Compound Kushen injection induces immediate hypersensitivity reaction through promoting the production of platelet-activating factor via de novo pathway

OBJECTIVE Compound Kushen injection(CKI)is a bis-herbal formulation extracted from Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma Heterosmilacis Japonicae).Clinically,it is used as the adjuvant treatment of cancer.However,with the increased application,the cases of immediate hypersensitivity reactions(IHRs)also gradually rise.In this study,we investigated the underlying mechanism(s)and active constituent(s)for CKI-induced IHRs in experimental models.METHODS T helper 2(Th2)immunity-amplified mice were prepared by aluminum adjuvant.Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice.For evaluating microvascular permeability,Evans blue extravasation assay was used.Platelet-activating factor(PAF),serum total IgE(tIgE)and mouse mast cell protease 1(MMCP1)were measured by ELISA.RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks,but could induce Evans blue extravasation(local)and cause obvious hypothermia(systemic)after a single injection.Further study showed that alkaloids in Kushen,especially matrine,were responsible for CKI-induced IHRs.Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically.In cell system,CKI was able to promote PAF production in a non-cell-selective manner.In cell lysate,the effect of CKI on PAF production became stronger and could be abolished by blocking de novo pathway.CONCLUSION In conclusion,our study identifies,for the first time,that CKI is a PAF inducer.It causes non-immunologic IHRs,rather than IgE-dependent IHRs,by promoting PAF production through de novo pathway.Alkaloids in Kushen,especially matrine,are the prime culprits for IHRs.Our findings may provide a potential approach for preventing and treating CKI-induced IHRs.

Molecular mechanism prediction analysis of compound Kushen injection in the treatment of COVID-19 based on network pharmacology and molecular docking

Background:As one of the eight effective traditional Chinese medicines for the treatment of atypical pneumonia,compound Kushen injection(CKI)played an important role in combating pneumonia caused by severe acute respiratory syndrome coronavirus 2 virus in China in 2003.CKI is known to inhibit inflammation,and its main chemical components,namely matrine and oxymatrine,can promote Th cells to recognize and eliminate viruses.In this study,network pharmacology and molecular docking were used to explore the mechanisms of CKI for treating coronavirus disease 2019.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and other related literature were used to screen CKI’s active ingredients in the blood.Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,Swiss Target Prediction and STITCH were used to search for potential targets of the active ingredients.The“ingredient-target”network was constructed using the Cytoscape software.The STRING online database was used to construct a target protein-protein interaction network that can be visualized and analyzed using the Cytoscape software to obtain key targets.Results:Sophocarpine,sophoridine,matrine,(+)-allomatrine,AIDS211310,and sophranol were the six active ingredients.After docking the active ingredients with severe acute respiratory syndrome coronavirus 23CL hydrolase and angiotensin-converting enzyme 2(ACE2),they displayed suitable affinity,which could block viral replication and its binding to ACE2.The key targets mainly involved inflammatory factors,such as interleukin-6(IL-6)and tumor necrosis factor(TNF).Gene Ontology enrichment analysis mainly indicated the IL-6 cytokine-mediated signaling pathway and cytokine-mediated signaling pathway.The Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis mainly indicated steroid hormone biosynthesis and the TNF signaling pathway.Conclusion:The alkaloids in CKI can block viral replication and its binding to severe acute respiratory syndrome coronavirus 2 and ACE2 receptors.They regulate the IL-6-mediated signaling pathway,TNF signaling pathway,and steroid hormone biosynthesis,thereby initiating therapeutic responses against coronavirus disease 2019.

Microwave digestion polarography for determining seven trace elements in Salvia Miltiorrhiza Root and compound Salvia Miltiorrhiza Root injection simultaneously

The sensitive second derivative waves of Cu(Ⅱ),Pb(Ⅱ),Cd(Ⅱ),Ni(Ⅱ),Zn(Ⅱ),Fe(Ⅱ)and Mn(Ⅱ),forming in the substrate solution(pH=9.26)consisting of ammonia,ammonium chlorid,gelatin and ascorbic acid were researched.The peak potentials of the polarographic waves of the seven ions are at about 0.48,0.63,0.79,1.04,1.28,1.44 and 1.60 V respectively.Combining with microwave technique,a new method for the simultaneous determination of the seven trace elements in Chinese traditional medicine was developed.The method is easy to operate,rapid,simple and convenient.When the signal-to-noise rate equals 3,the detection limits of Cu,Pb,Cd,Ni,Zn,Fe and Mn are 4.2×10 3,5.3×10 3,2.1×10 3,5.8×10 4,3.0×10 3,7.7×10 4 and 1.1×10 3 μg/mL respectively.Well linear relationships exist between the concentrations and the peak currents when Cu,Pb,Cd,Ni,Zn,Fe and Mn concentrations are within 8.5×10 3 10,9.7×10 3 10,4.5×10 3 10,1.2×10 3 10,6.4×10 3 10,1.5×10 3 10 and 2.8×10 3 10 μg/mL,respectively.The method has been used to the simultaneous determination of the seven trace elements in Salvia Miltiorrhiza Root and compound Salvia Miltiorrhiza Root injection,the relative standard deviations(RSDs)of the Cu,Pb,Cd,Ni,Zn,Fe and Mn in the two medicines are 3.9% and 5.8%,4.0% and 4.1%,4.3% and 5.7%,4.9% and 5.3%,4.4% and 4.7%,3.5% and 4.0%,0.51% and 2.8%,respectively;the comparisons of the determination results with the values obtained by the standard method indicate that the presented method has very well veracity.

Mixture Preparation and Combustion of CNG Low-Pressure Compound Direct Injection Spark-Ignited Engines

A set of compressed natural gas (CNG) multi-point direct injection system of spark-ignited engines and the corresponding measurement and data acquisition systems were developed in this paper. Based on different injection modes, the mixture formation and combustion of CNG low-pressure direct injection (LPDI) engines were studied under varying factors such as air/ fuel ratio, injection timing. Meanwhile, three-dimensional simulations were adopted to explain the mixture formation mechanisms of CNG low-pressure compound direct injection (LPCDI) mode. On the basis of test results and simulation of the mixture homogeneous degree, the conception of injection window was proposed, and the LPCDI mode was proved to be more beneficial to the mixture concentration stratification formation in cylinder under lean-burning conditions, which resulted in effective combustion and stability.

Clinical study of Qiming granule combined with compound anisodine injection in the treatment of diabetic retinopathy

Objective:To investigate the clinical study of Qiming granule combined with compound anisodine injection in the treatment of diabetic retinopathy.Methods:104 patients with nonproliferative diabetic retinopathy admitted to department of ophthalmology in Xishui Hospital Affiliated to Hubei University of science and technology from September 2016 to May 2018 were selected as the study subjects.According to the principle of treatment,they were divided into 52 cases in the control group and 52 cases in the treatment group,the clinical efficacy,blood sugar and lipid levels,hemorheological changes and adverse reactions were compared between the two groups.Results:The total effective rate difference between the treatment group(92.31%)and the control group(71.15%)was statistically significant(χ^(2)=7.792,P=0.005).After treatment,the two groups of fasting plasma glucose(FPG),hemoglobin A1c(HbA1c),total cholesterol(TC),low density lipoprotein-cholesterol(LDL-C),whole blood high-viscosity,whole blood cut viscosity,whole blood low-cut viscosity,plasma viscosity,number of microangioma and area of the hemorrhage were significantly lower than before treatment(P<0.05),and the levels of FPG,HbA1c,TC,LDL-C,whole blood highviscosity,whole blood cut viscosity,whole blood low-cut viscosity,plasma viscosity,number of microangioma and area of the hemorrhage in the treatment group were significantly lower than those in the control group(χ^(2)=0.122,P=0.727).Conclusions:Qiming granule combined with compound anisodine injection can effectively improve the clinical efficacy of patients with non-proliferative DR,and its mechanism may be related to improve blood sugar and blood lipid levels and correct blood rheology disorder,reduce microangioma and hemorrhage.It has clinical promotion significance.

Effect of Compound Danshen Injection Combined with Labetalol on Liver Function and Placental Growth Factor in Patients with Eclampsia

Objective: To explore the effect of Compound Danshen Injection combined with Labetalol on liver function and placental growth factor in patients with eclampsia. Methods: Seventy patients with eclampsia who were treated in the Hospital from February 2017 to February 2019 were enrolled. The patients were divided into two groups according to the random number table, with 35 cases in each group. The Observation group was treated with Labetalol, and the combined therapy group was treated with Compound Danshen Injection combined with Labetalol. The liver function [alanine aminotransferase, aspartate aminotransferase, total protein, and albumin], hemorheology indicators, placental growth factor and serum insulin-like growth factor-1 and clinical indicators in the two groups were analyzed. Results: After treatment, the levels of alanine aminotransferase and aspartate aminotransferase in the combined therapy group were significantly lower than those in the Observation group. The levels of total protein and albumin in the combined therapy group were significantly higher than those in the Observation group (P<0.05). After treatment, the high-cut and low-cut whole blood viscosity, plasma viscosity and erythrocyte rigidity index in the combined therapy group were significantly lower than the Observation group, and the difference was statistically significant (P<0.05). After treatment, the levels of PLGF and IGF-1 in the combined therapy group were significantly higher than those in the Observation group, and the difference was statistically significant (P<0.05). After treatment, the gestational age, neonatal weight index, placental weight and neonatal 1 min Apgar score in the combined therapy group were significantly higher than the Observation group, and the difference was statistically significant (P<0.05). Conclusion: For patients with eclampsia, Compound Danshen Injection combined with Labetalol is with great safety, which can help stabilize their condition, and improve their liver function and placental growth factor status.

Research Progress on the Antitumor Mechanism of Compound Kushen Injection

Compound Kushen Injection(CKI),as a clinical traditional Chinese medicine preparation,has prominent antitumor effect but with several side effects.A large number of studies have shown that CKI plays an antitumor role by regulating tumor cell proliferation,inducing tumor cell differentiation and apoptosis,inhibitrng tumor cell invasion and metastasis,reducing tumor angiogenesis,regulating the immunity,and so on.Clinically,CKI is widely used to treat various tumors,where it is often combined with surgery,chemotherapy,radiotherapy,targeted therapy,and other antitumor treatments.This article reviews the antitumor mechanism of CKI and the progress of its clinical application in order to provide a theoretical basis for further clinical application.

TREATMENT OF 40 CASES OF CHRONIC ECZEMA WITH POINT-INJECTION OF COMPOUND RADIX SALVIAE MILTIORRHIZAE INJECTION

The authors have used point-injection of compound Radix Salviae Miltiorrhizae Injection to treat 40 cases of chronic eczema and achieved a satisfactory therapeutic effect. The total effective rate was 95%.

Effect of compound Kushen injection on T-cell subgroups and natural killer cells in patients with locally advanced non-small-cell lung cancer treated with concomitant radiochemotherapy

OBJECTIVE: To observe effect of compound Kushen injection on T-cell subgroups and NK cells in patients with locally advanced non-small-cell lung cancer(NSCLC) treated with concomitant radiochemotherapy.METHODS: We randomly divided 60 patients with locally advanced NSCLC who were treated at our hospital between May 2011 and May 2013 into a treatment group and a control group by drawing.The treatment group(n = 30) received concomitant radiochemotherapy plus compound Keshen injection, and the control group(n = 30) received only radiochemotherapy.RESULTS: After treatment, levels of CD3+, CD4+,CD4 +/CD8 + and CD16 +/CD56 + cells had significantly increased, and CD8 + cells had significantly decreased, in the treatment group compared with both their pretreatment levels and with levels in the control group. In the control group, post-treatment levels of CD3 +, CD4 +, CD4 +/CD8 + and CD16+/CD56+ cells were not significantly changed from pretreatment levels. The two groups did not significantly differ in their rates of toxicity reactions(P > 0.05).CONCLUSION: Compound Kushen injections can increase immunologic function in patients with locally advanced non-small cell lung cancer who receive concomitant radiochemotherapy.

Effect of Compound Glycyrrhizin Injection on Liver Function and Cellular Immunity of Children with Infectious Mononucleosis Complicated Liver Impairment

Objective： To investigate the effects of Compound Glycyrrhizin Injection （CGI） on liver function and cellular immunity of children with infectious mononucleosis complicated liver impairment （IM-LI） and to explore its clinical therapeutic effect. Methods： Forty-two patients with IM-LI were randomly assigned, according to the randomizing number table, to two groups, 20 in the control group and 22 in the treated group. All the patients were treated with conventional treatment, but to those in the treated group, CGI was given additionally once a day, at the dosage of 10 ml for children aged below 2 years, 20 ml for 2-4 years old, 30 ml for 5-7 years old and 40 ml for 8- 12 years old, in 100-200 ml of 5% glucose solution by intravenous dripping. The treatment lasted for 2 weeks. T lymphocyte subsets and serum levels of alanine transaminase （ALT）, aspartate aminotransferase （AST） and total bilirubin （TBil） were detected before and after treatment. Besides, a normal control group consisting of 20 healthy children was also set up. Results： Baseline of the percentage of CD3^＋ , CD8^＋ lymphocyte and serum levels of ALT, AST, TBiL in the children with IM-LI were markedly higher, while the percentage of CD 4^＋ lymphocyte and the CD4^＋/CD8^＋ ratio was markedly lower in IM-LI children as compared with the corresponding indices in the healthy children （ P〈0.01 ）. These indices were improved after treatment in both groups of patients, but the improvement in the treated group was better than that in the control group （P〈0.01）. Conclusion： Cellular immunity dysfunction often occurs in patients with IM-LI, and CGI treatment can not only obviously promote the recovery of liver function, but also regulate the immune function in organism.

Efficacy and mechanism of a compound epirubicin plus quinine injection for the treatment of drug--resistant breast cancer

A single drug chemotherapy fails to eliminate residual cancer cells due to the existence of the multidrug resistance （MDR）. In the present study, we aimed to develop a compound epirubicin plus quinine injection, to characterize the efficacy in treatment of the drug-resistant breast cancer, and to reveal the involved mechanisms. The HPLC-UV methods were developed for quantifications, and the evaluations were performed on the drug-resistant human breast cancer MCF-7/adr cells using a high content screening system. Results demonstrated that the compound epirubicin plus quinine injection was able to effectively block the drug efflux, exhibiting an evidently overall efficacy in treatment of the resistant breast cancer cells by direct killing effect and by apoptosis-inducing effect. In the formulation, quinine played multiple roles in blocking drug efflux and in inducing the apoptosis of the resistant breast cancer cells. The apoptosis signaling pathways were associated with a cascade of reactions by activating Caspase family and by inhibiting Bcl-2 family. In conclusion, the present study preliminarily revealed the efficacy and mechanism of the compound epirubicin plus quinine formulation in treatment of the drug-resistant breast cancer, and offered a potential strategy to overcome drug resistance in cancer treatments.

Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation

Bladder cancer is the most common malignancy of the urinary system.Compound Kushen Injection(CKI)is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades.However,the pharmacological effect of CKI on bladder cancer is not still completely understood.In the current study,network pharmacology com-bined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer.The mech-anism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24.Net-work pharmacology analysis identified 35 active compounds and 268 target genes of CKI.Bioinformatics data indicated 5500 differen-tially expressed genes associated with bladder cancer.Common genes of CKI and bladder cancer suggested that CKI exerted anti-blad-der cancer effects by regulating genes such as MMP-9,JUN,EGFR,and ERK1.Functional enrichment analysis indicated that CKI ex-erted therapeutic effects on bladder cancer by regulating certain biological processes,including cell proliferation,cell migration,and cell apoptosis.In addition,Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer,bladder cancer,and the PI3K-Akt signaling pathway.Consistently,cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells,and induced their apoptosis.Moreover,RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9,JUN,EGFR,and ERK1.CKI inhibited the prolif-eration and migration,and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets.CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer.Overall,our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer,and further support its clinical use.

Effects of Compound Salviae Miltiorrhizae Injection on Metabolism of Phosphoinosititides in Myocardial Ischemia

Using the model of acute myocardial ischemia in rats formed by ligation of the descending an-terior branch of the left coronary artery, this study showed some effects of compound Salviae miltiorrhizae in-jection ( CSMI) on metabolism of phosphoinositide in myocardial ischemia. The results of the experimentshowed that after 10 minutes of acute ischemia, the function of myocardial messangers ot phosphoinositide in-creased, and the levels of phosphatidylinositol-4, 5-biphosphate ( PIP2 ) and inositol-1, 4, 5-trisphosphate(IP3 ) were obviously higher than those of the non-ischemia control groups ( P < 0. 01 , n = 7) . CSMI (2 glkgbody weight) could markediy inhibit myocardial PIP2 and IP3, whose levels became lower than those of theischemia control groups ( P < 0 . 01 , n = 7 ) .

Clinical Study of Compound Radix Salvia Miltiorrhizae for Severe Pancreatitis

Compound Radix Salvia Miltiorrhizae injection was administered after operation for 28 casesof severe pancreatitis, and 13 cases were taken as a control group. The results showed that : (1) The differ-ence was not obvious in the morbidity of complications between the two groups, but the mortality (3.6% ) ofthe trial group was significantly lower tlian that ( 30. 8% ) of the control group ( P < 0. 05 ) ; ( 2 ) Hematocritwas clearly decreased from 46. 1 5. 2% to 33. 2 3. 9% in the trial one ( P < 0. 05) , but platelet andhemoglobin showed no statistical signiticance. It is concluded that compound Salvia miltiorrhizae inlectionmight improve hemorheologic abnormalities of the disease, promote the recovery of the pancreatic tissue,and correct the serious complications such as adult respiratory distress syndrome etc.