Functional networks for Salvia miltiorrhiza and Panax notoginseng in combination explored with text mining and bioinformatical approach

Objective A large number of traditional Chinese medicine(TCM)are widely used for the treatment of patients with cerebral hemorrhage in China. The aim of this study is to systematically review the existing clinical evidences on TCM treatment for cerebral hemorrhage. Methods Randomized controlled trails(RCTs) of TCM treatment of cerebral hemorrhage were identified, eligible studies were included, the methodological quality of inclusive trails was assessed by the modified Jadad scale. The Cochrane Collaberation's Revman 5.20 was used for data analysis. Results 69 RCTs were available and included. Meta-analysis indicated that relative risk of overall effective rate of Sanqi, Ciwujia, Chuanxiongqin and Naoxueshu were significant difference; SMD(95% CI) of neural function defect score was SMD＝-0.46, 95% CI(-0.56, -0.35)of Sanqi, Danshen, Qingkailing, Liangxuetongyufang；SMD(95%CI) of the reduce of cerebral hemorrhage was SMD＝-0.98, 95% CI(-1.32, -0.63)of Danshen, Dahuang, Ciwujia, Qingkailing,Liangxue-Tongyufang. Conclusions The evidence currently available showed that the TCM which included do not increase the death rate and adverse reaction of the patients with cerebral hemorrhage, TCM could reduce neurological deficit and improve the absorption of hematoma． Key words: Cerebral hemorrhage; Traditional Chinese medicine; Randomized controlled trials; Systematically review; Death rate; Adverse reaction; Neurological deficit; Hematoma absorption

The herb pair comprising Salvia miltiorrhiza (SM) and Panax notoginseng (PN) has been used as a classical formula for cardiovascular diseases (CVDs) in China and in western countries. However, the pharmacology of SM and PN in this herb pair has not been fully elucidated. The aim of this study was to compare the mechanisms of SM and PN at the molecular level for the treatment of CVDs. We used a systems pharmacology approach, integrating ligand clustering, chemical space, docking simulation and network analysis, to investigate these two herbal medicines. The compounds in SM were attached to clusters 2, 3, 5, 6, 8 and 9, while the compounds in PN were attached to clusters 1, 2, 4, 5, 6, 7, 8 and 10. The distributions of chemical space between the compounds from SM and PN were discrete, with the existence of small portions of overlap, and the majority of the compounds did not violate ‘Lipinski’s rule of five’. Docking indicated that the average number of targets correlated with each compound in SM and PN were 5.0 and 3.6, respectively. The minority nodes in the SM and PN drug-target networks possessed common values of betweenness centrality, closeness centrality, topological coefficients and shortest path length. Furthermore, network analyses revealed that SM and PN exerted different modes of action between compounds and targets. These results suggest that the method of computational pharmacology is able to intuitively trace out the similarities and differences of two herbs and their interaction with targets from the molecular level, and that the combination of two herbs may extend their activities in different potential multidrug combination therapies for CVDs.

Development of an HPLC–UV–ELSD Method for Quantification of Multiple Components of a Chinese Medicine Made from Radix salvia miltiorrhiza and Panax notoginseng

Diabetic kidney disease (DKD) is one of the most common and severe chronic microvascular complications of diabetes mellitus (DM). The pathogenesis of DKD is complex, and lipid metabolism disorders play an important role in the pathogenesis of DKD. DKD belongs to the category of “kidney deficiency”, “edema”, “guan ge” and other pathological factors secondary to “thirst quenching disease” in traditional Chinese medicine. The pathological factors mainly focus on blood stasis and toxicity, which is consistent with modern medical theory. At present, the efficacy and safety of integrated traditional Chinese and Western medicine in treating lipid metabolism disorders in patients with DKD have been extensively studied and confirmed. In this review, the application and possible mechanism of traditional Chinese patent medicines (Bailing Capsule, Shenyan Kangfu Tablets, Jinshuibao Capsule, Huangkui Capsule, Yi-Shen-Hua-Shi granule, Shenmai injection), Chinese medicine compound (Tangshen Formula, Danggui Buxue Decoction, Tangshenkang), single Chinese medicine (Astragalus membranaceus, Panax notoginseng, Salvia miltiorrhiza) combined with Western medicine in the treatment of DKD with lipid metabolism disorder were discussed, in order to provide ideas for clinical diagnosis and treatment of patients with DKD with lipid metabolism disorder.

A narrative review of Panax notoginseng: Unique saponins and their pharmacological activities.

Proteomic method (two-dimensional electrophoresis and MS/MS) was used in studying the mechanisms of Traditional Chinese Medicines (TCMs) including Ganoderma lucidum, Salvia miltiorrhiza, Panax notoginseng and toad venom. For example, the effects of Salvia miltiorrhiza, a TCM popularly used for treating cardiovascular diseases, on the protein expression profiles of platelets, cardiomyocytes and heart tissues were checked. The results indicated that salvianolic acids from Salvia miltiorrhiza could inhibit the aggregation and adhesion of platelets, migration of cardiomyocytes and could protect cardiomyocytes from ischemia-reperfusion injury both in vitro and in vivo. The effects of salvianolic acids might be based on regulation of expression of proteins related to calcium ion binding, cell skeleton structure, elimination of reactive oxygen species, response to stress, etc. Furthermore, combined effects of salvianolic acids and notoginsengnosides, a TCM formula were also studied. The proteomic results showed that, in adjusting the un-normal protein expression profiles caused by ischemia-reperfusion injury back to normal, Fufang had better effect than either salvianolic acids or notoginsengnosides. Our results indicated the usefulness of proteomic technology in TCM research.

Objective To explore the effect of creatine phosphate combined with salvia miltiorrhiza polyphe-nols acid salt in treatment of coronary heart disease heart failure. Methods 114 cases of patients with coronary heart disease heart failure were selected as research objectives, who were treated in our hospital from August 2012 to August 2014. And they were randomly divided into control group(55 cases)and research group(59 cases)according to the number table method. Routine therapy of heart failure were given in both groups and the research group were added creatine phosphate combined with salvia miltiorrhiza polyphenols acid salt. The clinical efficacy of two groups of patients were observed and compared. Results The total effective rate in research group was 96.61%(57／59), significantly higher than 85.45%(47／55)in control group, the difference was statistically significant(χ2＝4.427,P＝0.035). Before treatment, the left ventricular ejection fraction(LVEF), left ventricular end diastolic diameter (LVEDD),left ventricular end systolic diameter(LVESD)and 6min walking distance between two groups had no sig-nificant difference(P＞0.05). After treatment, the LVEDD and LVESD of research group were decreased and LVEF and 6 minutes walking distance of two groups were increased, the difference was statistically significant(P＜0.05), the LVEDD and LVESD of research group were lower than that of the control group and LVEF and 6 minutes walking distance were higher than that of control group, the difference was statistically significant(P＜0.05). No complications or side effects related to the treatment were found in both groups. Conclusion On the basis of routine therapy of heart failure, the effect of creatine phosphate sodium combined with salvia miltiorrhiza polyphenols acid salt in treat-ment of coronary heart disease heart failure can improve cardiac function of the patients with the indicators, and the clinical effect is obvious,and side effects is rarely observed. Key words: Coronary heart disease heart failure; Salvia miltiorrhiza polyphenols acid salt; Creatine phosphate

Salvia miltiorrhiza and Panax notoginseng were both considered to be beneficial to cardiovascular diseases in traditional Chinese medicine and often used in combination. To examine the possible interaction between them, the effects of the active fractions of these two herbs, salvianolic acids (SA) and notoginsengnosides (NG), on platelet aggregation were checked respectively or in combination in vitro and in vivo. Both the platelet aggregation of platelet rich plasma (PRP) and washed platelet after ADP induction were checked. In vitro study showed that both SA and NG had an inhibitory effect on platelet aggregation. However, there is no synergistic effect of the combination of SA and NG in vitro. In vivo study showed that i.g. 550 mg/kg/day SA or NG for 5 days could significantly inhibit ADP-induced platelet aggregation of PRP. Moreover, combination of SA and NG at a ratio of 5:1 had a synergistic effect on platelet aggregation of PRP. The mechanism for the synergism of SA and NG in vivo was not clear. High performance liquid chromatography analysis of the plasma of rats received SA, NG or combination of SA and NG showed that co-administration of NG caused change in the plasma distribution profile of SA. The influence of combination on the absorption and/or metabolism of SA may be one of the reasons for the synergism of SA and NG in vivo.

Objective To explore the effects of salvia miltiorrhizae (SM) injection on the apoptosis of cultured rat neuronal stem cells induced by hypoxia and the activity of Caspase-3, in order to provide the further evidence for the molecular mechanism of neuroprotection of SM injection. Methods The neuronal stem cells from neonatal rat hippocampus were cultured and divided randomly into normal control group, hypoxia group and SM treatment group. After Hoechst staining, the apoptotic morphological change and apoptosis percentage were observed under fluorescence microscope. The activities of Caspase-3 in the 3 groups were evaluated by the colorimetric assay. Results Compared with normal control group [(2.75±0.28)%, 1.16±0.07], the percentage of apoptosis and the activity of Caspase-3 were increased significantly in neuronal stem cells cultured in hypoxia [(30.12%±2.09)%,3.85±0.41, P<0.05). Application of SM injection reduced markedly the percentage of apoptosis and the activity of Caspase-3 of the neuronal stem cells cultured in hypoxia [(9.16±1.34)%, 1.50±0.09, P<0.05].Conclusion SM injection can depress the apoptosis of the rat neuronal stem cells induced by hypoxia,so as to exert the neuroprotection. Key words: Salvia miltiorrhizae; Neuronal stem cells; Hypoxia; Apoptosis; Caspase-3

Objective To observe the efficacy of Panax notoginseng in promoting the absorption of chronic subdural hematoma in rabbits.Methods A stable pathological animal model similar to CSDH in humans was established using a small number of subdural injections of blood through a subdural pre-catheter in rabbits.Panax notoginseng powder was administrated by lavage for six days.The volume of subdural hematoma in each group was observed.The pathological features of the hematoma outer membranes were observed via hematoxylin and eosin staining.The ultrastructures of the outer membranes were observed with transmission electronic microscopy.The permeability of outer membrane and neovascularization were detected with lanthanum nitrate.Results The group administrated with Panax notoginseng powder had a significantly lower volume of residual subdural hematoma compared with the model group (P ＜ 0.01).The dura mater associated with hematomas showed reactive thickening in both groups.The inflammatory reaction and fibrous tissue proliferation in the hematoma outer membrane of Panax notoginseng group were less than the model group.The structure and function of new capillaries in the outer membrane of the model group were defected,which resulted in red blood cells escaping outside the vessel and lanthanum granules deposited in the extracellular space.However,in Panax notoginseng group,the new capillaries developed well,endothelial cells and basement membranes were integrated and connected closely,and less lanthanum granules were found in the extracellular space.Conclusions Panax notoginseng could effectively promote the absorption of subdural hematoma or fluid.This might have resulted from relieving inflammation and reducing new capillary permeation in the outer membrane of a hematoma capsule,which may accelerate the physiopathologic process and thus promote the recovery process from pathological states to normal. Key words: Chronic subdural hematoma; Panax notoginseng; Rabbit

BackgroundMyocardial infarction (MI) is one of the first cardiovascular diseases endangering human health. Inflammatory response plays a significant role in the pathophysiological process of MI. Messenger RNA (mRNA) has been proven to play a key role in cardiovascular diseases. Single-cell sequencing (SCS) technology is a new technology for high-throughput sequencing analysis of genome, transcriptome, and epigenome at the single-cell level, and it also plays an important role in the diagnosis and treatment of cardiovascular diseases. Machine learning algorithms have a wide scope of utilization in biomedicine and have demonstrated superior efficiency in clinical trials. However, few studies integrate these three methods to investigate the role of mRNA in MI. The aim of this study was to screen the expression of mRNA, investigate the function of mRNA, and provide an underlying scientific basis for the diagnosis of MI.MethodsIn total, four RNA microarray datasets of MI, namely, GSE66360, GSE97320, GSE60993, and GSE48060, were downloaded from the Gene Expression Omnibus database. The function analysis was carried out by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) enrichment analysis. At the same time, inflammation-related genes (IRGs) were acquired from the GeneCards database. Then, 52 co-DEGs were acquired from differentially expressed genes (DEGs) in differential analysis, IRGs, and genes from SCS, and they were used to construct a protein-protein interaction (PPI) network. Two machine learning algorithms, namely, (1) least absolute shrinkage and selection operator and (2) support vector machine recursive feature elimination, were used to filter the co-DEGs. Gene set enrichment analysis (GSEA) was performed to screen the hub-modulating signaling pathways associated with the hub genes. The results were validated in GSE97320, GSE60993, and GSE48060 datasets. The CIBERSORT algorithm was used to analyze 22 infiltrating immune cells in the MI and healthy control (CON) groups and to analyze the correlation between these immune cells. The Pymol software was used for molecular docking of hub DEGs and for potential treatment of MI drugs acquired from the COREMINE.ResultsA total of 126 DEGs were in the MI and CON groups. After screening two machine learning algorithms and key co-DEGs from a PPI network, two hub DEGs (i.e., IL1B and TLR2) were obtained. The diagnostic efficiency of IL1B, TLR2, and IL1B + TLR2 showed good discrimination in the four cohorts. GSEA showed that KEGG enriched by DEGs were mainly related to inflammation-mediated signaling pathways, and GO biological processes enriched by DEGs were linked to biological effects of various inflammatory cells. Immune analysis indicated that IL1B and TLR2 were correlated with various immune cells. Dan shen, san qi, feng mi, yuan can e, can sha, san qi ye, san qi hua, and cha shu gen were identified as the potential traditional Chinese medicine (TCM) for the treatment of MI. 7-hydroxyflavone (HF) had stable combinations with IL1B and TLR2, respectively.ConclusionThis study identified two hub DEGs (IL1B and TLR2) and illustrated its potential role in the diagnosis of MI to enhance our knowledge of the underlying molecular mechanism. Infiltrating immune cells played an important role in MI. TCM, especially HF, was a potential drug for the treatment of MI.

Objective To explore the changes of TXA2,PGI1 and hepatic function as well as effects of salvia miltiorrhiza on the patiente with server acute pancreatitis hepatic injury. Methods 57 patitnts with SAP were randomly divided ito control group and salvia miltiorrhiza treatment group. Patientes in control group received routine treatment, and the patients in salvia miltiorrhiza treatment group received additional salvia miltiorrhiza. The changes of plasma TXA2, PGI1 and hepatic function were conitored and compared between them. Results Plasma TXA2, the ratio of TXA2/PGI1 were significantly lower in the salvia miltiorrhiza group as compared with the control group on the 3,7,14 d after treatment( P ＜ 0.05 or P ＜ 0.01 ) ;but there were no obvious difference in the plasma PGI1 levels at each time point. The hepatic function in the salvia miltiorrhiza group were change normal after 14 days,which had signification difference than those in the control gruop P ＜ 0.05orP ＜0.01). Conclusion The salvia miltiorrhiza had a significant efficacy to treated the SAP hepatic injure. salvia miltiorrhiza may correct the imbalance between constrictionand factor and relaxation factor to improve the microcirculation of hepatic, and this was one of the mechanisms of salvia miltiorrhiza in treatment of SAP hepatic injure. Key words: Server acute pancreatitis; Hepatic injure; Salvia miltiorrhiza; TXA2/PGI1

Objective To investigate the effects of radix salvia miltiorrhizae on the apoptosis of hepatoeytes during cold preservation and reperfusion injury in rat donor liver. Methods Forty male SD rats were divided into experimental group, control group and sham operation group. The rat model of liver transplantation was established according to the Kamada method. The grafts were preserved in lactated Ringer's solution with radix salvia miltiorrhizae in experimental group and in lactated Ringer's solution in control group for 5 hours, then they were transplanted orthotopically. Six hours after transplantation, the recipients were sacrificed, and the serum ALT and AST were detected by automatic biochemistry analyzer, the hepatocyte apoptosis by TUNEL, the expression of Bcl-2 and FasL protein by flow cytometry. The histopathological changes of the liver grafts were observed under light microscope. Results The levels of ALT and AST in the experimental group were significantly lower than those in the control group after reperfusion. Compared with that in the control group, the apoptosis index of the hepatoeyte was signifieandy decreased in the experimental group ( F = 133.802, P 0.05). The histopathological injury of the liver grafts in the experimental group was significantly slighter than that in the control group. Conclusions Radix salvia mihiorrhizae inhibits the apoptosis of hepatocytes by increasing the Bcl-2 protein expression during cold preservation and reperfusion injury, so it has a protective effect on the liver graft against ischemia reperfusion injury. Key words: Radix salvia miltiorrhizae; Liver transplantation; Ischemia reperfusion injury; Cell apoptosis; Rat

Homocysteine (Hcy) is an independent risk factor for a variety of cardiovascular diseases, such as coronary heart disease, hypertension, stroke, etc. There is a close relationship between the vascular endothelial cell apoptosis and these diseases. Recent studies have shown homocysteine can induce apoptosis in endothelial cells, which may be an important mechanism for the development of theses cardiovascular diseases. Although there are several reports about how the Hcy induces apoptosis in endothelial cells, the exact mechanism is not fully understood. MicroRNAs are small, non-coding RNA. Previous studies have shown that there is a close relationship between several microRNAs and cell apoptosis. However, there are no studies about the role of microRNAs in Hcy-induced apoptosis in endothelial cells so far. In this study, we constructed the model of homocysteine-induced apoptosis in human coronary artery endothelial cells (HCAECs) and found miR-30b was significantly down-regulated by 1 mmol/L Hcy. In addition, overexpression of miR-30b can improve the Hcy-induced apoptosis in HCAECs by downregulating caspase-3 expression. Therefore, miR-30b may play an important role in Hcy-induced apoptosis in endothelial cells.

Objective To observate the effects of panax notoginseng saponin （PNS） on restenosis of rat vein graft. Methods Jugular vein-to-artery bypass grafting was performed on 30 Sprague-Dawley rats. The rats were divided into three groups： sham gruup, model group and PNS group. Drugs were administered at the second day after the operation for 14 days. The grafts were harvested for histoehemieal staining to observe the hyperplasia of neointima, and proliferating cell nuclear antigen （PCNA） expression, and apoptosis of smooth muscle cells were detected by TUNEL. Results In sham group, model group and PNS group, the endometrial thickness was （4. 05± 0. 85 ）, （26. 30 ±1.15 ）, （ 10. 80 ± 0. 98 ） p.m; the intima/media was （ 0. 22 ± 0. 09 ）, （ 0. 76 ± 0. 27 ）, （ 0. 45±0. 23 ）, respectively. The neointimal thickness in PNS group was significantly less than in model group （ P 〈 0. 05 ）. The PCNA expression in model group （A value） was （23.6± 4. 3 ）, significantly higher than in PNS group （ 11.5±3.6 ） （ P 〈 0. 05 ）. The percentage of apoptotic cells in model group was （4. 3 ± 1.9 ） , significantly lower than in PNS group （20. 3 ± 3.5 ） （ P 〈 0. 05 ）. Conclusion PNS can inhibit the neointimal hyperplais of vein graft, which can prevente restenosis after bypass grafts. Key words: Vein graft ; Panax notoginseng saponin ; Vascular restenosis ; Neointima