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Renal fibrosis， the final pathological outcome of end-stage chronic kidney diseases， is associated with inflammation， oxidative stress， epithelial-mesenchymal transdifferentiation （EMT）， and extracellular matrix deposition. It belongs to the categories of edema， ischuria， anuria and vomiting， and consumptive disease in traditional Chinese medicine （TCM）， with the key pathogenesis of Qi deficiency and blood stasis and the primary treatment principle of replenishing Qi and activating blood. Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma mainly contains astragalosides， polysaccharides， calycosin， salvianolic acid， and tanshinone， with the effect of tonifying Qi and activating blood. Studies have shown that this herb pair and its active components can delay the progress of renal fibrosis by regulating multiple signaling pathways. With consideration to the pathogenesis of Qi deficiency and blood stasis， this article reviews the research progress in the mitigation of renal fibrosis by Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma from the aspects of protecting glomerular filtration barrier， inhibiting EMT and mesangial cell proliferation， improving renal hemodynamics， and protecting renal function. Furthermore， the mechanisms were summarized. Specifically， Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma and its effective components can improve mitochondrial function and fatty acid metabolism， alleviate endoplasmic reticulum stress and autophagy disorders， and inhibit immune inflammation and oxidative stress by regulating nuclear factor E2-related factor 2 （Nrf2）/PTEN-induced kinase 1 （Pink1）， Nrf2/antioxidant response element （ARE）， tumor necrosis factor-α （TNF-α）/nuclear transcription factor-κB （NF-κB）， miR-21/Smad7/transforming growth factor beta （TGF-β）， Wnt/β-catenin， long non-coding RNA-taurine up-regulated gene 1 （lncRNA-TUG1）/tumor necrosis factor receptor-associated factor 5 （TRAF5）， Ras-related C3 botulinum toxin substrate 1 （Rac1）/cell division cycle protein 42 （CDC42）， Ras homolog （Rho）/Rho-associated coiled-coil containing protein kinase （ROCK）， phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， peroxisome proliferator-activated receptor α （PPARα）/peroxisome proliferator-activated receptor γ coactivator l alpha （PGC-1α）， and p38 mitogen-activated protein kinase （p38 MAPK）. This review aims to provide references for the relevant research， give play to the role of Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma， and provide guidance for the clinical treatment of renal fibrosis.
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Hypertensive renal damage is one of the most serious complications of hypertension, and it is also the main cause of end-stage renal disease. Renal damage can further promote the rise of blood pressure and difficult to control, forming a vicious circle. Traditional Chinese medicine (TCM) considers that deficiency of the original and excess of the standard is its basic pathogenesis, and insufficient kidney-Qi and blood stasis are one of the most common syndromes of hypertensive kidney damage. Astragali Radix membranaceus is praised as the most important medicine for invigorating Qi, and Salviae Miltiorrhizae Radix is likened to "four things with the same function". Based on the theory of invigorating Qi and activating blood circulation, the effective ingredients of Astragali Radix membranaceus-Salviae Miltiorrhizae Radix are mainly astragaloside, Astragali Radix polysaccharide, mulberry isoflavone, salvianolic acid and tanshinone. Many studies have shown that in the process of hypertensive kidney damage, Astragali Radix membranaceu Its active ingredients, whether effective monomers, monomer compatibility or direct compatibility of drug pairs, can regulate blood pressure, reduce urinary protein, protect renal tubules, protect glomerular filtration barrier, improve renal hemodynamics and protect renal function by regulating multiple signal transduction pathways related to hypertensive renal damage. Lowering blood pressure and protecting renal function are two pronged functions. Based on the theory of Invigorating Qi and activating blood circulation, this paper reviews the research progress of Astragali Radix-Salviae Miltiorrhizae Radix in the treatment of hypertensive renal damage, with a view to providing scientific basis for the further study and clinical application of Radix astragali-Salviae Miltiorrhizae Radix in hypertensive renal damage.
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To characterize and identify multiple constituents in Danhong injection (DHI), a fast ultra-high performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-QTOF/MS) method was established and validated in the present study. A total of 63 compounds, including 33 phenolic acids, 2 C-glycosyl quinochalcones, 6 flavonoid O-glycosides, 4 iridoid glycosides, 6 organic acids, 5 amino acids, and 3 nucleosides, were identified or tentatively characterized. In conclusion, the UHPLC-ESI-QTOF/MS method is useful and efficient for in-depth structural elucidation of chemical compounds in complex matrices of herbal medicines such as DHI.
Subject(s)
Chromatography, High Pressure Liquid , Methods , Drugs, Chinese Herbal , Chemistry , Spectrometry, Mass, Electrospray Ionization , Methods , Tandem Mass Spectrometry , MethodsABSTRACT
Objective The existing Quality Standards for Qianliean Capsules lack the quantitation control item and therefore cannot completely reflect the quality of the preparation .This study aimed to establish the methods for qualitation and quantitation of Qianliean Capsules . Methods Thin-layer chromatography ( TLC) was used for the qualitative identification of Radix Salviae miltior-rhizae, Rhizoma curcumae, and Glycyrrhiza uralensis in Qianliean Capsules .The content of hesperidin was determined by high-per-formance liquid chromatography ( HPLC) , and the method of determination was systematically evaluated . Results TLC spots were clear with a strong specificity .The content of hesperidin showed a good linear relationship within the range of 11 .56-310 .00μg/mL (r=0.999 5), with a mean recovery rate of 99.55% and relative standard deviation of 1.93%. Conclusion The qualitation and quantitation methods we established were simple , accurate and reliable , with a good reproducibility , and can be used for the quality control of Qianliean Capsules .
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Objective To compare the pharmacokinetics difference of methotrexate ( MTX) alone or MTX combined with the decoction of Radix Salviae Miltiorrhizae ( RSM) in rats, and to investigate the possible impact of RSM on the efficacy and pharmacokinetics of MTX after oral administration. Methods Sprague-Dawley rats were given MTX (7 mg/kg) alone or MTX together with RSM (3.085 g/kg) respectively. At different time points, blood was sampled from orbital venous plexus and then was precipitated by perchloric acid. The serum concentration of MTX was determined by using high performance liquid chromatography ( HPLC) method. Chromatographic separation was achieved on a reversed-phase Diamonsil C18 (2) column with the mobile phase of methanol-formic acid water solution (formic acid in volume fraction of 0.1%) in gradient elution. The column temperature was 27 ℃, flow rate was 1 mL/min, detection wavelength was 302 nm, and the injection volume was 10 μL. The results were analyzed by pharmacokinetic software DAS ( 2.1.1) by non-compartment model. Results The linearity of the calibration curve for MTX was good in the range of 0.097 6 ~ 12.5 mg/L, the detection limit was 0.097 6 mg/L and the recovery was in the range of 77.5% ~ 86.6%. Compared with MTX group, the peak-arriving time of MTX-RSM group was advanced, and the clearance of MTX was delayed. Area under concentration-time curve at 0-t (AUC(0-t)) was increased by 0.609 times, and AUC(0-∞) was increased by 0.786 times. Conclusion The decoction of RSM exerts an effect on promoting the absorption of MTX, delaying the clearance of MTX and enhancing the bioavailability of MTX in vivo.
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Objective To study the effect of Radix Salviae Miltiorrhizae (RSM), a kind of Chinese Traditional Medicine which can dissolve stasis by activating blood circulation, on proliferation, invasion, adhesion, migration and metastasis of B16-BL6 metastatic mouse melanoma cells and discuss its functional mechanism. Methods The proliferation, adhesion, invasion and migration capacity of B16-BL6 metastatic cells was evaluated by MTT assay, adhesion assay and reconstituted basement membrane invasion and migration assay in vitro respectively. Mouse spontaneous melanoma model was used to study the effect of RSM on metastasis in vivo. Results The extract of RSM bidirectionally adjusted the multiplication of B16-BL6 cells, promoted prominently the adhesion of B16-BL6 to Laminin, inhibited significantly B16-BL6 invading reconstituted basement membrane and the migration of B16-BL6. In the mouse spontaneous melanoma model, it suppressed significantly the volume of lung metastatic nodes but had little effect on the number of lung metastatic nodes. Conclusion The extract of RSM can alleviate the degree of the metastasis of B16-BL6 metastatic mouse melanoma cells, which may be related with inhibiting the B16-BL6 cells invading the extracellular matrix and reducing the migration of B16-BL6 cells.
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@# ObjectiveTo observe the effect of monosialo gangliosides-1 (GM-1) and Radix salviae miltiorrhizae (RSM) on neonatal hyposemic ischemic encephalopathy (HIE).Methods62 cases of HIE were randomly divided into treatment group and control group, and both groups received conventional therapy. Injection of RSM and GM-1 were added into the treatment group in 7～10 days therapy. ResultsHigh curative effect, average curative effect and total curative effect in the treatment group of 31 cases were 80.6%, 16.1% and 96.8%, while that in control group of 31 cases were 32.3%, 51.6% and 83.9% respectively. There was significant difference in the high curative effect and total effect between the two groups (P<0.05). ConclusionThe treatment combined with RSM and GM-1 can enhance the curative effect on HIE without any side effect.
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OBJECTIVE: To observe the effects of combined application of Radix Salviae Miltiorrhizae injection and dopamine injection on peritoneal dialysis patients.METHODS: By self-control method,the peritoneal dialysis solution of 22 patients with ambulant continued peritoneal dialysis was added with 20 mg dopamine injection and 12 mL Radix Salviae Miltiorrhizae injection for dialysis of 14 days.The D/P values of urea nitrogen(UN) and creatinine(Cr),week's peritoneal UN clearance index(KT/V),the clearance rate of Cr(Ccr),week's total KT/V,Ccr,reabsorption rate of glucose and the net amount of 24 hours' ultrafiltration were recorded before and after medication.RESULTS: The addition of dopamine injection and Radix Salviae Miltiorrhizae injection to the peritoneal dialysis solution resulted in significant higher values in week's peritoneal KT/V,Ccr and week's total KT/V,Ccr and the net amount of 24 hours' ultrafiltration as compared with before medication(P
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Objective To establish an ultra-high performance liquid chromatographic fingerprinting analysis method for the hydrophilic component of salvianolic acids and the lipophilic component of tanshinones in Radix Salviae Miltiorrhizae(RSM),and to supply a rapid and scientific method for quality control of RSM.Methods The chromatographic conditions were as follows: Acquity C18 BEH(2.1mm?100 mm,1.7 ?m)chromatographic column at 30℃,gradient elution with acetonitrile(A) and 0.4% formic acid(B)(90%~50% A for 0~10 min,75% A for 15 min),the flow rate being 0.5 mL?min-1 and UV detection wavelength set at 280nm.Results The chromatograms of the hydrophilic component and the lipophilic component were obtained within 15min,peak volume being 85.There were 20 peaks separated completely and identified by using HPLC-diode array detection-electrospray ionization-mass spectrometry.Conclusion The developed method is proved practicable,rapid and reliable for quality control of RSM and its preparations.
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Objective To investigate whether pharmacological serum from the rats taking radix salviae miltiorrhizae (RSM) can inhibit increase of intracellular free calcium level in hepatic stellate cells (HSCs). Methods A total of 32 healthy SD rats were divided into 4 groups. Two groups were modeled into hepatic fibrosis by 40% CCl 4 injection subcutaneously for 9 weeks and RSM were filled into the stomachs of one group (group A) but the same volume of saline into the other group (group B) twice a day for 6 d. Another two groups were only filled with RSM (group C) and saline (group D) for 6 d without modeling into hepatic fibrosis. The pharmacological serum was drawn from the inferior vena cava at 2 h after the last time of RSM or saline and used to culture HSCs at the concentration of 10% for 24 h. After HSCs were loaded with Fluo-3/AM, the effects of RSM on [Ca 2+ ] i with laser scanning confocal microscopy were examined before and after angiotensin Ⅱ treatment. Results In the activated HSCs of groups A and C, [Ca 2+ ] i decreased significantly as compared with groups B and D (P
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OBJECTIVE: To study the preparation technique of tanshinone dispersible tablets.METHODS: Taking the disintegration time - limit, in vitro dissolubility and suspensibility as indices, the formula of tanshinone dispersible tablets was screened by orthogonal design.RESULTS The dispersible tablets could completely disintegrate within 30 seconds and pass through 710m seive mesh, which all conformed to the requiremtes of BP(1993) .The in vitro dissolubility of this product was superior to that of ordinary tablets obviously .CONCLUSION: The preparation technique of tanshinone dispersible tablets is mature and the quality is reliable.
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Objective To explore the optimal process conditions for cold-soaking extraction of fat-soluble components in Radix Salviae Miltiorrhizae.Methods Tanshione Ⅱwas determined by HPLC.The effect of different concentrations of ethanol and comminution on the extraction rate of tanshione Ⅱwas observed,and the process conditions were optimized by orthogonal test.Results The optimal process conditions for obtaining higher extraction rate of tanshione Ⅱwere as follows: the medicinal material was extracted by cold-soak extraction with 95% ethanol for two times(3 hours for each time),and the volume of ethanol was as much as 8 times of the medicinal material.Conclusion The extraction process is simple,stable and efficient for Radix Salviae Miltiorrhizae.
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Object To determine the rationality of prescription of XIAOYU TABLETS. (Tablet for the elimination of blood stasis). Methods The effects of XIAOYU TABLETS and its individual constituents on endothelin 1 and nitric oxide in atherosclerotic rabbits were observed and compared. Results XIAOYU TABLETS showed stronger actions than its individual constituents (extract of Radix Salviae Miltiorrhizae or Fructus Crataegi) in decreasing the contents of endothelin 1 in plasma and atherosclerotic vessel wall and increasing the contents of nitric oxide in serum and atherosclerotic vessel wall. Conclusion The combine use of Radix Salviae Miltiorrhizae and Fructus Crataegi extracts showed an obvious synergistic effect on reduction of endothelin 1 and elevation of nitric oxide in atherosclerotic rabbits.
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Object To investigate the chromatographic fingerprints of Radix Salviae Miltiorrhizae (RSM), its intermediate and INJECTION by HPLC-UV-MS. Methods Separation was performed on an Alltima C 18 analytical column with the mobile phase consisting of methanol-water-acetic acid as gradient eluent at the flow rate of 1 mL/min. The UV detection was set at 281 nm and TIC was recorded by an electrospray ionization mass spectrometer in negative ion mode. Results The HPLC-UV and HPLC-MS fingerprints of RSM, its intermediate and INJECTION were obtained with perfect isolation. Conclusion The fingerprints could be used for the control of RSM, its intermediate and INJECTION.
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Object To research on genetic relationship among the main populations of Salvia miltiorrhiza Bge. and the genuineness of the herb. Methods From main distributed places, 44 samples (including nine populations) were analyzed by RAPD. The data of amplified bands were analyzed by the software NTSYS-pc and AMOVA. Results (1) From more than 100 primers, 11 primers producing polymorphism and reproduceable bands were selected, 129 bands were amplified. (2) The percentage of polymorphic bands within different populations were 20.9%-55.0%. (3) The cluster map including all samples were obtained by UPGMA. In the map, there were six cluster groups and three individuals outside the groups. The branch with five samples of Zhongjiang Sichuan population were far from other samples in genetic distance. (4) According to the distribution provinces five groups were divided in genetic variance analysis. Genetic variance 80.44% existing within population, 8.29% among populations and 11.27% among groups. Conclusion (1) The genetic diversity within population of S. miltiorrhiza is plentiful. (2) The seeds of the cultivated population in Shandong and Henan Provinces come from the wild ones of same places. The cultivated plants lack artificial selection. The decrease of chemical compound is mainly due to the undesired condition of cultivating. (3) The genetic differentiation among the populations from different provinces is unbalance. Two population from Zhongjiang Sichuan and Chengde Hebei are far from the other population. (4) The genuineness of Radix Salviae Miltiorrhizae should be decided according to modern evaluation system. The herbs from some places of Shandong and Henan should be genuine ones.
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Objective To study the mechanism of blood-lipid regulation of the effective fractions from the extracts of Radix Salviae Miltiorrhizae(RSM)or Fructus Crataegi(FC),as well as their interaction.Methods The serum-drug of RSM and FC extracts were prepared by orthogonal design L_16(215).Amphotercin B cell model and RT-PCR method were used to examine the effects of the serum-drug of RSM and FC extracts on endogenous cholesterol biosynthesis in Chinese hamster ovary(CHO)cells and the expressions of cholesterol 7?-hydroxylase(CYP7A)mRNA in BRL cells.Results Ethanol(75%)and ammonia extracts of RSM obviously increased the absorbance(A)in the experiment of amphotercin B cell model and the expression of CYP7A mRNA in BRL cell line.The extracts of FC had no direct effect on cholesterol metabolism by themselves,but they were in synergism with the extracts of RSM.ConclusionThe extracts of RSM have a blood-lipid regulation by inhibiting endogenous cholesterol biosynthesis and increasing CYP7A mRNA expression,and maybe have a better effect when the extracts of FC are used together.
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Objective To select the optimum conditions of the vacuum belt drying process of Radix Salvia Miltiorrhiza(RSM) extract.Methods The process was studied by using orthogonal test design and grading method for multi-index on the parameters of the water content of dried product and drying rate of RSM extract,the average quantity of vapour during unit time span,as the index.Results The optimum process determined by the grading method was listed as follows: water content of the extract before drying was 40%,the feeding speed was 1.5 mL/s,the belt speed was 5 cm/min.Conclusion This technology can increase the average quantity of vapour during unit time span and the drying product has high quality with lower water content and desirable drying rate.
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Objective To establish the quality standard of Yifukang Capsule. Methods The identification of Radix Puerariae, Radix Salviae miltiorrhizae, Radix Ginseng was carried out by TLC. The content of puerarin was determined by HPLC. Results Radix Puerariae, Radix Salviae miltiorrhizae, Radix Ginseng could be identified by TLC. A good linearity of puerarin was in the range of 0.2～ 1.6 ? g(r=0.9999) and the average recovery of puerarin was 102.6 % , RSD was 1.70 % . Conclusion This method is simple, sensitive, accurate and with good reproducibility and can be used for the quality control of Yifukang Capsule.
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Objective To establish the quality control standard of Fufang Dangshen tablets. Methods Radix Codonopsis, Radix Salviae Miltiorrhizae and Radix Tinosporae in Fufang Dangshen tablets were identified by TLC. The content of tanshinoneⅡ A in Fufang Dangshen tablets was determined by HPLC. Results Radix Codonopsis, Radix Salviae Miltiorrhizae and Radix Tinosporae could be detected by TLC. TanshinoneⅡ A showed a good linear relationship in the a range of 0.050～ 0.451? g, r=0.9998. The average recovery was 97.48 % and RSD was 0.60 % . Conclusion The established methods are accurate, reproducible and can be used for the quality control of Fufang Dangshen tablets.
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Objective To observe the influence of heating method (or temperature control strategy) on the concentration of main active components in extracts from Radix Salviae Miltiorrhizae. Methods Common chromatographic peak area and the contents of Salvianolic acid B in three kinds of extracts obtained by 3 kinds of heating methods were compared. Results With the content of extracts extracted by the first heating method as the baseline, content of salvianolic acid B in extracts extracted by the second heating method was decreased 21.73 percent and that by the third method decreased 55.44 percent. Conclusion Quality of Salvianolic acid extracts can be affected greatly by temperature range and temperature control strategy. It is important to strictly control the heating method for the exaction of heat- sensitive active compounds from Chinese herbs.