Umbilical Cord Mesenchymal Stem Cells Combined with Fufang Xueshuantong Capsule Attenuate Oxidative Stress and Vascular Lesions in Diabetic Rats by Activating Nrf-2/HO-1 Signaling Pathway.

BACKGROUND: Macrovascular lesions are the main cause of death and disability in diabetes mellitus, and excessive accumulation of cholesterol and lipids can lead to long-term and repeated damage of vascular endothelial cells. Umbilical cord mesenchymal stem cells (UCMSCs) can attenuate vascular endothelial damage in type 1 diabetic mice, while Fufang Xueshuantong capsule (FXC) has a protective effect on endothelial function; however, whether FXC in combination with UCMSCs can improve T2DM macrovascular lesions as well as its mechanism of action are not clear. Therefore, the aim of this study was to reveal the role of FXC + UCMSCs in T2DM vasculopathy and their potential mechanism in the treatment of T2DM. METHODS: The control and T2DM groups were intragastrically administered with equal amounts of saline, the UCMSCs group was injected with UCMSCs (1×106, resuspended cells with 0.5 mL PBS) in the tail vein, the FXC group was intragastrically administered with 0.58 g/kg FXC, and the UCMSCs + FXC group was injected with UCMSCs (1×106) in the tail vein, followed by FXC (0.58 g/kg), for 8 weeks. RESULTS: We found that FXC+UCMSCs effectively reduced lipid levels (TG, TC, and LDL-C) and ameliorated aortic lesions in T2DM rats. Meanwhile, Nrf2 and HO-1 expression were upregulated. We demonstrated that inhibition of Nrf-2 expression blocked the inhibitory effect of FXC+UCMSCs-CM on apoptosis and oxidative stress injury. CONCLUSION: Our data suggest that FXC+UCMSCs may attenuate oxidative stress injury and macroangiopathy in T2DM by activating the Nrf-2/HO-1 pathway.

Pharmacodynamic and targeted amino acid metabolomics researches on the improvement of diabetic retinopathy with Fufang Xueshuantong component compatibility.

The Fufang Xueshuantong capsule (FXT) has significant preventive and therapeutic effects on diabetic retinopathy(DR), but the compatibility of its active components remains to be thoroughly explored. In this study, a zebrafish diabetic retinopathy model was established using high-mixed sugars, and the optimal ratios of notoginseng total saponins, total salvianolic acid, astragaloside, and harpagide were selected through orthogonal experiments. Furthermore, we used UPLC-QqQ/MS to detect the changes in amino acid content of DR zebrafish tissues after administration of FXT and its compatible formula to analyze the effects of FXT and its compatible formula on amino acid metabolites. The results showed that the final compatibility ratios of the components were 8: 5: 1: 6.6 by comprehensive evaluation of the indicators. FXT and its compatibility formula had beneficial effects on retinal vasodilatation, lipid accumulation in the liver, total glucose, and VEGF levels in DR zebrafish, and all of them could call back some amino acid levels in DR zebrafish. In this research, we determined the compatible formulation of the active ingredients in the FXT and investigated their efficacy in DR zebrafish for further clinical applications.

Clinical observation of ticagrelor combined with Compound xueshuantong capsule in the treatment of unstable angina pectoris / 中国药房

OBJECTIVE To observe the efficacy and safety of ticagrelor combined with Compound xueshuantong capsules in the treatment of unstable angina pectoris. METHODS Totally 120 patients with unstable angina pectoris with deficiency of Qi and Yin combined admitted to Sanmenxia Hospital of Traditional Chinese Medicine from January 2021 to December 2022 were randomly divided into clopidogrel group （group A）， ticagrelor group （group B） and combined medication group （group C）， with 40 patients in each group. In addition to conventional treatment， group A was given clopidogrel orally； group B was given ticagrelor orally； group C was given ticagrelor and Compound xueshuantong capsule orally. After 12 weeks of treatment， the clinical efficacy， frequency of angina attacks， coagulation function indicators， cardiac function indicators， traditional Chinese medicine syndrome efficacy， and the incidence of adverse cardiovascular events and bleeding incidence were evaluated in the 3 groups. RESULTS The total effective rates of group A， group B and group C were 77.5%， 85.0% and 90.0%， respectively. The incidence of adverse cardiovascular events and bleeding events were 7.5%， 7.5% and 5.0% in the respective groups， with no statistically significant difference （P＞0.05）. The frequency of angina attacks， duration of angina attacks and duration of dyspnea were significantly reduced or shortened in all 3 groups after treatment compared to before treatment （P＜0.05）. The frequency of angina attacks in group C was significantly lower than that in groups A and B after treatment （P＜0.05）. The levels of fibrinogen （FBG） and D-dimer in all 3 groups were significantly lower after treatment compared to before treatment （P＜0.05）； group A had significantly higher levels of FBG and D-dimer compared to group B and C （P＜0.05）. The left ventricular end-diastolic diameter and left ventricular end-systolic diameter in all three groups were significantly shorter after treatment， and the left ventricular ejection fraction was significantly higher compared to before treatment （P＜0.05）， but there were no statistically significant differences among those groups （P＞0.05）. The total effective rates of traditional Chinese medicine syndrome efficacy in groups A， B and C were 67.5%， 80.0% and 87.5%， respectively， with group C being significantly higher than group A （P＜0.05）. CONCLUSIONS In addition to conventional treatment， ticagrelor combined with Compound xueguantong capsules can more significantly reduce the frequency of angina attacks in patients with unstable angina pectoris， reduce the levels of FBG and D- dimer， improve traditional Chinese medicine syndrome efficacy， and do not increase the risk of bleeding.

A review on the chemical profiles, quality control, pharmacokinetic and pharmacological properties of Fufang Xueshuantong Capsule.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Xueshuantong Capsule (FXC) is a traditional Chinese medicine (TCM) formula composed of four herbs including Panax notoginseng, Astragalus membranaceus, Salvia miltiorrhiza, and Scrophularia ningpoensis. Long-term and extensive clinical applications have confirmed that FXC could exert significant effects on fundus, cardiovascular and cerebrovascular occlusive diseases. AIM OF THE REVIEW: To systematically analyze and summarize the existing researches involving quality and efficacy re-evaluation of FXC, point out the typical problems, and further propose some opinions to contribute to future study. MATERIALS AND METHODS: Literatures concerning FXC were collected from online scientific databases including China National Knowledge Infrastructure, WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link up to June 2020. All eligible studies are analyzed and summarized in this review. RESULTS: This review outlines the chemical profiles, quality control, pharmacokinetic and pharmacological properties of FXC based on reported results. Some problems are pointed out for FXC: the quality control needs further improvement, the pharmacokinetic properties have not been comprehensively investigated, and in-depth and systematic mechanism researches are scarce. Hereon we propose several directions for future study: (a) establishment of feasible HPLC or LC-MS based quantitative methods for simultaneous determination of multiple components to monitor the overall quality; (b) pharmacokinetic studies concerning humans, drug-drug interactions, and correlation with pharmacodynamics; (c) pharmacological mechanism researches integrating multi-omics technologies (gut microbiome, metabolomics, etc.). CONCLUSIONS: This review highlights the researches on quality and efficacy re-evaluation of FXC, and points out some typical problems. Further in-depth studies should focus on the promotion of quality control, pharmacokinetic properties, and pharmacological mechanism.

Anti-thrombosis Effects and Mechanisms by Xueshuantong Capsule Under Different Flow Conditions.

Xueshuantong capsule (XST) is a patented traditional Chinese medicine used for the prevention and treatment of thrombosis. The molecular mechanism of anti-thrombotic effect of XST was investigated through the cross-talk among the platelets/leukocytes, endothelial cells (ECs), and flow shear stress. The Bioflux 1000 system was used to generate two levels of shear stress conditions: 0.1 and 0.9 Pa. Bioflux Metamorph microscopic imaging system was used to analyze the adhesion cell numbers. Protein expressions were detected by western blotting and flow cytometry. The flow-cytometry results showed that under 0.1 Pa flow, XST decreased ADP induced platelets CD62p surface expression in a concentration-dependent manner. Under 0.9 Pa flow, XST at a concentration of 0.15 g⋅L-1 reduced the platelets activation by 29.5%, and aspirin (ASA) showed no inhibitory effects. XST showed similar efficiency on monocytes adhesion both under 0.1 and 0.9 Pa flow conditions, and the inhibition rate was 30.2 and 28.3%, respectively. Under 0.9 Pa flow, the anti-adhesive effects of XST might be associated with the suppression of VE-cadherin and Cx43 in HUVECs. Blood flow not only acts as a drug transporter, but also exerts its effects to influence the pharmacodynamics of XST. Effects of XST on inhibiting platelets activation and suppressing platelets/leukocytes adhesion to injured ECs are not only concentration-dependent, but also shear stress-dependent. The mechanic forces combined with traditional Chinese medicine may be used as a precise treatment for cardiovascular diseases.

Curative effect evaluation of compound Xueshuantong capsule combined with calcium dobesilate for patients with early diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the clinical effect of compound Xueshuantong capsule combined with calcium dobesilate in the treatment for patients with early diabetic retinopathy ( DR) .?METHODS: According to the random table method, 54 cases of DR patients ( 68 eyes ) in the ophthalmological clinic of our hospital from February 2015 to November 2016 were divided into control group and research group with 27 cases (34 eyes) in each group. Patients in the control group were treated with calcium dobesilate tablets, while patients in the research group were treated with compound xueshuantong capsule based on the control group. The duration of treatment was 5mo in both groups. The total clinical efficiency of the two groups was calculated, and the visual, blood glucose and inflammatory factors of the two groups were detected before and after treatment, in addition the adverse reaction and recurrence rate were observed.?RESULTS:The total clinical efficiency of the patients in the research group was 91％ ( 31/34 ) , which was significantly higher than 68％ (23/34) of the control group (P<0. 05). Compared with before treatment, the vision, the volume of hemangioma, macular thickness, plaque area, grey value view, blood glucose and inflammatory factor levels of two groups of patients after treatment dropped significantly, meanwhile the vision, blood sugar and inflammation index levels of research group were better than control group, and the differences were statistically significant (P<0. 05). No adverse reactions occurred during the treatment of the two groups. The recurrence rate of research group was 3％ ( 1/31 ) , which was significantly lower than that of the control group as 26％ (6/23) (P=0. 039).? CONCLUSION: The curative effect of compound xueshuantong capsule combined with calcium dobesilate in the treatment of patients with early DR is significant. It can significantly improve eyesight, blood glucose and inflammatory response and has a good forward curative effect.

[Anti-platelet adhesive effect and mechanisms of Xueshuantong capsules under flow conditions].

To investigate the anti-platelet adhesive effect and possible mechanisms of Xueshuantong capsule (XST) under flow conditions. Human umbilical vein endothelial cells (HUVECs) and human platelets were employed as experimental materials, and TNF-α (20 µg•L⁻¹) was used to establish vascular endothelial cell injury models. In vivo flow conditions were simulated under controlled shear stress of 0.1 Pa and 0.9 Pa by Bioflux1000 assays accordingly. Anti-platelet adhesive effects of XST at 0.3 g•L⁻¹ were dynamically monitored by microscopic time-lapse photography. Western blotting was employed to detect the VCAM-1 expression on endothelial cells, and the release of 6-keto-PGF1α and TXB2 was tested by radioimmunoassay. The results showed that XST could inhibit the platelets adhesion under both physiological and pathological flow conditions, and the inhibition rate was 15.0% and 34.1% respectively. Under pathological low shear stress or static conditions, XST could significantly inhibit endothelial cells VCAM-1 expression and TXB2 release (P<0.05). These results suggested that XST inhibited platelets adhering to injured endothelium via decreasing VCAM-1 expression and TXA2 secretion from endothelium. From the interactions among blood flow, vascular endothelium and platelets, the anti-thrombosis effects of XST were possibly related to endothelial cells protection and therefore inhibiting platelets adhesion. Under different flow conditions, the antiplatelet adhesion effect of XST was different, and the pathological low shear stress was more conducive to the efficacy of XST.

Anti-platelet adhesive effect and mechanisms of Xueshuantong capsules under flow conditions / 中国中药杂志

To investigate the anti-platelet adhesive effect and possible mechanisms of Xueshuantong capsule (XST) under flow conditions. Human umbilical vein endothelial cells (HUVECs) and human platelets were employed as experimental materials, and TNF-α (20 μg•L⁻¹) was used to establish vascular endothelial cell injury models. In vivo flow conditions were simulated under controlled shear stress of 0.1 Pa and 0.9 Pa by Bioflux1000 assays accordingly. Anti-platelet adhesive effects of XST at 0.3 g•L⁻¹ were dynamically monitored by microscopic time-lapse photography. Western blotting was employed to detect the VCAM-1 expression on endothelial cells, and the release of 6-keto-PGF1α and TXB2 was tested by radioimmunoassay. The results showed that XST could inhibit the platelets adhesion under both physiological and pathological flow conditions, and the inhibition rate was 15.0% and 34.1% respectively. Under pathological low shear stress or static conditions, XST could significantly inhibit endothelial cells VCAM-1 expression and TXB2 release (P<0.05). These results suggested that XST inhibited platelets adhering to injured endothelium via decreasing VCAM-1 expression and TXA2 secretion from endothelium. From the interactions among blood flow, vascular endothelium and platelets, the anti-thrombosis effects of XST were possibly related to endothelial cells protection and therefore inhibiting platelets adhesion. Under different flow conditions, the antiplatelet adhesion effect of XST was different, and the pathological low shear stress was more conducive to the efficacy of XST.

Application of Fufang Xueshuantong capsule in patients with optic atrophy of glaucoma and its influence on ocular hemodynamics / 中国生化药物杂志

Objective To analyze the effect of Fufang Xueshuantong capsule on glaucomatous optic atrophy and its influence on ocular hemodynamics.Methods 124 cases of patients with glaucomatous optic atrophy from April 2014 to December 2016 in our hospital were selected,and randomly divided into experimental group and control group according to the order of hospital admission , with 62 cases in each group.The control group was treated with nerve growth factor plus vitamin needling,the experimental group was treated with nerve growth factor and vitamin and compound Xueshuantong capsule.Observation and comparison the total effective rate, visual function (visual acuity, total gray value) improvement of the two groups of patients, as well as the changes of ocular hemodynamic parameters (systolic peak velocity, diastolic End-stage blood flow velocity, resistance index, pulsatility index).Results The total effective rate of the experimental group was 93.55%(58/62), the total effective rate of the control group was 70.97%(44/62), the total effective rate of the experimental group was higher than the control group (P <0.05)).After treatment, the visual acuity of the experimental group was significantly higher than the control group, the total gray value of the experimental group was significantly lower than the control group (P<0.05).The peak systolic velocity and end diastolic velocity in the experimental group were significantly higher than those in the control group (P<0.05).The resistance index and pulsatility index in the experimental group were lower than those in the control group (P<0.05). Conclusion Compound Xueshuantong capsule is effective in the treatment of glaucomatous optic atrophy , can improve the ocular hemodynamics and improve the visual function.

Clinical efficacy of compound thrombosis capsule combined with compound anisodine injection in the treatment of non-proliferative diabetic retinopathy / 中国生化药物杂志

Objective To explore the clinical efficacy of compound Xueshuantong capsule combined with compound anisodine injection in the treatment of non-proliferative diabetic retinopathy.MethodsSixty patients with non-proliferative diabetic retinopathy were enrolled in this study.All patients were enrolled from March 2014 to May 2016 and were divided into two groups by simple randomization.The control group were treated with salvia miltiorrhiza injection, and the patients were treated with compound Xueshuantong capsule combined with compound anisodine injection.The clinical efficacy and the level of hemorheology were compared.ResultsThe clinical improvement rate was 93.33% in the observation group, which was significantly higher than that in the control group (P<0.05).The PV, HCT, KAI and Fg levels in the observation group were significantly lower than those in the control group (P<0.05).ConclusionCompound Xueshuantong Capsule combined with compound anisodine injection for local injection of non-proliferative diabetic retinopathy has a significant clinical effect and is widely used.

Efficacy evaluation of compound Xueshuantong capsule combined with calcium dobesilate in patients with early diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the effect of compound Xueshuantong capsule combined with calcium dobesilate in patients with early diabetic retinopathy.METHODS:Totally 120 patients with early diabetic retinopathy were selected,and they were randomly divided into study group and control group according to the random number table method,each had 60 cases.Patients in the control group were treated with compound Xueshuantong capsule,and the patients in the study group were treated with compound Xueshuantong capsule combined with calcium dobesilate.We observed and compared the clinical symptoms (hemangioma volume,hemorrhagic spot area,macular thickness,visual gray value,visual acuity,threshold sensitivity within 30°),inflammatory factors (serum hs-CRP,VEGF,IGF-1),clinical efficacy and adverse events.RESULTS:(1) The hematoma volume,hemorrhage spot area,macular thickness and visual gray value of the two groups were lower than those before treatment (tstudy group =24.81,19.59,8.567,17.79,tcontrol group =12.02,8.60,10.32,10.85;P＜0.05);visual acuity,threshold sensitivity within 30°were significantly higher than before (tstudygroup =-5.24,-8.79,tstudy group =-2.26,-3.39;all P＜0.05).After treatment,hemangioma volume,haemorrhagic area,macular thickness and visual gray value of the study group were lower than those of the control group,visual acuity and threshold sensitivity within 30°were higher than those of the control group (t=-12.97,-9.47,-13.54,-5.59,2.65,4.05;all P＜0.05).(2) The levels of hs-CRP,VEGF and IGF-1 in the two groups were lower than those before treatment (tstudy group =34.30,23.33,42.118,tcontrol group =18.68,17.46,26.73;all P＜0.05).The levels of hs-CRP,VEGF and IGF-1 in the study group were significantly lower than those in the control group (t=-14.79,-7.43,-15.35,all P＜0.05).(3)The total effective rate was 92.0％ in the study group,which was higher than 70.8％ in the control group (x2 =16.352,P＜0.05).(4) The incidence of adverse reactions was 10％ in the study group and 13％ in the control group.There was no significant difference in the incidence of adverse reactions between the two groups (x2 =0.32,P＞0.05).CONCLUSION:Compound Xueshuantong capsule combined with calcium dobesilate in the treatment of early diabetic retinopathy can effectively improve the clinical symptoms of retinal defects,the mechanism of action is related to the level of inflammatory factors,the clinical efficacy is better,security is high.

[Distribution of chemical compounds of Fufang Xueshuantong capsule in eyes and kidney of beagle dogs].

Diabetic retinopathy(DR) and diabetic nephropathy(DN) are the most common complications of diabetes, and the main causes of death and disability of diabetes. Clinical reports showed that Fufang Xueshuantong capsule(FXT) had effective curative effect on DR and DN, but there was no report on the distribution of chemical compounds of FXT in beagle dog eyes and kidneys. In this study, FXT was given by gavage administration in Beagle dogs for 3 days, and then their eyeballs and kidneys were taken. The chemical compounds in beagle dog eyes and kidneys were detected by HPLC LTQ-Orbitrap technology. Furthermore, by comparing with the data from retrieving literature and references, the chemical compounds were identified by the accurate mass, retention time (tR), and MS/MS. Fourteen and 19 types of notoginsenosides were respectively identified in eyeballs and kidneys in this study, and these results could lay foundation for clarifying the effective ingredients of FXT in treatment of DR and DN.

A combination of the main constituents of Fufang Xueshuantong Capsules shows protective effects against streptozotocin-induced retinal lesions in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Xueshuantong Capsule, an herbal formula licensed for clinical use in China, which is composed of Panax notoginseng (Burkill) F.H. Chen, Salvia miltiorrhiza Bunge, Astragalus membranaceus (Fisch.) Bunge, and Scrophularia ningpoensis Hemsl, has proven effective for the treatment of diabetic retinopathy. However, its bioactive constituents are still ambiguous. In this study, the therapeutic effects of a combination of the main constituents of Fufang Xueshuantong Capsule (cFXT) were evaluated in streptozotocin (STZ)-induced retinal lesions to identify the bioactive constituents. METHODS: Sprague-Dawley rats, except for those in the control group (vehicle+vehicle), were administered a single injection of 60mg/kg STZ. One-week later, STZ-treated rats were randomly divided into three groups-one STZ group (STZ+vehicle) and two cFXT treatment groups (STZ+cFXT). The rats in the latter two groups received cFXT 44.8mg/kg or cFXT 22.4mg/kg by intragastric gavage once per day, for 24 consecutive weeks. The rats in the control and STZ groups received the vehicle in the same way. Body weights and fasting blood glucose levels were recorded every four weeks. After treatment, hemorheological tests were performed to record the erythrocyte aggregation indexes, blood viscosity, and plasma viscosity. The trypsin digestion method was used to observe pericyte and acellular capillary counts in the retina. Ultraviolet spectrophotometry was utilized to measure the activity of aldose reductase (AR) by measuring the nicotinamide adenine dinucleotide phosphate (NADPH) consumption at 340nm. An immunohistochemical assay was used to observe the expressions of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the retina. The expression levels of intercellular adhesion molecule-1 (ICAM-1), endothelin-1 (RT-1),and occludin in the retina were tested by the western blot assay. RESULTS: cFXT is composed of 991.44mg/g saponins of Panax notoginseng, 1.62mg/g harpagoside, 0.70mg/g cryptotanshinone, 0.74mg/g tanshinone I, and 5.50mg/g astragaloside A. Although it showed no effects on the increased body weight and blood glucose levels induced by STZ in rats. However, it showed a tendency to attenuate the increase in erythrocyte aggregation, plasma viscosity, and acellular vessel and pericyte loss, paralleled with a reversal of the hyper-activation of AR, the hyper-expression of VEGF, ICAM-1, and ET-1, and the hypo-expression of PEDF and occludin in the retinas of STZ-treated rats. CONCLUSION: The saponins of Panax notoginseng, harpagoside, cryptotanshinone, tanshinone I, and astragaloside A are the main bioactive constituents of Fufang Xueshuantong Capsule and contribute to the attenuation of STZ-induced retinal lesions in rats. These constituents can be used as the base to optimize a new drug for the treatment of diabetic retinopathy, and can be selected for quality control of Fufang Xueshuantong Capsules.

Distribution of chemical compounds of Fufang Xueshuantong capsule in eyes and kidney of beagle dogs / 中国中药杂志

Diabetic retinopathy(DR) and diabetic nephropathy(DN) are the most common complications of diabetes, and the main causes of death and disability of diabetes. Clinical reports showed that Fufang Xueshuantong capsule(FXT) had effective curative effect on DR and DN, but there was no report on the distribution of chemical compounds of FXT in beagle dog eyes and kidneys. In this study, FXT was given by gavage administration in Beagle dogs for 3 days, and then their eyeballs and kidneys were taken. The chemical compounds in beagle dog eyes and kidneys were detected by HPLC LTQ-Orbitrap technology. Furthermore, by comparing with the data from retrieving literature and references, the chemical compounds were identified by the accurate mass, retention time (tR), and MS/MS. Fourteen and 19 types of notoginsenosides were respectively identified in eyeballs and kidneys in this study, and these results could lay foundation for clarifying the effective ingredients of FXT in treatment of DR and DN.

Study on effect of Fufang Xueshuantong capsule on serpine1,α-serpine1 protein and KLF2 in patients with lower extremity venous thrombosis / 中国生化药物杂志

Objective To explore the effect of serpine1, α-serpine1 protein and KLF2 in patients with lower extremity venous thrombosis by Fufang Xueshuantong capsule.Methods 44 patients were diagnosed with lower extremity venous thrombosis were collected, and randomly divided into experimental group and control group, 22 cases in each group, giving the conventional antiplatelet therapy, on the basis of this, the experimental group was given Fufang Xueshuantong capsule 1.5 g, three times a day orally, and the control group was given context Shutong granules 20 g, three times a day orally.2 weeks for a course of treatment, three courses of treatment.Before and after treatment in the detection of two groups of patients with serum serpine1, α-serpine1 KLF2 and protein contents, blood rheology, coagulation function, and carries on the analysis.ResuIts Compared with the control group, experimental group patients has better curative effect, the performance of: serum serpine1and α-serpine1 protein content were significantly decreased(P<0.05).KLF2 expression was significantly higher (P<0.05).Blood viscosity, erythrocyte aggregation index, erythrocyte sedimentation rate decreased significantly (P<0.05).Fib, D-D content significantly decreased (P<0.05).ConcIusions Fufang Xueshuantong capsule can reduce serum serpine1, α-serpine1 protein content and promote KLF2 expression, decrease the blood viscosity, erythrocyte sedimentation rate, improve patients with hypercoagulable state in patients with lower extremity venous thrombosis, so as to achieve good clinical efficacy.

Network pharmacology analyses of the antithrombotic pharmacological mechanism of Fufang Xueshuantong Capsule with experimental support using disseminated intravascular coagulation rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Xueshuantong (FXST) Capsule is developed on a traditional Chinese medicine remedy, with a four-herb formula of Panax notoginseng, Radix astragali, Salvia miltiorrhizae and Radix scrophulariaceae. It has been used for treatment of the clinic cardiovascular disease for many years. MATERIALS AND METHODS: Due to its complexity of compositions and polypharmacological effects, it often complicates understanding of the mechanisms of action. In the present work, we have constructed an integrated model of system pharmacology to investigate the polypharmacological mechanisms of FXST formulation for treatment of thrombosis disease. RESULTS: The predicted results showed that 22 ingredients in FXST were closely associated with 41 protein targets related to blood coagulation, fibrinolysis and platelet aggregation. Through analysis of the compound-protein target association, significant cross-targets between each herb indicated the multiple active chemical ingredients might interact with the same target simultaneously and thus explained the synergistic mechanisms of the principle of Traditional Chinese medicines (TCMs) as ''Jun (emperor) - Chen (minister) - Zuo (adjuvant) - Shi (courier)''. To validate the polypharmacological effects predicted by our network pharmacology (NetPharm) analysis, we have carried out experimental investigation the effects of FXST on the disorders of the blood coagulation system in a lipopolysaccharide-induced disseminated intravascular coagulation (DIC) rat model. The results showed that FXST could significantly ameliorate the activation of coagulation system, which is congruent with the cross-target prediction by NetPharm approach. CONCLUSIONS: The combined investigations provide more insight into better understanding of the pharmacological mechanisms of FXST, and may also offer an alternative avenue to further explore the chemical and pharmacological basis of TCMs.

Chinese medicinal formula Fufang Xueshuantong capsule could inhibit the activity of angiotensin converting enzyme.

Fufang Xueshuantong (FXST) capsule, a Chinese medicinal formula composed of four herbals - Panax notoginseng, Radix Astragali, Radix Salvia Miltiorrhizae and Radix Scrophulariaceae, has been used to treat cardiovascular diseases for many years, but the pharmacological mechanisms underlying its effects has not been clarified. This study investigates if a connection between FXST and angiotensin converting enzyme (ACE) might be an explanation for its pharmacological effects. ACE inhibition assay was performed on FXST capsule, 50% ethanol extracts from the four herbals and three selected saponins most abundant in P. notoginseng (Ginsenoside Rg1, Ginsenoside Rb1 and Notoginsenoside R1) using a biochemical test. Reversed-phase high-performance liquid chromatography of liberated hippuric acid from the ACE assay was conducted to determine the inhibitory effect. As a result, FXST and extracts from P. notoginseng showed a significant and dose-dependent inhibition on ACE activity with the IC50 values of 115 µg/ml and 179 µg/ml, respectively. But extracts from the other three herbals and the three selected saponins had no significant effect on ACE inhibition. Compared to other reported plant extracts, FXST could be considered as an effective ACE inhibitor. The inhibition of ACE activity supports the traditional use of FXST on blood circulation and the inhibitory property of FXST is mainly caused by P. notoginseng.

Application of quantitative analysis of multi-components by single-marker in detection of eight components of Fufang Xueshuantong capsule / 国际药学研究杂志

Objective: To set up a new method - quantitative analysis of multi-components by single-marker(QAMS) to determine eight components - notoginsenoside R1, ginsenoside Rg1, Re, Rb1 and Rd, harpagoside, cryptotanshinone and tanshinone I in Fufang Xueshuantong(FX) capsule simultaneously, and validate its accuracy and feasibility for application in preparation. Methods: FX capsule was used as the research object, notoginsenoside R1 was selected as marker under 203 nm to evaluate the quality of ginsenoside Rg1, Re and Rb1, Rd, and cryptotanshinone as marker under 270 nm to evaluate the quality of harpagoside and tanshinone I. The relative correction factors (RCF) of components were calculated. The method was validated by comparison of the quantitative results between external standard method and QAMS method. Results: No significant differences were found in the quantitative analysis of components by external standard method and QAMS method. Conclusion: It is a convenient and accurate method to determine multi-components when authentic standard substances are not available. It can be used to control the quality of FX capsule.

Simultaneous Determination of Eight Effective Compounds of Fufang Xueshuantong ;Capsule in Rat Plasma by LC-MS/MS / 中国中医药信息杂志

Objective To establish a sensitive and specific LC-MS/MS method for measurement of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd, tanshinone Ⅰ, astragaloside Ⅳ and harpagosidein of Fufang Xueshuantong Capsule in rat plasma. Methods The HPLC separation was performed on Thermo Hypersil GOLD column (2.1 mm× 100mm, 5 μm) at 30 ℃, injecting 10 μL and using acetonitrile-water (0.1% formic acid) as the mobile phrase (B was acetonitrile, A was 0.1%formic acid;0-10 min, 25%-55%B;10-20 min, 55%-70%B) with the flow rate of 0.2 mL/min. Detection was performed on a tandem quadrapole mass spectrometer using positive electrospray ionization, SRM scan mode. Results The eight compounds showed good linearity in wide ranges (notoginsenoside R1 1.00-800 ng/mL, ginsenoside Rg1 0.950-760 ng/mL, ginsenoside Re 1.44-1440 ng/mL, ginsenoside Rb1 1.33-1330 ng/mL, ginsenoside Rd 9.90-990 ng/mL, harpagosidein 1.01-1010 ng/mL, astragaloside Ⅳ 1.16-928 ng/mL, tanshinone Ⅰ 10.0-800 ng/mL). In addition, the accuracy and recovery were around 85%-115%and 50%-70%. The RSD of intra and inter day precision were lower than 15%. Conclusion The method is specific, rapid and sensitive. Therefore, it can be applied to pharmacokinetic study of eight effective compounds in Fufang Xueshuantong Capsule.

Retinal hemodynamic influence of compound xueshuantong capsule on nonproliferative diabetic retinopathy after laser photocoagulation / 国际眼科杂志(Guoji Yanke Zazhi)

AlM: To observe retinal hemodynamic influence of compound xueshuantong capsule on nonproliferative diabetic retinopathy ( NPDR) after laser photocoagulation.METHODS:A total of 41 patients (72 eyes) with NPDR after laser photocoagulation were enrolled in this study. They were all given compound xueshuantong capsule, and used color Doppler flow imaging for detection of retinal hemodynamics. RESULTS: After treatment, patients with retinal blood perfusion significantly improved; central retinal arterial peak systolic velocity ( PSV ) , end - diastolic velocity (EDV) and medial velocity (Vm) were increased, while the resistance index ( Rl) decreased. The difference have statistical significance (P CONCLUSlON: Compound xueshuantong capsule can improve retinal blood perfusion for nonproliferative diabetic retinopathy after laser photocoagulation, which is related to improvement of visual prognosis.