Compound Danshen tablets downregulate amyloid protein precursor mRNA expression in a transgenic cell model of Alzheimer's disease Effects and a comparison with donepezil

After gene mutation, the pcDNA3.1/APP595/596 plasmid was transfected into HEK293 cells to establish a cell model of Alzheimer＇s disease. The cell model was treated with donepezil or compound Danshen tablets after culture for 72 hours. Reverse transcription-PCR showed that the mRNA expression of amyloid protein precursor decreased in all groups following culture for 24 hours, and that there was no significant difference in the amount of decrease between donepezil and compound Danshen tablets. Our results suggest that compound Danshen tablets can reduce expression of the mRNA for amyloid protein precursor in a transgenic cell model of Alzheimer＇s disease, with similar effects to donepezil.

Study on Determination of Tanshinones in Compound Danshen Tablets

[ Objective ] This study was conducted to improve quality standard of Compound Danshen tablets. [ Method] Tanshinones in Compound Danshen tab- lets were determined by HPLC method. [ Result] A good linear relationship was found in the range of 0.10 -0.50 μg, and the average recovery rate was 100.59% （RSD = 1.38% ）. [ Conclusion] The method is simple, rapid and reproducible, and could be used as a method for quality control of Compound Danshen Tablets.

Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery

AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS: LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation,such as diameters of arterioles and venules,velocity of RBCs in venules,leukocyte rolling,adhesion and emigration,free radicals released from post-capillary venules,FITC- albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile,the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils,and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro. RESULTS: The continuous infusion with LPS resulted in a number of responses in microcirculation,including a significant increase in the positive region of venulestained with Monastral blue B,rolling and adhesion of leukocytes,production of oxygen radical in venular wall,albumin efflux and enhanced mast cell degranulation in vivo,all of which,except for the leukocyte rolling,were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils,and the expression of ICAM-1 in HUVECs were increased by exposure to LPS,and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance.

The Protective Effect of Compound Danshen Dripping Pills on Oxidative Stress after Retinal Ischemia/Reperfusion Injury in Rats

Objective: To investigate the effect of Compound Danshen Dripping Pills (CDDP) on oxidative stress after ischemia/reperfusion (I/R) injury in the rat retina. Methods: Adult male SD rats were randomly divided into 3 groups: sham (group A), I/R (group B), and I/R plus CDDP (group C). Retinal ischemia/reperfusion injury (RIRI) was introduced by increasing the intraocular pressure (IOP) to 110 mmHg for 60 min via cannulation into the anterior chamber. Right after the insult, CDDP was administered intragastrically (450 mg/kg/d) for 7 days. The levels of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the retinal tissues were determined on d1 and d7 after the ischemic insult. Results: Following ischemia, the MDA levels in group B and group C were significantly higher than those in group A (p < 0.01). CDDP significantly lowered MDA levels in group C when compared with group B (p < 0.01). The activities of SOD, GSH-Px and CAT were higher in group A than in group B and group C (p < 0.01). CDDP could increase the activities of SOD, GSH-Px and CAT remarkably in group C when compared with group B (p < 0.01). Conclusion: CDDP can protect the retina from I/R injury through reducing oxidative stress, and thus may be a promising method for the treatment of ischemic retinal disorders.

Compound Chaijin Jieyu Tablets ameliorating insomnia complicated with depression by improving synaptic plasticity via regulating orexin A,melatonin,and acetylcholine contents

Objective To investigate the efficacy and mechanism of action of Compound Chaijin Jieyu Tablets(复方柴金解郁片,CCJJYT)in rats with insomnia complicated with depression.Methods Seventy-two Sprague-Dawley rats were randomly assigned into eight groups:the control,chronic unpredictable mild stress(CUMS),sleep deprivation(SD),CUMS+SD,positive drug(venlafaxine hydrochloride+diazepam),CCJJYT high-dose(CCJJYT˗2×),medium-dose(CCJJYT˗1×),and low-dose(CCJJYT˗0.5×)groups,with nine rats in each group.Depression-like behavior was evaluated by body weight,food intake,and behavioral tests such as the sucrose preference test(SPT),open field test(OFT),forced swimming test(FST),and pentobarbital-induced sleep test(PST).Hematoxylin-eosin(HE)staining and Golgi-Cox staining were used to observe changes in pathological tissue and synaptic morphology,respectively.Enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of orexin-A and acetylcholine.The expression levels of orexin receptor 1(OXR1),melatonin receptor 1(MT1A),melatonin receptor 2(MT1B),acetylcholinesterase(AChE),and choline acetyltransferase(ChAT)were detected by immunohistochemistry and Western blot.Results In the present study,rats in the model group showed significant behavioral changes as well as a reduction in hippocampal dendritic branch length and synaptic number,along with increasing the content of orexin A and acetylcholine(P<0.05),and altered expression levels of OX1R,MT1A,MT1B,ChAT,and AChE in the hippocampus and prefrontal cortex after modeling(P<0.05).CCJJYT can improve depressive insomnia behavior and synaptic plasticity of rats(P<0.05),which is similar to that of the positive drug group.It can also decrease the content of orexin A and acetylcholine,and reduce the expression levels of OXR1 and ChAT in hippocampus and prefrontal cortex(P<0.05),and increase the expression levels of MT1A,MT1B,and AChE proteins(P<0.05).Conclusion CCJJYT has good antidepressant and insomnia effects,probably through the regulation of orexin-A,melatonin,and acetylcholine content in hippocampus and prefrontal cortex of rats,improving synaptic plasticity and thus exerting antidepressant and insomnia effects.

Compound Chai Jin Jie Yu Tablets,Acts as An Antidepressant by Promoting Synaptic Function in the Hippocampal Neurons

Objective To investigate the effectiveness of compound Chai Jin Jie Yu Tablets(CJJYT)in ameliorating cognitive impairment associated with depression and its potential mechanism of action.Methods In vitro experiments,the hippocampus was isolated from the whole brain of the fetal rat and cultured into hippocampal neuron cells.50μM corticosterone(CORT)was added to each group 18 h before the experiment for modeling depression,with the exception of the control group.After modeling,the blank serum group was added with 10%blank serum,the CJJYT group and the venlafaxine group were added with the corresponding 10%drug-containing serum,and the control group and the model group were added with equal volumes of culture medium.The intracellular Ca^2+mean fluorescence intensity,miniature excitatory postsynaptic current(mEPSC)current amplitude,and frequency of different hippocampal neurons were evaluated as indicators of synaptic function in the hippocampal neurons.In addition,the expression of synaptic plasticity related proteins,synaptophysin-α(SYN-α),N-methyl-D-aspartate receptor 2A(NR2A),N-methyl-Daspartate receptor 2B(NR2B),post synaptic density 95 protein(PSD-95),calcium/calmodulin dependent protein kinaseⅡ(CaMKⅡ)and synaptic associated protein(SynGAP)were detected in the hippocampal neurons by immunofluorescence staining and high content analysis(HCA)system.Then,reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the mRNA expression levels of SYN-α,NR2A,NR2B,PSD-95,CaMKⅡand SynGAP.For in vivo experiments,except for those in the blank control group,all rats were treated within a single cage for chronic unpredictable stress-induced depression modeling and subjected to corresponding drug interventions.Behavioral tests were used to detect depressive behavior and determine learning,memory and other cognitive abilities,whereas enzyme-linked immunosorbent assay(ELISA)was used to detect the CORT levels.Golgi-Cox staining was used to observe changes in the synaptic morphology of parahippocampal gyrus CA1 area(CA1)and dentategyrus(DG).Results In vitro,CJJYT treatment reduced the intracellular Ca^2+mean flurorescence intensity in the hippocampal neurons(P<0.05),causing a reduction in the frequency and current amplitude of mEPSC(P<0.05),and thus inhibited the excessive activation of post-synaptic receptors.CJJYT treatment reduced the protein and mRNA expression of SYN-α,NR2A,NR2B and PSD-95 in the hippocampal neurons(P<0.05),increased the mRNA and protein expression of CaMKⅡand SynGAP(P<0.05),and thereby improved the synaptic plasticity of the hippocampal neurons.In vivo,CJJYT intervention improved sucrose preference,voluntary activity,learning and memory ability of Morris water maze test,and suppressed appetite(P<0.05),and increased the despair feeling of forced swimming test(P<0.05).The CORT level was reduced(P<0.05),leading to the repair of synaptic damage in the hippocampal neurons.Conclusions CJJYT can improve the synaptic function of hippocampal neurons and has obvious protective effects on neurons.It can repair the structural damage in the hippocampal neurons,improving the cognitive ability of the depressed model rats.The mechanism of CJJYT improving cognition in depressed rats may be related to the transmission and function of SYN-α/NR and its downstream neurotransmitters.

Protective Effects of Self-made Compound Taoren Danshen Decoction on Rats with Acute Liver Injury

[Objectives] To study the protective effects of self-made Compound Taoren Danshen Decoction( CTDD) on acute liver injury induced by D-galactosamine in rats,and to explore its mechanism. [Methods]An acute liver injury model was established by intraperitoneal injection of 500 mg/kg of D-galactosamine. The ALT,AST,MDA,SOD and GSH-Px in serum,as well as serum TNF-α,IL-1β and IL-6 levels were measured,and liver tissue lesions were observed under microscope. [Results] CTDD can significantly reduce ALT,AST and MDA levels,increase SOD,GSH-Px activity,and significantly reduce serum TNF-α,IL-1β and IL-6 levels,and improve liver tissue lesions.[Conclusions]CTDD has a protective effect on D-galactosamine-induced acute liver injury in rats,and its mechanism may be related to inhibition of oxidative stress and inflammatory reaction.

Semi-quantitative analysis on the content of berberine hydrochloride in compound berberine tablets with the fluorescence spectral imaging method

The content of berberine hydrochloride(BH)in compound berberine tablets(CBTs)is subject to strict requirements.Its content is usually measured based on chemical analysis.In this paper,the fluorescence spectral imaging method was used to study the relative content of BH from a physics perspective.By comparing the relative fluorescence intensity of self-made CBTs with di®erent mass percentages of BH,a linear positive relationship was observed between the BH content and the relative fluorescence intensity,and accordingly the quality of CBTs of different brands was evaluated.The results indicate that the fluorescence spectral imaging method can be a simple,fast and nondestructive semi-quantitative analysis method to determine the content of BH in CBTs,and this method has great potential in the quality control of CBTs.

Clinical Intervention Effect of Compound Danshen Dripping Pills on Aspirin Resistant Patients with Coronary Heart Disease

[Objectives]To study the clinical intervention effect of Compound Danshen Dripping Pills on aspirin-resistant patients with coronary heart disease(CHD).[Methods]240 patients with coronary heart disease who took Aspirin were selected to measure thrombocytopenia by sonoclot.They were randomly divided into four groups:group A(n=60),Compound Danshen Dripping Pills and aspirin.group B(n=60),aspirin;group C(n=60),high dose aspirin;group D(n=60),Compound Danshen Dripping Pills.CR and PF were determined by sonoclot after one month.The incidence of angina pectoris,acute myocardial infarction,sudden cardiac death and hemorrhage were observed.[Results]After treatment,the CR and PF levels of group A and C were significantly lower than those before treatment,and there was no significant difference between group B and D and before treatment.After treatment,the levels of CR and PF in group A and C were significantly lower than those in group B and D,and there was a significant difference.Angina pectoris and myocardial infarction events in group D were significantly higher than the other four groups;hemorrhage events in group C were significantly higher than the other three groups.[Conclusions]Compound Danshen Dripping Pills combined with aspirin can be used as an economical,effective,and more dependent alternative to inhibit platelet activity in aspirin resistance,and can further reduce the occurrence of acute coronary events.

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.

Pseudo-hyperaldosteronism caused by compound glycyrrhizin tablets: a case report

Compound glycyrrhizin tablets(CGT)is a glycyrrhizin-containing preparation for the treatment of chronic hepatic diseases,it contained Glycyrrhizin,Monoammonium Glycyrrhizinate,Aminoacetic Acid and Methionine.CGT has been shown to have anti-inflammatory,anti-oxidative,and anti-viral effects.Although pseudo-hyperaldosteronism was reported as its important side effects,the frequency was unknown.A 59-year-old male patient with tuberculous pleurisy received CGT to prevent impairment in liver function which was caused by antituberculosis drugs.After more than one month,it appeared edema in the lower extremity,blood pressure increased,serum potassium lowed,serum sodium raised at the normal high limit.Finally,it was improved by suspending the CGT and diuretic treatment.

Effect of Compound Biejiaruangan Tablets combined with entecavir therapy on liver fibrosis process and immune response state in patients with chronic hepatitis b

Objective:To study the effect of Compound Biejiaruangan Tablets combined with entecavir therapy on liver fibrosis process and immune response state in patients with chronic hepatitis b.Methods: Patients with chronic viral hepatitis b who were treated in the Affiliated Hospital of Inner Mongolia Medical University between May 2015 and March 2017 were selected as the research subjects and divided into the combined group who accepted Compound Biejiaruangan Tablets combined with entecavir therapy and the control group who accepted entecavir monotherapy. The contents of collagen metabolism indexes and inflammatory response molecules in serum as well as the contents of immune cells in peripheral blood were determined before treatment and 24 weeks after treatment.Results: 24 weeks after treatment, PC-III, C-IV, MMP1, MMP2, TIMP1, IL-1β, IL-18, MIF, RANTES, MIP-1 and MIP-1β contents in serum as well as Th2, Treg and Th17 contents in peripheral blood of both groups of patients were significantly lower than those before treatment whereas Th1 contents in peripheral blood were significantly higher than those before treatment, and PC-III, C-IV, MMP1, MMP2, TIMP1, IL-1β, IL-18, MIF, RANTES, MIP-1 and MIP-1β contents in serum as well as Th2, Treg and Th17 contents in peripheral blood of combined group of patients were significantly lower than those of control group whereas Th1 content in peripheral blood was significantly higher than that of control group.Conclusion: Compound Biejiaruangan Tablets combined with entecavir therapy can delay the liver fibrosis process and improve the immune response state in patients with chronic hepatitis b.

Effects of Compound α-Ketoacid Tablets on renal function, renal fibrosis indexes and oxidative stress in patients with diabetic nephropathy

Objective: To investigate the effects of Compound α-Ketoacid Tablets on renal function, renal fibrosis indexes and oxidative stress in patients with diabetic nephropathy. Methods: A total of 180 patients with diabetic nephropathy admitted to Nephrology Department of our hospital were randomly divided into control group and observation group, 90 cases in each group. The patients in the control group were given conventional treatment, such as antihypertensive drugs, diet and blood glucose control, and the patients in the observation group were given Compound α-Ketoacid Tablets on the basis of the control group. Renal function, renal fibrosis index and oxidative stress levels were compared between the two groups before and after treatment. Results: After treatment, the levels of serum ALB, BUN, Cr, Hcy, VEGF and MDA in two groups were significantly decreased than those before the treatment, and the levels of ALB, Hcy, VEGF and MDA in the observation group were significantly lower than those in the control group, the difference was statistically significant. After treatment, the levels of serum GFR, HGF, T-AOC and SOD in two groups were significantly increased than that before the treatment, and the levels of HGF, T-AOC and SOD in the serum of the observation group were significantly higher than that in the control group, the difference was significant. Conclusion:The Compound α-Ketoacid Tablets has good effect in the treatment of diabetic nephropathy. It can effectively improve the state of renal fibrosis and reduce the oxidative stress reaction of the patients, so as to achieve the protection of the kidney.

Effects of tripterygium glycosides combined with compoundα-keto acid tablets on inflammatory response, oxidative stress and urinary TGF-β1, IV-C levels in patients with chronic renal failure

Objective:To investigate the effects of tripterygium glycosides combined with compoundα-ketoacid tablets on inflammatory response, oxidative stress and urinary TGF-β1 and IV-C levels in patients with chronic renal failure.Methods: 102 patients with chronic renal failure admitted to Shuguang hospital from January 2017 to June 2018 were randomly divided into observation group (51 cases) and control group (51 cases). In the control group, the tripterygium glycosides tablets were orally administered, and the observation group was orally administered with tripterygium glycosides tablets and compoundα-keto acid tablets. The inflammatory response, oxidative stress index and urinary TGF-β1, IV-C levels were compared between the two groups.Results: There was no significant difference in CRP and TNF-α levels between the two groups before treatment (P>0.05). After treatment, the levels of CRP and TNF-α in the observation group were (9.32±1.10) mg/L and (3.14±0.36) ng/L, respectively, and the levels of CRP and TNF-α in the control group were (15.34±1.31) mg/ L, (5.01±0.53) ng / L. The CRP and TNF-α levels in the two groups were lower than those before treatment, and the CRP and TNF-α in the observation group were significantly lower than those in the control group (P<0.05). Before treatment, there was no significant difference in MDA, SOD and GSH-PX levels between the two groups (P>0.05). After treatment, the MDA level of the observation group was (3.01±0.32) μmol/L, and the MDA level of the control group was (5.17±0.61) μmol/L. The MDA of the two groups was lower than that before treatment, and the MDA of the observation group was significantly lower than that of the control group (P<0.05). After treatment, the levels of SOD and GSH-PX in the observation group were (101.45±13.16) U/L and (94.83±7.17) U/L, respectively. The levels of SOD and GSH-PX in the control group were (88.87±12.05) U/L, (87.38 ± 6.32) U/L. The SOD and GSH-PX of the two groups were higher than those before treatment, and the SOD and GSH-PX of the observation group were significantly higher than the control group (P<0.05). Before treatment, there was no significant difference in TGF-β1 and IV-C levels between the two groups (P>0.05). After treatment, the levels of TGF-β1 and IV-C in the observation group were (1.05±0.24) ng/L and (5.05±1.13) μg/L, respectively, and the levels of TGF-β1 and IV-C in the control group were (1.36±, respectively). 0.26) ng/L, (7.07±1.24) μg/L. The levels of TGF-β1 and IV-C in the two groups were lower than those before treatment, and the TGF-β1 and IV-C in the observation group were significantly lower than those in the control group (P<0.05).Conclusion: Tripterygium glycosides combined with compound -keto acid tablets can effectively reduce the inflammatory response, oxidative stress and renal interstitial fibrosis in patients with chronic renal failure.

Effects of compound danshen dripping pills on the levels of serum inflammatory factors, brain natriuretic peptide and blood lipid in CABG postoperative patients

Objective:To explore the effects of compound danshen dripping pills on the levels of serum inflammatory factors,brain natriuretic peptide(BNP)and blood lipid in CABG postoperative patients.Methods:156 cases of patients who were given CABG from January 2015 to January 2018 in Baogang Hospital were chosen and randomly divided into the observation group(n=78)and the control group(n=78).Both groups were given conventional drugs,simultaneously,the observation group was given compound danshen dripping pills.The treatment lasted 3 months.The clinical efficacy was compared between two groups of patients,and the levels of serum inflammatory factors,plasma BNP and blood lipid before and after treatment in two groups of patients were detected in order to make a comparison in the incidence of adverse cardiac events between two groups of patients.Results:After treatment,the total effective rate of treatment in the observation group was significantly higher than that in the control group;in the two groups,the levels of serum interleukin-6(IL-6),interleukin-8(IL-8),C-reactive protein and plasma BNP after treatment were obviously lower than those before treatment,and these indicators in the observation group were lower than those in the control group(p<.05);the levels of TG,TC and LDL-C in two groups were obviously lower(p<.05)with the level of HDL-C significantly higher(all p<.05),and the descending or ascending range of each indicator in the observation group was obviously larger than that in the control group(p<.05);in the follow-up visit,the incidence of adverse cardiac events in the observation group of patients was significantly lower than that in the control group of patients(p<.05).Conclusions:Compound danshen dripping pills can effectively reduce the levels of serum inflammatory factors and BNP,regulate blood lipid metabolism and reduce the incidence of adverse cardiac events in CABG postoperative patients.

Research survey and review of the effect of Compound Danshen Dripping Pills on the uric acid metabolism of patients with coronary heart disease

A growing number of studies have reported that serum uric acid（SUA） is associated with coronary heart disease（CHD）, which has been increasingly recognized and valued by the medical community. This paper surveys the epidemiological studies of hyperuricemia and CHD and summarizes the clinical study discussing the association between hyperuricemia and coronary heart disease with a prospect of exploring the possible mechanisms of compound Danshen dripping pills in reducing SUA in patients with coronary heart disease.

Simultaneous Determination of Four Ingredients in Guanxin Danshen Tablets by RP-HPLC

[Objectives]This study aimed to establish a method for simultaneous determination of four ingredients in Guanxin Danshen tablets by RP-HPLC.[Methods]HPLC chromatography was adopted with column of Thermo Hypersil-Keystone C 18 column(4.6 mm×250 mm,5μm),mobile phase of acetonitrile(A)-0.03 mol/L ammonium acetate(pH adjusted to 2.4 with formic acid)(B),gradient elution(0-5 min,5%A;5-10 min,5%A→19%A;10-40 min,19%A;40-68 min,19%A→36%A;68-90 min,36%A→95%A),flow rate of 1.0 mL/min and column temperature of 25℃.[Results]The content of salvianic acid A sodium,protocatechuic aldehyde,salvianolic acid B and tanshinone II A showed good linear relationship with chromatographic peak area in the range of 3.310-18.66,0.03950-0.2370,0.7500-4.500,0.05920-0.3550μg,respectively.The recovery rate(n=6)was 101.75%,96.86%,104.15%and 99.03%,respectively,and the RSD was 1.52%,2.81%,1.80%,and 1.37%respectively.The established method has good precision,reproducibility and stability.[Conclusions]This method can be used for the quality control of multiple ingredients of Guanxin Danshen tablets.

Compound Danshen Yeast 1.0

Background:Heterologous synthesis presents a promising new approach for accessing the active ingredients of traditional Chinese medicine(TCM),contributing to the conservation of natural medicinal resources.Compound Danshen preparation,a widely used TCM formulation,is designed to treat coronary heart disease and angina pectoris.It is primarily composed of Salviae Miltiorrhizae Radix et Rhizoma(Danshen),Notoginseng Radix et Rhizoma(Sanqi),and borneol(Bingpian).Danshen primarily yields tanshinones and phenolic acids,while Sanqi produces notoginsenosides.Borneol serves as an auxiliary agent to promote mental clarity,dissipate heat,and relieve pain.Objectives:The objective is to employ heterologous synthesis in a single yeast strain to produce the active ingredients of Compound Danshen preparation,and these include notoginsenosides,tanshinones,and borneol.Methods:Firstly,the“plug-and-play”terpene synthase screening framework in Saccharomyces cerevisiae was used for the identification of a novel,highly efficient bornyl diphosphate synthase.Furthermore,by leveraging the Compound Danshen preparation as a basis to concurrently reconstruct the biosynthetic pathways for the notoginsenoside precursor protopanaxadiol(a triterpene),the tanshinone precursor miltiradiene(a diterpene),and borneol(a monoterpene)within a single yeast strain.Results:This engineered strain,termed Compound Danshen Yeast 1.0,successfully produced protopanaxadiol at 62.34 mg/L,miltiradiene at 15.38 mg/L,and borneol at 2.54 mg/L in shake-flask fermentation.Conclusions:This research signifies the inaugural cross-species andmulticomponent synthetic biology endeavor that enables the synthesis of active ingredients in engineered cells,setting the stage for the industrial manufacture of TCM compounds.

Compound Danshen Dripping Pills combined with isosorbide mononitrate for angina pectoris: A systematic review and a Meta-analysis

Objective: To evaluate the efficacy of Compound Danshen Dripping Pills(CDDP) combined with isosorbide mononitrate(ISMN) versus ISMN alone for treating angina pectoris in patients.Methods: The Pub Med, Web of Science, Cochrane Library, Embase China National Knowledge Infrastructure, China Biomedical Literature Service System, Chinese Medical Journal Database, and Wan Fang MED databases were searched from inception to November 2022. Randomized controlled trials(RCTs) and cohort studies were included. The primary outcomes were angina symptom and electrocardiography(ECG) efficacy, angina symptom efficacy, and ECG efficacy. The protocol was registered with PROSPERO No. CRD42022314774.Results: Our study included 7 245 patients with angina(59 RCTs, 11 cohort studies). When ISMN was combined with CDDP, the efficacy of angina symptom and ECG [odds ratio(OR) = 4.824, 95% confidence interval(CI) = 3.636–6.401, P = 0.000], the efficacy of angina symptom(OR = 4.347, 95% CI = 3.635–5.198,P = 0.000), the efficacy of ECG(OR = 3.364, 95% CI = 2.767–4.089, P = 0.000) were better than that of patients treated with ISMN alone. CDDP combined with ISMN was superior to ISMN alone in reducing triglyceride(TG) [mean difference(MD) =-35.176, 95% CI =-37.439 to-32.912, P = 0.000], total cholesterol(TC)(MD =-24.296, 95% CI =-26.429 to-22.163, P = 0.000), the duration of angina attack(MD =-1.991, 95% CI =-2.349 to-1.633, P = 0.000), and the frequency of angina attack [standardized MD(SMD) =-2.840, 95% CI =-3.416 to-2.265, P = 0.000]. There was no increase in adverse events between CDDP combined with ISMN and ISMN alone(OR = 0.513, 95% CI = 0.421–0.626, P = 0.000).Conclusion: CDDP combined with ISMN improved treatment efficacy and was well tolerated. Therefore,this combination could be used as an alternative treatment. However, clinical and patient conditions should be considered.

Systematic review and Meta-analysis of 26 randomized controlled clinical trials of Compound Danshen Dripping Pill for non-proliferating diabetic retinopathy

Objective:Diabetic retinopathy(DR) is the retinal consequence of chronic progressive diabetic microvascular leakage and occlusion.Non-proliferating diabetic retinopathy(NPDR) is the early stage of DR.It eventually occurs to some degree in all patients with diabetes mellitus.In recent years,many clinical trials have shown that Compound Danshen Dripping Pill(CDDP) may be associated with the improvement of NPDR symptoms.The aim of this study was to quantitatively summarize the association between CDDP and the therapeutic effects of NPDR.Methods:It was conducted that a systematic literature search of Pub Med,Web of Science,CNKI,VIP and Wanfang Data updated in June 2020 with the following search terms:"diabetic retinopathy° or"retinopathy° or "DR° or "NPDR°,in combination with "Compound Danshen Dripping Pill° or "Salvia miltiorrhiza° or "Danshen°.Risk ratio(RR) and weighted mean difference(WMD) with their 95% confidence interval(CI) was calculated between treatment and control groups.The sensitivity analyses were undertaken by removing each individual study when high heterogeneity appeared.Subgroup analysis,Metaregression,and publication bias analysis were also conducted.The strength of evidence was evaluated with the Grading of Recommendation,Assessment,Development,and Evaluation(GRADE) method.Results:Twenty-six RCTs involving 2047 subjects were included to conduct a Meta-analysis after screening the studies,extracting the data,and assessing the study quality.The Stata15.0 software was utilized for processing.Meta-analysis indicated that curative effects of treatment group with CDDP was significantly better than control [RR = 0.54,95% CI(0.40,0.73);moderate-quality evidence].In addition,the results showed that CDDP was significantly associated with improving retinal hemorrhages[WMD =-0.62,95% CI(-0.78,-0.46);low-quality evidence],the vision [WMD = 0.14,and 95% CI(0.09,0.19),low-quality evidence],fundus fluorescence angiography [RR = 0.37 and 95% CI(0.23,0.60);low-quality evidence],reduction of retinal microaneurysm [WMD =-3.74 and 95% CI(-4.38,-3.11);moderate-quality evidence],hemangioma volume [WMD =-3.15,95%CI(-3.45,-2.85);moderate-quality evidence],macular thickness [WMD =-5.52,95%CI =(-64.27,-48.78);low-quality evidence],mean defect [WMD =-1.65 and 95% CI(-1.95,-1.34);very low-quality evidence],fasting blooding glucose [WMD =-0.95,95% CI(-1.19,-0.70);low-quality evidence),hemoglobin A1c[WMD =-0.62,95% CI(-0.93,-0.30);low-quality evidence],high sensitive C reaction protein[WMD =-5.66,95% CI(-8.01,-3.31);low-quality evidence].Sensitivity,subgroup,and Metaregression analyses were also assessed.Conclusion:The study demonstrated that CDDP has beneficial clinical effects for treating NPDR and improve the vision.Moreover,it indicated that oral CDDP in NPDR patients led to significant regulation of serum level of fasting blooding glucose,hemoglobin A1c and high sensitive C reaction protein,which was associated with the pathogenesis of NPDR.However,high-quality and large randomized clinical trials will be needed to prove the consequence in future.