Characterization and function study of circadian rhythm gene CtPRR1 in Carthamus tinctorius L / 药学实践杂志

Objective To explore the effect of circadian rhythm genes on flavonoids biosynthesis in safflower and its molecular mechanism. Methods Based on the transcriptome and metabolomic database of safflower corolla, we screened the circadian rhythm genes that correlate with biosynthesis of flavonoids in safflower. qPCR was used to quantify the expressions of circadian rhythm genes in different flowering stages at different time points in a single day. LC-MS was performed to determine the accumulation of flavonoids. The correlation between them was analyzed as well. Yeast Two-Hybrid experiment was used to verify the interactive proteins of these genes. Results Seven circadian rhythm genes PRR1, PRR2, ELF3, FT, PHYB, GI and ZTL were obtained. PRR1 gene was positively correlated with flavonoids accumulation (r≥0.7). The full length of PRR1 is 3 201 bp, encoding 421 amino acids, which is highly homologous with rice OsPRR73 gene and named as CtPRR1 (GenBank accession number: MW492035). CtPRR1 was mainly expressed in flowers, and the expression level increased in the daytime and declined in the evening gradually. Correspondingly, the content of flavonoids showed an opposite variation. Both of them displayed a circadian rhythm with a negative correlation (r≥−0.7). In addition, 2 heat shock proteins along with 3 AP2 transcription factors interacting with CtPRR1 protein were obtained via Yeast Two-Hybrid experiment. Conclusion CtPRR1 negatively regulated the safflower flavonoids accumulation in a circadian rhythm way, which may be affected by these interacting proteins.

Study on the mechanism of the water extraction of Mongolian medicine Carthami flos in the treatment of chronic alcoholic liver injury based on metabonomics / 国际中医中药杂志

Objective:To explore the mechanism of the extraction of Carthami flos in the treatment of chronic alcoholic liver injury based on metabolomics. Methods:The rats were randomly divided into normal group, model group, positive control group and low, medium and high dose groups of the extraction of Carthami flos, with 10 rats in each group. In addition to the normal group, the other groups were gavaged with 8 ml/kg of 56° Niulanshan Baijiu to prepare the rat model with chronic alcoholic liver injury. After the successful modeling, the positive control group was gavaged with 0.36 mg/kg of Hugan tablet, and the low, medium and high dose groups were gavaged with 0.476 7, 1.430 1 and 4.290 3 g/kg of the extraction of Carthami flos respectively, once a day for 21 days. The contents of GPT, GOT, TG and ALP2 in serum were detected by automatic biochemical analyzer, and the effects of the extraction of Carthami flos on chronic alcoholic liver injury in rats were analyzed by Ultra High Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS), cluster analysis, Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). Results:The levels of GPT [(42.11±6.58)U/L, (42.38±6.58)U/L vs. (49.96±10.70)U/L] and GOT [(104.81±14.70)U/L, (102.91±23.65)U/L vs. (159.66±53.69)U/L] decreased ( P<0.05 or P<0.01), while the levels of TG [(0.85±0.29)U/L, (0.85±0.23)U/L vs.(0.62±0.21)U/L] and ALP2 [(104.53±13.53)U/L, (100.30±17.28)U/L vs.(77.13±12.54)U/L] increased ( P<0.05 or P<0.01); The results of cluster analysis, PCA and OPLS-DA showed that the model group and the high-dose group of the extraction of Carthami flos could be distinguished obviously. A total of 20 chemical markers were obtained in the serum of rats with chronic alcoholic liver injury treated with the extraction of Carthami flos. Among them, the extraction of Carthami flos can down regulate the level of serum linolenic acid triglyceride in rats with chronic alcoholic liver injury and up regulate triglyceride, palmitic acid, lysophosphatidylcholine, palmitoyl ethanolamide, epinephrine, sphingosine, lysophosphingomyelin α-Linolenic acid, docosahexaenoic acid and eicosapentaenoic acid are 10 endogenous metabolites. Conclusion:The treatment of chronic alcoholic liver injury with the extraction of Carthami flos may be related to the regulation of endogenous metabolites docosahexadilute acid, docosapentadilute acid α- Linolenic acid.

Mechanism of Carthami Flos and Lepidii Semen drug pair in inhibition of myocardial fibrosis by improving cardiac microenvironment based on network pharmacology and animal experiment / 中国中药杂志

Previously, Carthami Flos and Lepidii Semen(CF-LS) drug pair has been proved effective in inhibiting myocardial fibrosis(MF) by blunting the activity of cardiac fibroblasts. The present study explored the underlying mechanism of CF-LS in inhibiting MF by improving the cardiac microenvironment based on network pharmacology combined with experimental verification. Active compounds and potential targets of CF-LS were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the potential targets of MF were obtained from GeneCards, Online Mendelian Inheritance in Man(OMIM), and Pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGKB). The "active component-target-MF" network was constructed and analyzed by Cytoscape 3.8.1. The protein-protein interaction(PPI) network was constructed by STRING. The Gene Ontology(GO) biological process enrichment analysis was performed by CluoGO plug-in. Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analysis was performed by R 4.0.2 and Funrich. Subsequently, the inhibitory effect of CF-LS on MF was investigated based on angiotensin Ⅱ(Ang Ⅱ)-induced MF rats. RT-PCR and ELISA were used to verify the effect of CF-LS on the targets of signaling pathways related to vascular endothelial cells predicted by the network pharmacology. Thirty-one active components and 204 potential targets of CF-LS, 4 671 MF-related targets, and 174 common targets were obtained. The network analysis showed that the key targets of CF-LS against MF included RAC-alpha serine/threonine-protein kinase(AKT1), transcription factor AP-1(JUN), mitogen-activated protein kinase 1(MAPK1), cellular tumor antigen p53(TP53), transcription factor p65(RELA), and mitogen-activated protein kinase 8(MAPK8). Biological processes mainly involved regulation of blood vessel diameter, regulation of blood vessel endothelial cell migration, cell death in response to oxidative stress, etc. Advanced glycation end products(AGE)-receptor for advanced glycation end products(RAGE) signaling pathway, phosphoinositide 3-kinase(PI3 K)-serine/threonine protein kinase(AKT) signaling pathway, hypoxia-inducible factor-1(HIF-1) signaling pathway, integrin signaling pathway, transforming growth factor-β(TGF-β) signaling pathway, etc. were involved in signaling pathway enrichment. Literature retrieval confirmed that some of these signaling pathways were closely related to vascular endothelial cells, including AGE-RAGE, PI3 K-AKT, HIF-1α, p53, the transcription factor activator protein-1(AP-1), integrin, p38 MAPK, and TGF-β. Animal experiments showed that CF-LS inhibited MF induced by Ang Ⅱ in rats by suppressing the expression of RAGE, HIF-1α, integrin β6, and TGF-β1. The inhibitory effect of CF-LS on MF has the characteristics of multiple components, multiple targets, and multiple pathways. CF-LS can inhibit MF by regulating the activity of vascular endothelial cells in the cardiac microenvironment.

Compatibility of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos regulate insulin signaling pathway and alleviate insulin resistance in mice / 药学学报

Insulin resistance refers to the impaired ability of insulin to regulate glucose metabolism in peripheral organs, which is considered to be the etiology of type 2 diabetes. This study aims to explore the mechanism of improving insulin resistance by compatibility of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos (DH). Insulin resistance was conducted on C56BL/6J mice by treatment of high fat diet. The energy intake and body weight, plasma levels of triglycerides, total cholesterol, insulin and glucose, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT), as well as gene transcription and protein expression levels of insulin signaling pathway in liver, heart, kidney, and skeletal muscle of insulin resistance mice were evaluated. Animal experiments and welfare were performed in compliance with the guidelines of Animal Ethics Committee of Nanjing University of Chinese Medicine. The results showed that DH treatment significantly alleviated the excessive food intake and weight gain, and significantly decreased the levels of plasma triglycerides and total cholesterol, and constantly mitigated the hyperinsulinemia in insulin resistance mice. The results of OGTT and ITT suggested that DH treatment dramatically improved the response of insulin resistance mice to insulin stimulated glucose metabolism. Furthermore, the imbalance of metabolic arm and mitogenic arm of insulin signaling pathway in insulin resistance mice was normalized after DH treatment. DH treatment regulated insulin signaling pathway and improved the ability of glucose metabolism of insulin resistance mice.

Production and quality control of original herbal materials of Danhong Injection / 中国中药杂志

Cardiovascular and cerebrovascular diseases are the leading cause of death for residents in China. Danhong Injection(DHI) decoction piece is prepared from Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos, with the function of promoting the blood circulation, removing the blood stasis, relaxing the sinews and dredging the collaterals. In recent years, about 100 million bottles of DHI have been sold. Consequently, its safety and effectiveness are very important to a large number of patients. Raw materials are the source and foundation for production of traditional Chinese medicine injections. In this article, we reviewed the identification of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos, resource distribution, cultivation, quality control, and detection of xenobiotic pollutants, in order to guide the production of high-quality, stable, and pollution-free raw materials. This will be a benefit in ensuring the safety and effectiveness of DHI and reducing the incidence of adverse reactions from the raw materials. By comparing the similarities and differences between the quality standards of Salviae Miltiorrhizae Radix et Rhizoma, Carthami Flos and DHI, we provided some comments for improving the quality standards and post-marketing reevaluation of DHI, and provided some theoretical supports for the production of high-quality herbal raw materials.

Mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos Component Compatibility on Inflammatory Factor in Brain Tissue of Rats with Ischemic Stroke / 中国实验方剂学杂志

Objective:This study intends to study the regulatory effect and mechanism of the effective components of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos on inflammatory factors related to cerebral ischemia-reperfusion injury in rats through multiple levels of neuropathology， molecular neurobiology and functional behavior. Method:The 32 male rats were randomly divided into four groups： sham group， model group， Danhong components compatibility group（720 mg·kg-1）， nimodipine （0.5 mg·kg-1）groups，each group of eight male rats.Cerebral ischemia was established by middle cerebral artery occlusion （MCAO） approach. The treatment was performed immediately and at 6 hour after MCAO.Hematoxylin-eosin （HE）staining was used to check the changes of brain histopathology， immunohistochemistry and Real time polymerase chain reaction （Real-time PCR） were used to check the expression of IL-1β and Nrf2 in brain tissue，Western blot was used to detect the protein expression of Nrf2 in brain tissue. The aim is to investigate the treatment mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos components in a rat model of cerebral ischemic-reperfusion injury. Result:HE staining results showed， compared with sham group， the surviving neurons amount in the model group was significantly reduced（P<0.01），compared with the MCAO group，the number of surviving neurons in the brain tissue of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos component compatibility group and nimodipine group was significantly increased（P<0.05，P<0.01）.The results of immunohistochemistry and Real-time PCR showed that，compared with normal group，IL-1β and Nrf2 expression in model group were significantly increased （P<0.01），compared with MCAO group， the expression of IL-1β and Nrf2 in Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos component compatibility group and the nimodipine group was significantly decreased （P<0.05，P<0.01）. Western blot results showed that， compared with sham group， Nrf2 positive expression in model group was much more increased （P<0.01）， compared with MCAO group， the expression of Nrf2 in Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos component compatibility group and the nimodipine group was significantly decreased （P<0.01）. Conclusion:The combination of effective components of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos can significantly down-regulate the expression of IL-1β and Nrf2 proteins.The mechanism is to activate the protein expression of inflammatory pathways， reduce the apoptosis of nerve cells， and finally inhibit the inflammatory response in the process of ischemic stroke injury.

Nature-effect relationship research of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos based on nature combination / 中国中药杂志

Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos are commonly traditional Chinese medicines with invigorating blood circulation and eliminating blood stasis,but they are different in effects due to differences in five tastes and four properties. In this study,Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos are selected as research vectors to obtain the active ingredients and targets through TCMD,TCMSP database and Ch EMBL database. The protein interaction information of the target is used to obtain from STRING online database,then imported into Cytoscape software to plot the protein interaction network and perform GO enrichment analysis.The results show that the heart-liver protein interaction network,involving blood circulation and hepatic lipid metabolism,thereby exerting the effect of activating blood circulation. The cold-bitter protein interaction network involves the biological process of vasoconstriction,thereby exerting cooling blood and the efficacy of eliminating phlegm. The warm-pungent protein interaction network involves blood coagulation,lipid metabolism and other biological processes to play the role of phlegm pain. Through analysis,it is found that the relationship between pharmacological efficacy and medicinal properties has a certain degree of specificity,which facilitates the subsequent scientific and systematic study of medicinal properties on the basis of this study.

Study on preparation technology and physical fingerprint of Carthami Flos Granules based on quality by design / 中草药

Objective: To study the prescription and preparation technology of Carthami Flos Granules and evaluate its physical quality based on quality by design. Methods: Carthami Flos was used as a model drug. The evaluation indicators were retention rate of hydroxysafflor yellow A (HSYA) and total flavonoid, primary formation rate, bulk density, tap density, relative homogeneity index, Hausner ratio, angle of repose, loss on drying, and hygroscopicity. The single factor experiments and the Box-Behnken design response surface method were used to investigate the particle forming process parameters. The physical fingerprint of granules was constructed by seven indexes including bulk density, tap density, relative homogeneity index, Hausner ratio, angle of repose, loss on drying, and hygroscopicity. Results: The optimum conditions were as follows: the dosage ratio of drug to adjuvant was 10.8, the amount of wetting agent (95% ethanol) was 32%, and dried at 70 ℃ for 120 min. The similarity of the physical fingerprint of 10 batches of Carthami Flos Granules was higher than 0.99. Conclusion: The prescription and preparation technology of Carthami Flos Granules and the physical quality were scientific and reasonable, which can provide ideas and methods for the research and development of Chinese materia medica.

Network pharmacology-based study on mechanisms of Danhong Injection in treatment of aspirin resistance / 中国中药杂志

This paper aims to discuss the potential targets,pathways and possible mechanisms of Danhong Injection in treatment of aspirin resistance by using network pharmacology concept and network analysis technique. Active ingredients and potential targets of Danhong Injection were collected from TCMSP database and the ingredients were further screened based on their topological characteristics. The active ingredients with nodal degree of freedom≥9 were selected as the main active ingredients. Targets related to aspirin resistance were collected from Genecards database. Drug-active ingredient-target-disease network was constructed by using Cytoscape3. 7. 0,and Funrich 3. 1. 3 software was used for gene enrichment analysis. Sixty main active ingredients were screened out from 110 active ingredients of Danhong Injection,including 51 ingredients in Salviae Miltiorrhizae Radix et Rhizoma and 11 ingredients in Carthami Flos,2 of which were both in Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos. In addition,159 potential targets were collected. The results of gene enrichment analysis showed that Danhong Injection could improve aspirin resistance mainly through21 pathways involving coagulation process,inflammatory response and metabolism. This study revealed the effects of Danhong Injection for improving aspirin resistance in multi-component,multi-target and multi-pathway means mainly through regulation in coagulation process,inflammatory response and metabolism,providing more abundant information and basis for subsequent research and experimental work.

Effect of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos before and after compatibility on activities of CYP1A2, CYP2E1, and CYP3A4 from rat liver microsomes / 药物评价研究

Objective To study the influence of Salviae Miltiorrhizae Radix et Rhizome (SMR) and Carthami Flos (CF) before and after compatibility on activitis of cytochrome P 1A2 (CYP1A2),cytochrome P2E1 (CYP2E1),and cytochrome P3A4 (CYP3A4) from rat liver microsomes.Methods Using caffeine,chlorzoxazone,and midazolam as the probe drugs ofCYP1A2,CYP2E1,and CYP3A4,the SD rats were randomized divided into four groups:control group,SMR (1.2 g crude drug/kg) group,CF (0.4 g crude drug/kg) group,and SMR (1.2 g crude drug/kg) + CF (0.4 g crude drug/kg) group.According to the above dose,rats were ig given drugs for 7 d.Rats were injected with caffeine,chlorzoxazone,and midazolam solution in tail vein 30 rain after the last administration,and the blood was collected at different time points.Metronidazole as internal standard,method has been established to determine the levels of caffeine,chlorzoxazone,and midazolam to evaluate the activities of CYP1A2,CYP2E1,and CYP3A4 by HPLC.Results Compared with control group,SMR increased the clearance rates (CL) of caffeine,chlorzoxazone,and midazolam,reduced the AUC,and t1/2 was also show a decreasing trend,but the difference was not significant.In CF group,CL of caffeine and chlorzoxazone was decreased,but the difference is not significant.CL of midazolam significantly decreased (P ＜ 0.01).AUC of chlorzoxazone increased,but the difference was not significant.AUC of caffeine and midazolam increased significantly (P ＜ 0.05 and 0.01).In SMR + CF group,the CL of caffeine and chlorzoxazone decreased significantly (P ＜ 0.05),the AUC of caffeine and chlorzoxazone increased significantly (P ＜ 0.05),and t1/2 also showed a decreasing trend,but the difference is not significant.Conclusion Compatibility of SMR and CF has an inhibitive effect on CYP1A2 and CYP2E1 in rats,and it could be one of the mechanisms ofinteractive synergy.

Effect of promoting blood circulation of herb pair containing Angelicae Sinensis Radix and Carthami Flos / 中草药

Objective: To demonstrate the range, properties and extent of the interaction for activating blood effects in herb pair containing Angelicae Sinensis Radix and Carthami Flos (ASR-RC) by response surface method. Methods: Based on the acute blood stasis rats model, the hemorheological indexes of ASR-RC with different proportions (1:0, 4:1, 2:1, 3:2, 1:1, 2:3, 1:2, 1:4, 0:1) and different concentration were observed. Then all data were integrated to the total activating blood circulation effect value by comprehensive index method. The interaction was analyzed by response surface method. Model parameters were estimated with nonlinear regression. The three-dimensional response surfaces were constructed with Matlab software. Results The proportion from 0.8:1 to 1.1:1 of ASR-RC had synergetic effects, and when the dose of Angelicae Sinensis Radix ranged from 0 g to 5 g, and Carthami Flos from 8 g to 11 g, the herb pair also had synergetic effects (with the value between -0.2 and -0.8). In addition, when the dose of Angelicae Sinensis Radix ranged from 0 g to 0.2 g, and Carthami Flos ranged from 0.2 g to 1 g, the herb pair had antagonism action (with the value of 0.2). Conclusion The research results could provide scientific evidence for clinical application of ASR-RC. And quantitative analysis on drug interactions of herb pair by response surface method could also provide references for relevant studies.

Chemical interaction analysis on compatibility of Danshen-Honghua pair by using HPLC-PDA / 中草药

Objective: A novel and generally applicable approach was established for the interaction analysis on compatibility of Danshen-Honghua (Salviae Miltiorrhizae Radix and Carthami Flos) pair with different preparations and proportions when decocting together by using HPLC-PDA and fuzzy chemical identification strategy with poly-proportion design. Methods: A simple project was initially developed for the rapid identification and classification of four types of components in Danshen-Honghua based on the establishment of relevant component data base, recognition of the reference compound peaks, selection of the characteristics of ultraviolet spectrum, and formation of group networks. In this study, the accurate structures of the chemical components did not need to be determined, and only the constituents attributed to different groups were further considered for quantitative analysis. Results: A total of 47, 57, and 43 constituents from different preparations of Danshen-Honghua were classified into four kinds of chemical groups, and they were quantitatively analyzed furtherly according to semi-symmetric proportion design. The results showed that the preparation of methanol-water could significantly promote the dissolution of most salvianolic acids, chalcones, and flavonoids, while the contents of tanshinones in methanol were higher than others. The relative dissolution rate range of total optimization for the four types of components were from 5:1 to 5:2, and the highest proportion of the total relative dissolution were all 5:2. Conclusion: The most reasonable range may appear 5:1-5:2 for water preparation and be consistent with clinical ratio, which provides the reference for clinical application of Danshen-Honghua pair, and for modern research approach of herb pairs.

Data mining analysis of regularity of formulas containing Salviae Miltiorrhizae Radix et Rhizoma-Carthami Flos medicin pair in Dictionary of Chinese Medicine Prescription / 中国中药杂志

In this study, formulas containing Salviae Miltiorrhizae Radix et Rhizoma-Carthami Flos in the database of Dictionary of Chinese Medicine Prescription (DCMP) were extracted by using traditional Chinese medicine inheritance support system (TCMISS). The drugs pairs and formula composition rules were analyzed with data mining methods, such as association rules, improved mutual information method and complex system entropy clustering. Totally 39 formulas were included in this study and involved 280 Chinese medicines. The top 5 Chinese medicines most frequently used were Danggui (Angelica sinensis), Chuanxiong (Ligusticum chuanxiong), Xiangfu (Cyperi Rhizoma), Baishao(Radix Paeoniae Alba), Taoren(Prunus persica) and Shengdihuang (Radix Rehmanniae Recens). Six core medicinal pairs were obtained through clustering analysis, namely Danshen (Salviae Miltiorrhizae Radix et Rhizoma)-Xiangfu (Cyperi Rhizoma)-Honghua (Carthami Flos), Danshen (Salviae Miltiorrhizae Radix et Rhizoma)-Baishao (Radix Paeoniae Alba)-Honghua (Carthami Flos), Danshen (Salviae Miltiorrhizae Radix et Rhizoma)-Danggui (A. sinensis)-Xiagnfu (Cyperi Rhizoma)-Honghua (Carthami Flos), Danshen (Salviae Miltiorrhizae Radix et Rhizoma)-Danggui (A. sinensis)-Baishao (Radix Paeoniae Alba)-Honghua (Carthami Flos), Honghua (Carthami Flos)-Danshen (Salviae Miltiorrhizae Radix et Rhizoma)-Baishao (Radix Paeoniae Alba)-Danggui (A. sinensis), Danshen (Salviae Miltiorrhizae Radix et Rhizoma)-Baishao (Radix Paeoniae Alba)-Honghua (Carthami Flos)-Danggui (A. sinensis). The support degree was set at 11 (38.46%), with a confidence coefficient of 80%, and then 38 associated pairs were screened. These results suggested that Salviae Miltiorrhizae Radix et Rhizoma, Carthami Flos is often combined with herbs for activating blood and promoting circulation of qi to treat gynecopathy, stasis blood pain syndrome, stroke and other syndromes.

Carthami flos: a review of its ethnopharmacology, pharmacology and clinical applications

ABSTRACTCarthami flos, the dried floret of Carthamus tinctorius L., Asteraceae (safflower), has been widely used in traditional Chinese medicine to treat a broad range of ailments, such as coronary heart disease, angina pectoris, gynecologic disease, stroke, and hypertension. However, although several studies on Carthami flos have been done consecutively, the results are usually scattered across various documents. This review aims to provide up-to-date information on the traditional uses, pharmacology, clinical applications, and toxicology of Carthami flos in China and thereby to provide a basis for further investigation of its use to treat dissimilar diseases. Various ethnomedical uses of Carthami flos have been documented in many ancient Chinese books. Crude extracts and isolated compounds from Carthami flos show a broad range of pharmacological properties, such as protective effects on brain tissue, on osteoblasts, and in myocardial ischemia, as well as anti-inflammatory, antithrombotic, antitumor, and antidiabetic activities. To date, safflower and safflor yellow injections have been used to treat coronary heart disease, chronic pulmonary heart disease, cerebrovascular diseases, orthopedic diseases, and diabetes mellitus. Regarding the toxicology of Carthami flos, among the side effects that have been observed are allergic reaction, spermatogenetic failure, fatty liver, and nephrotoxicity.

Determination Method Optimization of Chromium Element in Carthami Flos by Orthogonal Design / 中国药师

Objective:To explore the optimum digestion condition by orthogonal design, and determine the chromium content in Carthami flos by atomic absorption spectrometry ( AAS) to provide the experimental basis for the establishment of trace element limit standard. Methods:The conditions of microwave digestion were optimized using L9 (34 ) orthogonal experimental design, and chromi-um was determined by graphite furnace ( GF)-AAS. Results:The optimal digestion conditions were as follows:nitric acid-hydrochloric acid system was with the ratio of 6∶2, the highest resolution temperature was 185 ℃ with the duration of 25 minutes. The chromium content in 15 batches of Carthami flos was with significant differences. The chromium content in 15 batches of Carthami flos was detec-ted withhin the range of 0. 53-88. 15 mg·kg-1, the average recovery was 97. 1% and RSD was 2. 2%(n=9). Conclusion: The method is simple, accurate and reproducible, and can be used in the quality control of chromium in Carthami flos.

Effect of extract from Trichosathis Fructus, Carthami Flos, Chuanxiong Rhizoma, and Chrysanthemi Flos on oxidative stress-induced gut immunity in Drosophila melanogaster / 中草药

Objective: To study the effect of the extract from Chinese materia medica (CMM) on oxidative stress-induced gut immunity of Drosophila melanogaster. Methods: D. melanogaster was treated by Paraquat and H2O2 with or without CMM, and the effects of 50 kinds of CMM on the survival rate of D. melanogaster in response to oxidative stress were recorded. And the antioxidant effects of CMM on lifespan and the number of ISC and enteroblast (EB) in intestinal epithelium cells were analyzed. Results: The extracts from Trichosanthes kirilowii (Trichosathis Fructus), Carthamus tinctorius (Carthami Flos), Ligusticum chuanxiong (Chuanxiong Rhizoma), and Chrysanthemum monfolium (Chrysanthemi Flos) could significantly improve the survival rate of Paraquat and H2O2-induced D. melanogaster, increase the lifespan of D. melanogaster, and regulate Paraquat-induced and age-related changes in the number of ISC and EB. Conclusion: The extracts from T. kirilowii, C. tinctorius, L. chuanxiong, and C. monfolium could significantly improve the oxidative stress-induced gut immunity of D. melanogaster.

Effects of Sappan lignum on pharmacokinetics of hydroxysafflor yellow a from Carthami flos in rats with cold coagulation and blood stasis / 第二军医大学学报

Objective To develop a reversed phase high performance liquid Chromatographie (RP-HPLC) analysis system for hydroxysafflor yellow A (HSYA) in rat model of cold coagulation and blood stasis (CCBS), and to investigate the influence of Sappan lignum on the pharmacokinetics of HSYA in CCBS rats. Methods Rat CCBS models were randomly divided into two groups with each containing 6 animals. Rats were orally given Carthami flos extract or Carthami flos extract combined with Sappan lignum (The dosage: 20. 0 g/kg crud drug of Carthami flos). Plasma samples were collected in heparinized tubes from the oculi chorioideae vein at 5, 10, 20, 30, 45, 60, 90, 120, 150, 210, and 270 min after drug administration; and the plasma proteins were precipitated with 20% trichloroacetic acid aqueous solution. Plasma concentrations of HSYA were detected by RP-HPLC at different time points after drug administration. The data were processed by DAS 2. 0 software to calculate the pharmacokinetic parameters. Results Compared with the Carthami flos group, the pharmacokinetic parameters V1/F and CL/ Fof HSYA in the Carthami flos combined with Sappan lignum group were significantly decreased (P<0. 01), and the AUCo-t, Cmax, and t1/2α of HSYA were significantly increased (P<0. 01). Conclusion Sappan lignum can promote the absorption of HSYA in rat model of CCBS and reduce the distribution of HSYA, thus exercise an efficacy-enhancing effect.

Spectrum-activity relationship of Angelicae Sinensis Radix-Chuanxiong Rhizoma supercritical fluid extraction with Carthami Flos against myocardial ischemia / 中草药

Objective: To study the spectrum-activity relationships between the anti-myocardial ischaemia activity and the HPLC fingerprints of the formula, consisting of Angelicae Sinensis Radix-Chuanxiong Rhizoma supercritical fluid extraction (AC-SFE) and Carthami Flos (CF) solvent-extracted extracts. Methods: The rat model of acute myocardial ischemia was established by applying left anterior descending coronary ligation, and bivariate correlation analysis (BCA) and multivariate regression analysis (MRA) were used to investigate the spectrum-activity relationship between fingerprints and anti-myocardial ischaemia activity. LC-MS was used for peak assignment. Results: Eight peaks of AC-SFE were negatively correlated with the infarct size ratio (ISR) and the serum lactate dehydrogenase (LDH), and four of them were significantly correlated. Peak 8 (quercetin-3-O-β-D-galactose glycosides-4'-O-β-D-pyranglucoside) from CF was positively correlated with the efficacy. Study by regression analysis showed four peaks were in regression equations. LC-MS showed 16 peaks, among which 12 were correlated peaks. Conclusion: Ferulic acid (peak 13), senkyunolide H (peak 15), 3-hydroxy butylphthalide (peak 16), senkyunolide A (peak 18), 3-butylphthalide (peak 19), ligustilide (peak 20), dibutyl phthalide (peak 21), and phthalide (peak 17) of AC-SFE and peak 1 (4-methoxy-6-[3, 4, 5-trihydroxy-6-[[3, 4, 5-trihydroxy-6 (hydroxymethyl) tetra-hydropyran-2-yl]oxymethyl] tetrahydropyran-2-yl]oxy-cyclohexane-1, 2, 3, 5-tetrol) and peak 2 (3-{[6-O-(D-Galactopyranosyl)-β-D- galacto-pyrano-syl]oxy}-1,2-propanediyl diacetate) of CF might be the material foundation for the anti-myocardial ischaemia activity. Peak 8 might not be able to relieve myocardial ischaemia.

Study on distribution and correlation of fifteen inorganic elements in ten kinds of Chinese medicinal materials / 中国药学杂志

OBJECTIVE: To study the distribution and correlation of 15 inorganic elements, which are Al, As, Ba, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Se, Sn, Pb and Zn, in 10 kinds of Chinese medicinal materials(Lonicerae Japonicae Flos, Carthami Flos, Schisandrae Chinensis Fructus, Crataegi Fructus,Moutan Cortex, Phellodendri Chinensis Cortex, Centellae Herba, Menthae Haplocalycis Herba, Bombyx Batryticatus, Pheretima). METHODS: The levels of 15 inorganic elements in 10 kinds of Chinese Medicinal Materials were determined by ICP-MS and ICP-OES with microwave digestion for sample preparation, and the results were analyzed with SPSS15.0. RESULTS: Some residues of heavy metals in the Chinese Medicinal Materials overstepped the limits. The levels of almost all kinds of inorganic elements in Pheretima and Centellae Herba were relatively higher than others. The levels of Al and Ba in several batches were evidently and singularly higher than others in the same kind of Chinese Medicinal Materials. Besides Ba, Hg and Pb, the levels of other 12 inorganic elemens showed extremely significant positive correlation. Cu/Zn radio in those Chinese Medicinal Materials with cardiovascular effects were higher than others. CONCLUSION: To ensure the quality and safety, it is necessary to strengthen the supervision and control of the levels of some inorganic elements in Chinese medicinal materials. Copyright 2012 by the Chinese Pharmaceutical Association.

Correlation of combinations between Angelicae Sinensis Radix and Carthami Flos / 中草药

Objective: To study the correlation of combinations in different proportions of Angelicae Sinensis Radix and Carthami Flos and explore the regularity in proportion of the two drugs compatibility. Methods: Data mining technology was applied to screening the proportions of Angelicae Sinensis Radix and Carthami Flos. The changes of the contents of ferulic acid, hydroxysafflor yellow A, chlorogenic acid, and coumaric acid in the single and mixed decoction of Angelicae Sinensis Radix and Carthami Flos were determined by HPLC. The experiments of thrombin time and scavenging DPPH were carried out to evaluate the pharmacological activities of compatibility between Angelicae Sinensis Radix and Carthami Flos. Results: The top 10 proportions of Angelicae Sinensis Radix and Carthami Flos were screening. The contents of ferulic acid, hydroxysafflor yellow A, chlorogenic acid, and coumaric acid were higher than the single decoction of Angelicae Sinensis Radix and Carthami Flos. Thrombin time was prolonged and the activity of scavenging DPPH was enhanced compared to the same drug dosage of the single decoction of Angelicae Sinensis Radix and Carthami Flos. Conclusion: Mixed decoction of Angelicae Sinensis Radix and Carthami Flos is rational and good for the stripping of aromatic acids from the drugs, which has some correlation with the change of activities of the compatibility between Angelicae Sinensis Radix and Carthami Flos.