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Characteristics of Salvia miltiorrhiza methylome and the regulatory mechanism of DNA methylation in tanshinone biosynthesis

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Horticulture Research 2023年第7期10卷 265-279页

作者： Jiang Li Caili Li Yuxing Deng Hairong Wei Shanfa Lu Key Lab of Chinese Medicine Resources Conservation State Administration of Traditional Chinese Medicine of the People’s Republic of ChinaInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China Engineering Research Center of Chinese Medicine Resource Ministry of EducationBeijing 100193China College of Forest Resources and Environmental Science Michigan Technological UniversityHoughtonMI 49931USA

Salvia miltiorrhiza is a model medicinal plant with significant economic and medicinal *** roots produce a group of diterpenoid lipophilic bioactive components,termed *** and regulation of tanshinones has attracted widespread ***,the methylome of *** has not been analysed and the regulatory mechanism of DNA methylation in tanshinone production is largely *** we report single-base resolution DNA methylomes from roots and *** analysis revealed differential methylation patterns for CG,CHG,and CHH contexts and the association between DNA methylation and the expression of genes and small *** methylated genes always had higher expression levels and 24-nucleotide sRNAs could be key players in the RdDM pathway in *** methylation variation analysis showed that CHH methylation contributed mostly to the *** enrichment analysis showed that diterpenoid biosynthetic process was significantly enriched for genes with downstream overlapping with hypoCHHDMR in July_root when comparing with those in March_*** biosynthesis-related enzyme genes,such as DXS2,CMK,IDI1,HMGR2,DXR,MDS,CYP76AH1,2OGD25,and CYP71D373,were less CHH methylated in gene promoters or downstream regions in roots collected in July than those collected in ***,gene expression was up-regulated in *** roots collected in July compared with March and the treatment of DNA methylation inhibitor 5-azacytidine significantly promoted tanshinone *** suggests that DNA methylation plays a significant regulatory role in tanshinone biosynthesis in *** through changing the levels of CHH methylation in promoters or downstreams of key enzyme genes.

关键词： miltiorrhiza roots mechanism

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Short term effect of Salvia miltiorrhiza 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

AIM To study the short term effect of Danshen ( Salvia miltiorrhiza ) on acetic acid induced chronic gastric ulcer in rats and its long term effect in preventing recurrence. METHODS Rats with acetic acid induced gastric ulcer were treated with Danshen and cimetidine for 30 days. Traditional gastric mucosal auto radiography and 3H TdR incorporation into gastric mucosa in vitro were employed to study the effects of Danshen in rat acetic acid induced chronic gastric ulcer, including ulcer index (UI), ulcer inhibitory rate (IR) and label rate (LR). RESULTS On the day 5, 30 and 126 of ulcer making, the UI in the Danshen group was obviously lower than that in the cimetidine group and the control group (42 3±3 9, 3 6±1 2, 4 4±2 3; 49 1±3 6, 5 9±1 4, 9 2±1 3; 61 0±3 8, 8 9±2 5, 12 4±2 4, respectively, P <0 01), the IR (%) in the Danshen group was obviously higher than that in the cimetidine group (31, 59, 64 8; 19, 33, 26, respectively), and the LR in the Danshen group was obviously higher than that in the cimetidine group and the control group (10 0±0 5, 16 2±0 8, 15 0±0 6; 9 0±0 5, 13 9±0 6, 10 8±0 7; 6 5±0 7, 10 1±0 5, 8 0±0 7, respectively, P <0 01). There was no obvious difference in UI in the Danshen group on day 30 as compared with that on day 126. CONCLUSION Danshen is effective in promoting ulcer healing and preventing recurrence. The mechanism of action is to strengthen the gastric mucosal barrier and to promote the gastric mucosal cell proliferation along the edge of the ulcer.

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

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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

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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

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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

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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

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Protective effect of Salvia miltiorrhiza and Carthamus tinctorius extract against lipopolysaccharide-induced liver injury

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World Journal of Gastroenterology 2015年第30期21卷 9079-9092页

作者： Li-Na Gao Kuo Yan Yuan-Lu Cui Guan-Wei Fan Yue-Fei Wang Research Center of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine Tianjin State Key Laboratory of Modern Chinese Medicine Tianjin University of Traditional Chinese Medicine Research and Development Center of TCM Tianjin International Joint Academy of Biotechnology and Medicine

AIM:To investigate the hepatoprotective effects and mechanisms of an extract of Salvia miltiorrhiza and Carthamus tinctorius in ***:C57BL/6J mice were randomly assigned to five groups and intraperitoneally administered 0.9% saline,Salvia miltiorrhiza and Carthamus tinctorius extract [Danhong injection(DHI),0.75 and 3 g/kg mixed extract] or reduced glutathione for injection(RGI,300 mg/kg) for 30 min before exposure to lipopolysaccharide(LPS,16 mg/kg). After intraperitoneal LPS stimulation for 90 min or 6 h,the mice were sacrificed by ether anaesthesia,and serum and liver samples were collected. Histological analysis(H&E) and terminal deoxynucleotidyl transferase-mediated d UTP nick end-labelling(TUNEL) staining were performed. Alanine transferase(ALT),aspartate transaminase(AST),total bilirubin(TBil),glutathione-S-transferase(GST),malondialdehyde(MDA),tumour necrosis factor(TNF)-α,interleukin(IL)-6,and caspase-3 levels were measured. Bax,Bcl-2,P-IκBα,IκBα,P-NF-κB p65,and NF-κB p65 protein levels were determined by Western blot. TNF-α,IL-6,caspase-3,Bax and Bcl-2 m RNA expression was measured by real-time reverse transcription-polymerase chain reaction(RT-PCR).RESULTS:Hematoxylin-eosin staining and TUNEL results suggested that DHI(3 g/kg) treatment alleviated inflammatory and apoptotic(P < 0.01) injury in the liver of mice. DHI treatment dose-dependently blunted the abnormal changes in biochemical parameters such as ALT(72.53 ± 2.83 for 3 g/kg,P < 0.01),AST(76.97 ± 5.00 for 3 g/kg,P < 0.01),TBil(1.17 ± 0.10 for 3 g/kg,P < 0.01),MDA(0.81 ± 0.36 for 3 g/kg,P < 0.01),and GST(358.86 ± 12.09 for 3 g/kg,P < 0.01). Moreover,DHI(3 g/kg) remarkably decreased LPS-induced protein expression of TNF-α(340.55 ± 10.18 for 3 g/kg,P < 0.01),IL-6(261.34 ± 10.18 for 3 g/kg,P < 0.01),and enzyme activity of caspase-3(0.93 ± 0.029 for 3 g/kg,P < 0.01). The LPS-induced m RNA expression of TNF-α,IL-6 and caspase-3 was also decreased by DHI. Western blot analysis revealed that DHI an

关键词： Salvia miltiorrhiza Carthamus tinctorius Apoptosis Anti-inflammatory Antioxidant Acute liverinjury

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On Regional Division of Suitable Producing Areas of Yu Salvia miltiorrhiza

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Asian Agricultural Research 2012年第11期4卷 130-132页

作者： WEI Zhi-hua WANG Xin-min QIAO Qing-mei CHENG Mao-gao LIU Yong-lu XIE Cai-xiang CHEN Shi-lin Zhengzhou College of Animal Husbandry Engineering Institute of Medicinal Plant Development Chinese Academy of Medical SciencesChinese Peking Union Medical College

With the aid of the Traditional Chinese Medicine Geographic Information System(TCMGIS-I),on the basis of planting base of Yu Salvia miltiorrhiza in Fangcheng County of Henan Province,we selected key ecological factors such as the temperature,altitude,soil type,and precipitation that affect growth of Yu Salvia miltiorrhiza,and analyzed ecological suitability of Yu Salvia miltiorrhiza in China and in Henan *** show that Yu Salvia miltiorrhiza has large suitable area in China,up to 10 *** the similitude degree of 90% to 100%,its suitable distribution area can reach 309 205 km 2 *** the suitable areas,the distribution area is large in Sichuan,Shaanxi,Jiangsu,Hubei and Henan provinces,each of which up to 24 000 km *** the similitude degree of 80% to 90%,the suitable areas of Yu Salvia miltiorrhiza are mainly in Fangcheng,Xichuan,Dengzhou,Xinyang and Nanzhao counties,which are consistent with record of relevant data.

关键词： Yu Salvia miltiorrhiza TCMGI-I Suitability of prod

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Clinical study on Salvia miltiorrhiza + calcium dobesilate treatment of early retinopathy of type 2 diabetes mellitus

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Journal of Hainan Medical University 2019年第18期25卷 57-61页

作者： Du-Qin Wang Rui-Juan Guan Qian-Han Wang Ling Li Li Wan Traditional Chinese Medicine Hospital of Shijingshan District Beijing 100043China Teaching and Research Section of Traditional Chinese Medicine Department of Sports MedicineChengdu Sports UniversityChengduSichuan Province610075

Objective:To study the efficacy of Salvia miltiorrhiza+calcium dobesilate for early retinopathy of type 2 diabetes ***:The patients with non-proliferative diabetic retinopathy admitted to our hospital between August 2016 and February 2018 were chosen and randomly divided into the observation group receiving Salvia miltiorrhiza+calcium dobesilate treatment and the control group receiving calcium dobesilate *** treatment and 3 months after treatment,ophthalmologic examination was conducted to measure the hemangioma volume,macular thickness and blood spot area,and serum was collected to measure the contents of angiogenesis molecules,inflammation molecules and oxidative stress ***:The hemangioma volume,macular thickness and blood spot area as well as serum hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),erythropoietin(EPO),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),intercellular adhesion molecule-1(ICAM-1),malondialdehyde(MDA)and advanced oxidation protein product(AOPP)levels of both groups were significantly lower whereas serum pigment epithelium-derived factor(PEDF),heme oxygenase-1(HO-1),vitamin E(VitE)and total antioxidant capacity(TAC)levels were significantly higher after treatment,and the hemangioma volume,macular thickness and blood spot area as well as serum HIF-1α,VEGF,EPO,IL-1β,TNF-α,ICAM-1,MDA and AOPP levels of observation group after treatment were significantly lower than those of control group whereas serum PEDF,HO-1,VitE and TAC levels were significantly higher than those of control ***:Salvia miltiorrhiza+calcium dobesilate treatment of early retinopathy of type 2 diabetes mellitus is more effective than calcium dobesilate alone in improving the condition and inhibiting the angiogenesis,inflammation and oxidative stress.

关键词： Type 2 diabetes mellitus Diabetic retinopathy Salvia miltiorrhiza Angiogenesis Inflammation Oxidative stress

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Effects of complex salvia miltiorrhiza on blood coagulation, inflammation, oxidative stress and endothelial index in patients with acute pancreatitis

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Journal of Hainan Medical University 2018年第21期24卷 23-27页

作者： Ye Zhang Chun-Tao Li Lei Lu Department of Gastroenterology Shunyi District Hospital of BeijingBeijing 101300China

Objective: To investigate the effects of complex salvia miltiorrhiza on blood coagulation, inflammation, oxidative stress and endothelial index in patients with acute pancreatitis. Methods: A total of 122 patients with acute pancreatitis admitted to digestive system department in our hospital from April 2016 to November 2017 were randomly divided into control group (n=61) and observation group (n=61), the control group was treated with ulinastatin and the observation group was treated with complex salvia miltiorrhiza injection on the basis of the control group. The levels of coagulation, inflammation, oxidative stress and endothelial markers were compared between the two groups. Results: After treatment, the levels of APTT and PT in the two groups were significantly higher than those before treatment, while the levels of DD were significantly lower than those before treatment, and the levels of APTT and PT [(38.19±7.05) s,(17.60±3.68) s] in the observation group were significantly higher than those in the control group, while the levels of DD [(0.51±0.10) mg/L] in the observation group were significantly lower than those in the control group;the levels of CRP, PCT and TNF-α in the two groups were significantly lower than those before treatment, and the levels of CRP, PCT and TNF-α [(29.10±4.76) mg/L, (0.59±0.17) μg/L, (57.28±10.61) ng/L] in the observation group were significantly lower than those in the control group;the levels of SOD in the two groups were significantly higher than those before treatment, but MDA was significantly lower than that before treatment, and the level of SOD [(179.10±4.76) U/mL] in the observation group was significantly higher than that in the control group after treatment, while the level of MDA [(1.97±0.55) mmol/mL] in the observation group was significantly lower than that in the control group after treatment;the levels of NO in the two groups were significantly higher than those before treatment, while the levels of ET and vWF were

关键词： Complex salvia miltiorrhiza Acute pancreatitis Blood coagulation Inflammation Oxidative stress Endothelial

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