Based on UHPLC-Q-TOF-MS and bioinformatics strategies, the potential allergens and mechanisms of allergic reactions caused by Danshen injection were explored.

The aim is to investigate the potential allergens and mechanisms underlying allergic-like reactions induced by Danshen injection (DSI). Utilizing ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS), metabolomics, and bioinformatics, we identified the key allergens, targets, and metabolic pathways involved in DSI-induced allergic-like reactions, validating binding efficiency through molecular docking and molecular dynamics. A total of 45 compounds were identified within DSI, with 24 compounds exhibiting strong binding activity to the MrgprX2 activation site. DSI was found to cause changes in 89 endogenous metabolites, including arachidonic acid, prostaglandins, and leukotrienes, primarily affecting pathways such as phenylalanine metabolism and arachidonic acid metabolism. The key allergens identified were Cryptotanshinone, Miltipolone, Neocryptotanshinone, Salvianolic acid B, and Isosalvianolic acid C, which primarily trigger allergic-like reactions by regulating upstream signaling targets such as ALOX5, PTGS1, PPARD, and LTB4R. Validation confirmed the high binding affinity and stability between key allergens and targets. These findings indicate that the allergic components in DSI primarily induce allergic-like reactions by modulating the aforementioned signaling targets, activating the AA metabolic pathway, promoting mast cell degranulation, and releasing downstream endogenous inflammatory mediators, subsequently eliciting allergic-like reactions.

Efficacy of Danshen injection combined with Calcitriol and Calcium/Vitamin-D for the treatment of osteoporotic fractures: A retrospective case-control study.

Objective: To explore the efficacy of Danshen injection combined with calcitriol and calcium/Vitamin-D in the treatment of osteoporotic fractures. Methods: This was a case-control study. We retrospectively reviewed clinical data of 91 patients with osteoporotic fractures who received treatment in Rui'an People's Hospital from February 2021 to July 2022. The data were divided into a control group with 44 records of patients who received treatment with calcitriol and calcium/Vitamin-D, and a study group with 47 patients who received Danshen injection combined with calcitriol and calcium/Vitamin-D. The control group individuals were coordinated with the patients in terms of their age and gender. Treatment effects, inflammatory response levels, and bone metabolic status levels were comparable between the two groups before and after the treatment. Results: The total efficacy of the treatment in the study group was better than that in the control group (P<0.05). After the treatment, levels of serum inflammatory factors in both groups decreased compared to those before the treatment, and the study group displayed lower levels than the control group (P<0.05). After the treatment, the bone metabolism status of both groups improved, and the improvement effect of the study group was better (P<0.05). The incidences of adverse reactions were similar in both groups (P>0.05). Conclusions: Danshen injection combined with calcitriol and calcium/Vitamin-D for the treatment of osteoporotic fractures can effectively reduce inflammation, regulate bone metabolism, and improve fracture treatment efficacy with a favorable safety profile.

[Systematic review of efficacy and safety of Compound Danshen Injection combined with Western medicine in treatment of vascular dementia].

To evaluate the efficacy and safety of Compound Danshen Injection combined with Western medicine in the treatment of vascular dementia. Databases of Cochrane Library, PubMed, EMbase, CNKI, SinoMed, VIP, Wanfang Data were electronically retrieved for collecting randomized controlled trial(RCT)about vascular dementia treated with Western medicine alone or combined with Compound Danshen Injection from the year of database establishment to January 2020. Two researchers independently screened out li-teratures, extracted data, and evaluated the risk of bias for inclusion in the study. Meta-analysis was conducted using RevMan 5.3 software. A total of 5 RCTs were included, involving 588 patients, with 299 in treatment group and 289 in control group. Meta-analysis results showed that compared with Western medicine alone, Compound Danshen Injection combined with Western medicine was better in the effective rate(RR=1.23,95%CI[1.14,1.33],P<0.000 01), MMSE score(MD=3.54,95%CI[3.01,4.06],P<0.000 01), ADL score(MD=11.49,95%CI[8.05,14.93],P<0.000 01), the level of CRP(MD=-0.72,95%CI[-1.25,-0.20],P=0.007) and the level of IL-6(MD=-7.64,95%CI[-9.65,-5.63],P<0.000 01). Adverse reactions mainly included rash and skin prick, which did not affect the treatment effect. Based on the findings, the combination of Compound Danshen Injection in the treatment of vascular dementia could improve the effective rates, relieve the mental state damage and improve the daily living ability, with mild adverse reactions and a low incidence. However, due to the low quality of the included literatures, high-quality and large-scale randomized controlled trials are needed for further verification.

[UPLC fingerprint combined with quantitative analysis of multi-components by single marker for quality assessment of Danshen Injection].

Testing and analysis of chemical markers is currently the prevailing approach for quality assessment of traditional Chinese medicines. However,several important issues remain to be addressed,including the trade-off between accuracy and coverage. In this study,in order to give full play to the advantages of their respective methods and provide technical support for more comprehensively and rapidly evaluate the quality of Danshen Injection products,a fingerprint method was coupled with quantitative analysis of multicomponents by single marker( QAMS),with Danshen Injection as the carrier. Ultra performance liquid chromatography( UPLC) was used to establish the quantitative fingerprint. The UPLC fingerprints contained 13 common peaks,11 of which were identified by using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-QTOF-MS). Furthermore,with sodium danshensu as the internal reference substance,relative correction factors( RCFs) of protocatechuic aldehyde,caffeic acid,rosmarinic acid,lithospermic acid,and salvianolic acid B were calculated through slope analysis method,and the QAMS method was adopted to determine the contents of these 6 components. The UPLC fingerprint was employed to assess the consistency of 12 batches of Danshen Injection,which showed good batch-to-batch consistency with similarity higher than 0. 99. In the comparison of contents of the six constituents obtained by QAMS and external standard method( ESM),RSD was all less than 4. 3%,indicating the good accuracy of the QAMS method. The QAMS method developed in this study combined with UPLC fingerprint can comprehensively reflect the internal quality of Danshen Injection when only the reference substance sodium danshensu is consumed,with greatly reduced detection cost and time. It provides a technical basis for further improving the quality standard of Danshen Injection.

Protective effects of Danshen injection against erectile dysfunction via suppression of endoplasmic reticulum stress activation in a streptozotocin-induced diabetic rat model.

BACKGROUND: Erectile dysfunction (ED) is a common complication of diabetes. This study aimed to explore the beneficial effect of Danshen injection on ED in a streptozotocin (STZ)-induced diabetic rat model and the underlying mechanism. METHODS: The diabetic rat model was established by an intraperitoneal injection of 60 mg/kg STZ in male Sprague-Dawley rats. The diabetic rats were intraperitoneally injected with Danshen solution (0.5 or 1 mL/kg/day) or the same volume of saline for 6 weeks. Age-matched rats served as controls. After 6 weeks, erectile function and histological morphology of the corpora cavernosum were assessed. Oxidative stress indicators, including superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and reactive oxygen species (ROS) levels, were measured in penile tissues. The expression levels of glucose-regulated protein 78 (Grp78), growth arrest and DNA damage-inducible gene 153 (GADD153/CHOP) were determined by immunohistochemistry, immunoblotting, and RT-PCR. Apoptosis was detected by a TUNEL assay. RESULTS: The erection times of diabetic rats were significantly less than those of control rats. Danshen injection could improve erectile function via increased erection times. Danshen injection was also found to ameliorate the morphological abnormalities of the corpora cavernosum, to reduce the number of apoptotic cells, and to suppress caspase-3 activation in penile tissue, accompanied by downregulation of the endoplasmic reticulum stress biomarkers Grp78 and CHOP. Danshen injection could increase SOD activity as well as reduce ROS and MDA levels in diabetic rats, indicating suppression of oxidative stress. CONCLUSION: Danshen injection could rescue diabetes-associated ED, possibly via suppressing the oxidative stress and endoplasmic reticulum (ER) stress-induced apoptosis pathways.

The Efficacy of Danshen Injection as Adjunctive Therapy in Treating Angina Pectoris: A Systematic Review and Meta-Analysis.

BACKGROUND: During the last 40 years, Danshen injection has been widely used as an adjunctive therapy for angina pectoris in China, but its efficacy is not yet well defined. The objective of this study was to verify the efficacy of Danshen injection as adjunctive therapy in treating angina pectoris. METHODS: The major databases including PubMed, Cochrane Library, Sino-Med, Medline, Embase, Google Scholar, China National Knowledge Infrastructure, Wanfang Databases, Chinese Scientific Journal Database, Chinese Biomedical Literature Database and the Chinese Science Citation Database were systematically searched for the published randomised controlled trials (RCTs) on Danshen injection until April 2016. Meta-analysis was conducted on the primary outcomes (i.e., the improvements in symptoms and electrocardiography (ECG)). The quality of the included RCTs was evaluated with the M scoring system (the refined Jadad scale). Based on the quality, year of publication and sample size of RCTs, sensitivity analysis and subgroup analysis were performed in this study. RESULTS: Ten RCTs, including 944 anginal patients, were identified in this meta-analysis. Compared with using antianginal agents (ß-blockers, calcium antagonists, nitrates, etc.) alone, Danshen injection combined with antianginal agents had a better therapeutic effect in symptom improvement (odds ratio [OR], 3.66; 95% confidence interval [CI]: 2.50-5.36) and in ECG improvement (OR, 3.25; 95% CI: 1.74-6.08). CONCLUSIONS: This study showed that Danshen injection as adjunctive therapy seemed to be more effective than antianginal agents alone in treating angina pectoris. However, more evidence is needed to accurately evaluate the efficacy of Danshen injection because of the low methodological quality of the included RCTs.

Simultaneous determination of eight Danshen polyphenols in rat plasma and its application to a comparative pharmacokinetic study of DanHong injection and Danshen injection.

Polyphenols derived from Danshen are responsible for the therapeutic effects of DanHong injection, a two-herb combination of Danshen and Honghua. Whether the pharmacokinetics of Danshen polyphenols is changed by coexisting Honghua constituents remains unknown. A sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed in this study for simultaneous determination of eight Danshen polyphenols (i.e., protocatechuic aldehyde, protocatechuic acid, tanshinol, salvianolic acid D, rosmarinic acid, salvianolic acid A, lithospermic acid, and salvianolic acid B) in rat plasma and applied to a comparative pharmacokinetic study of DanHong injection and Danshen injection. Liquid chromatography conditions, mass spectrometry parameters, and sample preparation were optimized step by step. The calibration curves showed good linearity (r > 0.99) for all the polyphenols. The mean extraction efficiencies ranged from 62.2 to 88.7% with negligible matrix effects. The intrabatch and interbatch precision at all the quality control levels were less than 15% of the nominal concentrations with accuracy of 88.8-114%, except that precision and accuracy at lower limit of quantitation were 3.2-17.3 and 95.7-119%, respectively. Comparative pharmacokinetic study suggested that the coexisting Honghua constituents might have negligible influences on the pharmacokinetics of Danshen polyphenols from DanHong injection. The bioanalytical method could also be applied to pharmacokinetic studies of other Danshen herbal products.

Multiple on-line HPLC coupled with biochemical detection methods to evaluate bioactive compounds in Danshen injection.

On-line high performance liquid chromatography (HPLC) coupled with three biochemical detection (BCD) methods was applied to evaluate bioactive components in Danshen injection. On-line HPLC-photo-diode array-fluorescence detection based on the fluorogenic substrate 7-acetoxy-1-methyl quinolinium iodide, was built to search acetylcholinesterase (AChE) inhibitors in Danshen injection. On-line HPLC coupled with the scavenging assay of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals was developed to screen antioxidants. The three active profiles were obviously different. Radical scavenging profiles revealed seven strong peaks in the chromatographic fingerprint possessing obvious free radical inhibition effects, while some minor peaks exhibited stronger AChE inhibition activities. The main radical scavengers and AChE inhibitors were identified by HPLC-MS. Several unknown ingredients showing strong AChE inhibition activities needed further identification except protocatechuic aldehydrate, salvianolic acid H or I and lithospermic acid. The on-line multiple on-line HPLC-BCD methods will provide powerful tools in the field of pharmacognosy for fast-track identification of interesting and/or novel bioactive compounds.

[Quality comparison andstructural characteristics of material basic composition of Danshen injection from different manufacturers].

HPLC was used to analyze the chromatographic fingerprints and determine the contents of tanshinol, protocatechuic acid, protocatechuic aldehyde, caffeic acid, isoferulic acid, lithospermic acid, rosmarinic acid, salvianolic acid B, salvianolic acid A, and salvianolic acid C in Danshen injection from 10 different manufacturers. The significant differences of phenolic compounds in Danshen injection from ten manufacturers were investigated by using F test. The results showed that the similarity degree of Danshen injection from ten manufacturers was above 0.9 and there was significant difference in mass fraction of phenolic compounds between the samples from different manufacturers. The analysis of mass fraction of effective phenolic components and their structural ratios in Danshen injection from the different manufacturers showed significant differences, indicating that the Danshen injection available in market had different curative effects and with significant differences in structural ratios.

[Effect of tripterygium glycosides and Danshen injection on blood coagulation mechanism in children with allergic purpura nephritis].

To observe the effect of tripterygium glycosides combined with Danshen injection on blood coagulation mechanism in children with allergic purpura nephritis, and investigate its treatment efficacy through a randomized controlled study. The results showed that before treatment, there were no significant differences in levels of D-D, APTT, PT, FIB and PLT between treatment group and control group; while after treatment, there were significant differences in levels of D-D, PT, FIB and PLT between two groups, but no difference in level of APTT. The effective rate was 90.38% in treatment group, significantly higher than 79.25% in the control group. There was no significant difference in incidence of adverse reactions between two groups. The results suggested that tripterygium glycosides combined with Danshen injection can enhance treatment efficacy and improve blood coagulation mechanism of children in the treatment of purpura nephritis, with high safety and no adverse effects.

Network Pharmacology along with Molecular Docking to Explore the Mechanism of Danshen Injection against Anthracycline-induced Cardiotoxicity and Transcriptome Validation.

INTRODUCTION: Although anthracyclines have demonstrated efficacy in cancer therapy, their utilization is constrained by cardiotoxicity. In contrast, Danshen injection (DSI), derived from Salvia miltiorrhiza, has a longstanding tradition of being employed to ameliorate cardiovascular ailments, including anthracycline- induced cardiotoxicity (AIC). Nonetheless, there is a notable dearth of comprehensive systematic investigation into the molecular mechanisms underlying DSI's effects on AIC. Consequently, this study was undertaken to explore the underlying mechanism by which DSI acted against AIC. METHODS: Employing network pharmacology approach, the current investigation undertook a comprehensive analysis of the impact of DSI on AIC, which was further validated by transcriptome sequencing with in vitro AIC model. Additionally, molecular docking was conducted to evaluate the binding of active ingredients to core targets. A total of 3,404 AIC-related targets and 12 active ingredients in DSI, including chrysophanol, luteolin, tanshinone IIA, isoimperatorin, among others, were collected by differentially expressed analysis and database search, respectively. RESULTS: The network pharmacology and enrichment analysis suggested 102 potential targets and 29 signaling pathways associated with the protective effect of DSI on AIC. Three core targets (CA12, NOS3, and POLH) and calcium signaling pathways were further validated by transcriptomic analysis of the in-vitro model. The high affinity of the active ingredients binding to corresponding targets was confirmed by molecular docking. CONCLUSION: The present study suggested that DSI might exert a cardioprotective effect on AIC via the inhibition of CA12, NOS3, and POLH, as well as the modulation of calcium signaling. Further experiments are warranted to verify the findings.

Development of a comprehensive method based on quantitative 1H NMR for quality evaluation of Traditional Chinese Medicine injection: a case study of Danshen Injection.

OBJECTIVES: This study aimed to establish a rapid and comprehensive method for quantitative determination of complex ingredients in Traditional Chinese Medicine injections. METHODS: A 1H quantitative nuclear magnetic resonance method was developed to simultaneously quantify comprehensive chemical components in Danshen Injection. Multivariate statistical analysis technique was applied to quality evaluation of multiple batches of Danshen injection. KEY FINDINGS: A complete signal attribution to the 1H nuclear magnetic resonance spectrum of Danshen injection was developed and performed for the first time. A total of 32 chemical components were identified from Danshen Injection. Among them, 20 were quantified simultaneously, accounting for up to 80% (w/w) of the total solids and 95% (w/w) of total organic matter, representing success compared to the previous studies. The developed method was further applied to analyze 13 batches of Danshen Injection from three manufacturers to make a realistic analysis. CONCLUSION: It was found that the comprehensive chemical information provides an adequate characterization for quality profiles among different commercial batches of Danshen Injection. The developed method further offered a guarantee for improving the consistency and safety of Traditional Chinese Medicine injections.

Danshen injection induces autophagy in podocytes to alleviate nephrotic syndrome via the PI3K/AKT/mTOR pathway.

BACKGROUND: Danshen injection (DSI) is an agent extracted from the Salvia miltiorrhiza Bunge, a natural drug commonly used to alleviate kidney diseases. However, the material basis and therapeutic effects of DSI on nephrotic syndrome (NS) remain unclear. PURPOSE: To investigate the material basis of DSI and the therapeutic effects and underlying mechanisms of NS. METHODS: NS models were established using adriamycin-induced BALB/c mice and lipopolysaccharide-induced mouse podocytes (MPC-5). Following DSI and prednisone administration, kidney coefficients, 24 h urine protein, blood urea nitrogen, and serum creatinine levels were tested. Histomorphology was observed by periodic acid-Schiff staining and hematoxylin and eosin staining of the kidney sections. The glomerular basement membrane and autophagosomes of the kidneys were observed using transmission electron microscopy. Nephrin and desmin levels in the glomeruli were tested using immunohistochemistry. The viability of MPC-5 cells was tested using cell counting kit-8 after chloroquine and rapamycin administration in combination with DSI. The in vivo and in vitro protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, phosphorylated AKT (Ser473), mammalian target of rapamycin (mTOR), microtubule-associated protein light chain 3 (LC3), beclin1, cleaved caspase-3, and caspase-3 were detected using western blotting. RESULTS: Our results showed that DSI contained nine main components: caffeic acid, danshensu, lithospermic acid, rosmarinic acid, salvianolic acid A, salvianolic acid B, salvianolic acid C, salvianolic acid D, and 3, 4-Dihydroxybenzaldehyde. In in vivo studies, the NS mice showed renal function and pathological impairment. Podocytes were damaged, with decreased levels of autophagy and apoptosis, accompanied by inhibition of the PI3K/AKT/mTOR signaling. DSI administration resulted in improved renal function and pathology in NS mice, with the activation of autophagy and PI3K/AKT/mTOR signaling in the kidneys. Additionally, podocytes were less damaged and intracellular autophagosomes were markedly increased. In vitro studies have shown that DSI activated MPC-5 autophagy and reduced apoptosis via the PI3K/AKT/mTOR pathway. CONCLUSION: Collectively, this study demonstrated that DSI activated podocyte autophagy and reduced apoptosis via the PI3K/AKT/mTOR signaling, ultimately attenuating NS. Our study clarified the main components of DSI and elucidated its therapeutic effects and potential mechanisms for NS, providing new targets and agents for the clinical treatment of NS.

The clinical efficacy of compound Danshen injection on acute cerebral infarction and on the changes in the CRP, D-dimer, and IL-6 levels.

OBJECTIVE: To study the clinical curative effect of compound Danshen injection on acute cerebral infarction (ACI) patients and its impact on the CRP, D-dimer, and IL-6 levels. METHODS: 116 patients with ACI admitted to our hospital were randomly placed in an observation group (n=58) or a control group (n=58). The control group received rosuvastatin tablets (10 mg/time, qd) in addition to the standard treatment. The observation group received compound Danshen injection in addition to the standard treatment. The treatment continued for 21 days. The clinical treatment efficacy, the CRP, D-dimer, and IL-6 levels, the NIHSS scores (to evaluate the degree of neurological impairment), the Fugl-Meyer scores (to access patients' motor function), the ADL scores, the sleep quality (the PSQI and AIS scores), and the complication incidence rates were compared between the two groups. RESULTS: After the treatment, the effective rate in the observation group (89.66%) was significantly higher than it was in the control group (74.14%) (P<0.05). After the treatment, the serum CRP, D-dimer, and IL-6 levels in the two groups were lower than they were before the treatment, and the levels were lower in the observation group than they were in the control group (all P<0.05). After the treatment, the NIHSS scores in the observation group were lower than they were in the control group, and the Fugl-Meyer and ADL scores were higher than they were in the control group (all P<0.05). Compared with the control group, the PSQI and AIS scores in the observation group were lower than they were in the control group after the treatment (P<0.05). The severe diarrhea, bedsore, urinary tract infection, liver and kidney function injury, skin allergic reactions and other total adverse reaction incidence rates in the observation group were lower than they were in the control group. CONCLUSION: Rosuvastatin combined with compound Danshen injection is effective in ACI treatment. It is able to effectively improve the clinical symptoms, reduce the incidence of complications, improve the recovery of the IL-6, CRP, and D-dimer levels and enhance patients' sleep quality.

Pre-treatment with a combination of Shenmai and Danshen injection protects cardiomyocytes against hypoxia/reoxygenation- and H2O2-induced injury by inhibiting mitochondrial permeability transition pore opening.

Increasing evidence has indicated that opening of the mitochondrial permeability transition pore (mPTP) has a vital role in myocardial ischemia/reperfusion (I/R) injury. Shenmai injection (SMI) plus Danshen injection (DSI) combination, termed Yiqi Yangyin Huoxue (YYH) therapy is used in the clinic to treat cardiovascular diseases, including myocardial I/R injury. Previous studies by our group have demonstrated the protective effect of pretreatment with YYH against myocardial I/R injury in isolated rat hearts. The present study aimed to examine the protective effect of YYH against hypoxia/reoxygenation (H/R)- and H2O2-induced cardiomyocyte injury, and to determine whether this effect is produced by inhibition of mPTP opening. Primary cardiomyocytes isolated from neonatal rats were cultured and randomly grouped into a control group, injury group and pretreatment group, with six duplicated wells in each group during each assay. Cardiomyocytes in the injury group were subjected to H/R to simulate I/R or exposed to H2O2 for 2 h to induce oxidative injury. Cellular injury was assessed via release of creatine kinase (CK) and lactate dehydrogenase (LDH), and cell viability was measured by an MTT assay. The mitochondrial membrane potential (ΔΨm) and cytosolic reactive oxygen species (ROS) were detected using the fluorescent probes rhodamine123 (Rh123) and chloromethyl-2,7-dichlorodihydrofluorescein diacetate (CM-H2DCFDA), respectively. Intracellular Ca2+, mitochondrial Ca2+ and mPTP opening were measured using fluo-4 acetoxymethyl (Fluo-4/AM), rhodamine-2 acetoxymethyl (Rhod-2/AM) and calcein acetoxymethyl (Calcein/AM) probes, respectively. The results indicated that pretreatment with YYH enhanced cell viability, increased ΔΨm, reduced CK and LDH release, and decreased intracellular ROS and Ca2+, thus reducing cardiomyocyte injury induced by H/R or H2O2. LY294002, a specific phosphoinositide 3-kinase (PI3K) inhibitor, and PD98059, a specific inhibitor of the extracellular signal-regulated kinase 1/2 (Erk1/2) pathway, eliminated the protective effects of the combination therapy on cell viability and the change in the ΔΨm in cardiomyocytes. In conclusion, pre-treatment with YYH has cardioprotective effects against H/R injury and oxidative stress via activation of the PI3K/Akt and Erk1/2 signaling pathways, which reduces mPTP opening, overproduction of ROS and calcium overload.

Effects of compound Danshen injection combined with magnesium sulfate on serum MPO and hs-CRP in patients with severe preeclampsia.

Effects of compound Danshen injection combined with magnesium sulfate on serum myeloperoxidase (MPO) and hypersensitive C-reactive protein (hs-CRP) in patients with severe preeclampsia (PE) were investigated. Five hundred patients with severe PE were randomly divided into early-onset observation, early-onset control, late-onset observation and late-onset control groups. Control group was treated with magnesium sulfate, while patients in observation group were treated with magnesium sulfate combined with compound Danshen injection. Serum levels of MPO and hs-CRP were measured by enzyme-linked immunosorbent assay (ELISA) and turbidimetric assay. The effects of compound Danshen injection combined with magnesium sulfate on the above indexes were observed. Serum levels of MPO and hs-CRP significantly decreased in early-onset observation, late-onset observation, early-onset control and late-onset control groups after treatment (p<0.05). After treatment, levels of MPO and hs-CRP were significantly lower in early-onset observation group than in early-onset control group (p<0.05), and levels of MPO and hs-CRP were also significantly lower in late-onset observation group than in late-onset control group (p<0.05). Total effective rate of early-onset observation group and late-onset observation group were higher than that of early-onset control group and late-onset control group. Compound Danshen injection combined with magnesium sulfate achieved better treatment outcomes in the treatment of severe PE than magnesium sulfate alone. The combined treatment can effectively reduce the serum levels of MPO and hs-CRP.

The effect of Danshen extract on lipoprotein-associated phospholipase A2 levels in patients with stable angina pectoris: study protocol for a randomized controlled trial - the DOLPHIN study.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2), a biomarker of oxidation and inflammation, has been associated with increased coronary artery disease risk. To date, very few studies have examined the Chinese herbal drug Danshen or its extract on Lp-PLA2 in patients with stable angina pectoris. In this study, we aim to investigate the effect of Danshen extract on Lp-PLA2 level in patients with stable angina. METHODS/DESIGN: This is a randomized, single-blind, placebo-controlled, adaptive clinical trial. A total of 156 patients meeting the eligibility criteria will be randomly assigned to either the Danshen extract (DanshenDuofensuanyan injection and Danshen drop spill) group or the placebo group in a 1:1 ratio. Participants will then undergo treatment with DanshenDuofensuanyan injection or placebo (glucose) during hospitalization, followed by open-label Danshen drop spill (30 pills/day) in Danshen extract group for 60 days after discharge. Because this is an adaptive trial, two interim analyses are prospectively planned. These will be performed after one-third and two-thirds of the patients, respectively, have completed the trial. On the basis of the results of these interim analyses, a data monitoring committee will determine how to modify aspects of the study without undermining the validity and integrity of the trial. The primary outcome measure is the serum level of Lp-PLA2 in the Danshen extract group and the placebo group. The secondary outcomes include the proportion of patients who show a clinically significant change, which is defined as at least a 20-point improvement in angina frequency score on the Seattle Angina Questionnaire and the carotid intima-media thickness, which will be measured using ultrasound. Other secondary efficacy and safety outcomes will also be assessed. DISCUSSION: This study will provide evidence that Danshen extract is beneficial for stable angina and may establish a possible mechanism of Danshen treatment effects on cardiovascular disease. This study may also validate an objective blood test (LP-PLA2 level) for assessing the effectiveness of Danshen therapy in patients with stable angina pectoris. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02870764 . Registered on 13 August 2016.

Danshen injection as adjuvant treatment for unstable angina pectoris: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the clinical effectiveness and safety of Danshen Injection (, DS) as one adjuvant treatment for conventional therapy with Western medicine (WM) for unstable angina pectoris (UAP). METHODS: Using literature databases, a thorough and systematic retrieval of randomized controlled trials (RCTs) comparing DS plus WM with WM was conducted from inception to April 2015. The extracted data from included studies was analyzed by Review Manager 5.2 software. The Cochrane risk of bias tool was used to assess the quality of included studies, and Begg's and Egger's tests conducted by Stata 12.0 were used to evaluate the potential presence of publication bias. RESULTS: A total of 17 RCTs, which involving 1,433 participants, were identified and reviewed. The meta-analysis indicated that the combined use of DS and WM was significantly superior to WM alone for UAP in terms of the total effectiveness rate of angina pectoris [risk ratio (RR) =1.23, 95% confidence interval (CI): 1.17, 1.29, P<0.01] and the total effectiveness rate of electrocardiogram (ECG) [RR=1.18, 95%CI: 1.06, 1.30, P=0.001]. Additionally, DS could also further reduce the content of fibrinogen, adjust blood lipid level, correct T wave inversion, and so on. Fifteen adverse drug reactions were reported in two studies, Four of which appeared in the experimental group. CONCLUSION: Based on the systematic review, the combined use of DS and WM was more effective than WM alone, it can be further widely used in clinic, however, there was no exact conclusion for its safety.

Analysis of phenolic acids by ionic liquid-in-water microemulsion liquid chromatography coupled with ultraviolet and electrochemical detector.

An environmentally friendly ionic liquid-in-water (IL/W) microemulsion was established and applied as mobile phase in microemulsion liquid chromatography (MELC) with ultraviolet (UV) detection or electrochemical detector (ECD) for analysis of phenolic compounds in real samples. The optimal condition of the method was using the best composition of microemulsion (0.2% w/v [HMIM]PF6, 1.0% w/v SDS, 3.0% w/v n-butanol, 95.8% v/v water, pH 2.5) with UV detection. The validation results indicated that the method provided high degree of sensitivity, precision and accuracy with the low limit of detections ranged from 17.9-238ng/mL, satisfactory mean recovery values in the range of 80.1-105% and good linearity (r2>0.9994). Additionally, this method exhibited high selectivity and resolution for the analytes and was more eco-friendly compared with traditional MELC method. Consequently, the established IL/W MELC method was successfully applied to simultaneously separate and determine target compounds in Danshen sample and its preparation.

Danshen injection ameliorates STZ-induced diabetic nephropathy in association with suppression of oxidative stress, pro-inflammatory factors and fibrosis.

Diabetic nephropathy (DN) is one of the most frequent complications in diabetes mellitus. This study aimed to explore whether Danshen injection is protective to renal tissue in diabetes. Intraperitoneal injection of streptozotocin (STZ) (60mg/kg) was used to induce diabetes in rats. Some STZ-induced diabetic rats were also intraperitoneally injected with Danshen solution at two different dosages (0.5 or 1ml/kg/day) for 6weeks. Our results showed that serum creatinine (sCr) and blood urea nitrogen were significantly increased in STZ-induced diabetic rats, which was alleviated upon Danshen injection. Danshen injection was also found to ameliorate hypertrophy and dilatation of renal tubule and glomeruli possibly by decreasing the expression of collagen and fibronectin in association with suppression of TGF-ß1/Smad pathway. Further investigation revealed that Danshen injection could increase the activity of superoxide dismutase (SOD), and reduce reactive oxygen species (ROS) and malondialdehyde (MDA) levels in STZ-induced diabetic rats, indicating suppression of oxidative stress. In addition, we also found that Danshen injection could suppress IκB/NF-κB signaling pathway and reduce the level of a number of pro-inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the diabetic renal tissue, indicating suppression of inflammation. In conclusion, our results demonstrated that Danshen injection may rescue STZ-induced diabetic nephropathy, possibly via suppressing the oxidative stress, inflammatory responses and fibrosis progression.