plants collected in 17 provinces including detailed information on their local names,growing environment,distribution and therapeutic *** also summarize the results of research on the materia medica,phytochemistry and pharmacology of some of the important salvia medicinal *** study reveals that 35 salvia plants have been used in TCM in different regions of China,including 20 species used as Danshen to treat heart diseases,and 15 species used to treat a range of other conditions including gynecological diseases,muscular or skeletal problems,hepatitis,urological diseases,and mouth and eye *** is clear that some species of salvia *** significant pharmacological activity in the context of ethnopharmacological knowledge,especially in the treatment of heart *** studies of the phytochemistry and pharmacology of salvia species will no doubt improve their medical utilization and contribute to the development of new natural drugs.

关键词： salvia Ethnopharmacology Medicinal plants Danshen

salvia fruticosa reduces intrinsic cellular and H_2O_2-induced DNA oxidation in HEK 293 cells;assessment using flow cytometry

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Asian Pacific Journal of Tropical Biomedicine 2014年第5期4卷 399-403页

作者： Saleem Bani Hani Mekki Bayachou Department of Medical laboratory Sciences Jordan University of Science and Technology Department of Chemistry Cleveland State University

Objective:To investigate the role of water-soluble extract of salvia fruticosa(Creek sage)(***) leaves in reducing both intrinsic cellular and H_2O_2-induced DNA oxidation in cultured human embryonic kidney 293 *** to the Eastern-Mediterranean basin,is widely used as a medicinal herb for treatment of various ***:Dried leaves of *** were extracted in phosphate buffer saline and purified using both vacuum and high pressure *** mL of the preparation contained(7.1±1.0)mg of ***-293 cells were incubated in one set with *** extract in the presence of 0.1 mmol/L H_2O_2,and in the other set with the addition of the extract *** DNA oxidation was measured using fluorescence upon fluorescein isothiocyanate derivarization of 8-oxoguanine *** fluorescence was measured using flow cytometry ***:Cells incubated 3 h with 150μL extract and exposed to 0.1 mmol/L H_2O_2 showed lower intensity of fluorescence,and thus lower DNA ***,cells incubated 3 h with 100μ*** the extract showed lower intensity of fluorescence,and thus lower intrinsic cellular DNA oxidation compared to control(without ***).Conchisions:The results from this study suggest that the water-soluble extract of *** leaves protects against both H_2O_2-induced and intrinsic cellular DNA oxidation in human embryonic kidney 293 cells.

关键词： salvia fruticosa DNA oxidation Oxidative stress Human embryonic kidney 293 cells Flow cytometry

Cardioprotective effects of salvia miltiorrhiza Bunge and Lignum dalbergiae odoriferae on rat myocardial ischemia/reperfusion injury

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中国药理学通报 2015年第B11期31卷 168-169页

作者： MUFei DUANJia-lin BIANHai-xu YINYing ZHUYan-rong WEIGuo GUOCHao WENAi-dong XIMIAO-miao DepartmentofPharmacy XijingHospitalFouthMilitaryMedicalUniversityXi'anShanxi710032

Aim salvia miltiorrhiza Bunge （SM） and lignum dalbergiae odoriferae （DO） are both traditional Chi- nese medicine that have cardioprotective effects. Here, we further examined the combined effects of SM and DO on rat myocardial ischemia/reperfusion injury. The possible mechanism of SM and DO also were elucidated. Methods DO was divided into aqueous extract of lignum dalbergiae odoriferae （DOW） and lignum dalbergiae odoriferae oil （DOO）. Sprague-Dawley rats were randomized to seven groups： sham group, model group, treatment groups inclu- ding SM （10 g · kg^-1）, DOW （5 g · kg^-1）, DOO （0.5 ml · kg^-1）, SM ＋ DOW （10 g · kg^-1 ＋ 5 g · kg^-1）, SM ＋ DOO （ 10 g · kg^-1 ＋ 0. 5 ml · kg^-1）. Rats were pretreated with homologous drug for 7 days and then subjec- ted to 30 rain of ischemia followed by 180 rain of reperfusion. Electrocardiogram （ECG） and heart rate were moni- tored and recorded continuously. At the end of reperfusion, blood samples were collected to determine the serum levels of creatine kinase-MB （CK-MB） and lactate dehydrogenase （LDH）. Hearts were harvested to assess heart- body rate, infarct size and histopathological changes as well. Maximum and minimum effective points were deter- mined by measuring indicators associate with myocardial injury at different time-points of reperfusion （Smin, 15min, 30min, 45rain, 60min, 120min, 180min）. The potential therapeutic mechanism of SM and SM ＋ DOO were carried out by detecting superoxide dismutase （SOD）, malondialdehyde （MDA）, tumor necrosis factor-alpha （TNF-alpha） and interleukin 6 （IL-6）. Results The results showed SM and DO can ameliorate cardiac function respectively, and this cardioprotective effect was further strengthened by their combinations. Among all the combi- nations, SM ＋ DOO showed predominant potential to improve ECG and heart rate, reduce heart-body rate （28.5% ＋ 1.4% , P 〈 0.01 vs model） and myocardial infarct size （ 20.96% ＋ 1.61% , P 〈 0.01 vs model, P 〈 0.05 vs SM） , attenuate histopathological

关键词： Keywords:myocardialischemia/reperfusioninjury salviamiltiorrhizaBunge Lignumdalbergiaeodoriferae the myocardial ischemia/reperfusion injury salvia miltiorrhiza Bunge Lignum dalbergiae odoriferae themaximum and minimum effective points anti-oxidant anti-inflammatory