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ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg-1·d-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg-1·d-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.
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Objective@#To investigate the clinical effect of Honghua Xiaoyao granule combined with tamoxifen citrate tablets in the treatment of polycystic ovary syndrome (PCOS).@*Methods@#From June 2017 to January 2019, 92 patients with PCOS admitted to Chengde maternal and child health care hospital were selected as the study objects, and divided into control group (46 cases) and treatment group (46 cases) according to the order of admission.The patients in the control group took tamoxifen citrate tablets, 2 tablets/time, 1 time/day from the 5th day of menstrual cycle.The patients in the treatment group were treated with safflower Xiaoyao granules on the basis of tamoxifen citrate tablets, 3 bags/time, 3 times/day.After 21 days of continuous administration, 5 days of discontinuation was a course of treatment, and the two groups of patients were treated for 3 consecutive courses.The clinical effect, ovulation, blood glucose, insulin resistance index, sex hormone level and oxidative stress of the two groups were compared before and after treatment.@*Results@#The total effective rate of the treatment group was 95.65% (44/46), the ovulation rate was 97.83% (45/46), the control group was 80.43% (37/46), 84.78% (39/46), the difference between the two groups was statistically significant (χ2 value was 5.06, 4.93, P value was 0.025, 0.029). .Before and after treatment, the fasting insulin were (20.31±3.06) mU/L and (12.49±2.34) mU/L, and the homeostatic model assessment of insulin resistance were 4.84±1.30 and 2.92±0.83 in the treatment group, which were (20.14±2.55) mU/L, (16.15±2.17) mU/L, 4.86±1.08 and 3.86±0.93 in control group.There all were differences in two groups about the insulin resistance index before and after treatment, and there all were differences between two groups about the insulin resistance index after treatment (tvalue was 26.15 , 16.10, 19.68 and 12.17; all P<0.001). and there were statistically significant differences between the two indexes after treatment (t=0.77, 5.11, all P<0.001). Before and after treatment, the luteinizing hormone were (19.98±2.22) and (12.61±2.55) U/L, and the follicle stimulating hormone were (5.97±0.69) U/L and (4.52±0.79) U/L, and testosterone was (5.38±0.88) and (3.62±0.60) nmol/L, which was (20.44±2.23) U/L, (16.18±2.65) U/L, (6.09±0.59) U/L, (5.31±0.86) U/L, (5.44±0.77) nmol/L and (4.48±0.62) nmol/L in control group.The difference between the two groups before and after treatment was statistically significant (t value was 23.32, 15.29, 13.70, 8.67, 19.80 and 12.30, respectively; all P<0.001); and the difference between the groups after treatment was statistically significant (t value was 6.58, 4.61 and 6.70, respectively, all P<0.001). Before and after treatment, the malondialdehyde were (9.20±1.15) μmol/L and (5.63±0.94) μmol/L, and the superoxide dismutase were (62.99±5.37) U/L and (89.63±8.81) U/L, which were (9.45±1.08) μmol/L, (7.48±0.85) μmol/L, (61.88±5.78) U/L and (75.60±6.87) U/L in control group.There all were differences in two groups about the oxidative stress index before and after treatment, and there all were differences between two groups about the oxidative stress index after treatment (t value was 40.00, 19.84, 28.14, 15.24, 9.88 and 8.52, respectively, all P<0.001).@*Conclusion@#Honghua Xiaoyao Granules combined with Tamoxifen Citrate Tablets can effectively improved the clinical symptoms of patients with PCOS, promoting ovulation, reducing sex hormone level, improving insulin resistance and oxidative stress, which has a certain clinical application value.
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Aim To establish a method for determining the antithrombotic biological activity of Honghua injection, which can be used to evaluate and control its quality. Methods Collagen-adrenalin was used to induce mouse acute cerebral thrombosis model and hemiplegic protection rate of Honghua injection in mice as an index to investigate the antithrombotic activity of Honghua injection. The experimental conditions of the administration dosage, inducer dosage, and different strains of mice were investigated, and the experimental conditions were optimized by orthogonal design. Results Honghua injection which was made by 5. 0 g crude drug · kg-1and continuously ip for 3 d, had obvious protective effect on collagen-adrenalin-induced acute cerebral thrombosis in mice. The established biological activity limit method showed a good repeatability, intermediate precision, and reproducibility. Each sample showed different degrees of differences in biological activity. Conclusions The thrombus test in mice can be used as a method for measuring the biological activity of Honghua injection. It is recommended to use 5. 0 g crude drug · kg-1dose as the limit for bioactive process optimization and product quality controlment of Honghua injection.
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Objective: To explore the molecular mechanism of Taoren-Honghua herb pair (THP) on syndrome of bloodstasis based on the network pharmacology. Methods: We collected THP's compounds from traditional Chinese Medicinedatabases and input them into Pharm Mapper to get their potential targets, and collected the known targets of compoundsby Scifinder. Then we did KEGG-pathway analysis by DAVID database. Finally draw and analyze the network byCytoscape by information above. Results: Seventeen compounds of THP acquired 74 known targets, which was associatedwith four modules: improving the hemodynamics, anticoagulation, anti-inflammation, regulating apoptosis andproliferation. We also got 317 potential targets through PharmMapper and got 128 signaling pathway through pathwayenrichment including 39 disease-related pathways, 25 endocrine-related pathways, 11 immune-related pathways and soon. Conclusion: The four modules of the known target are exactly related to the four characteristics of the syndrome ofblood stasis. The potential targets and the 128 signal pathways involve a variety of pathophysiological processes of thesyndrome of blood stasis. These reflect the molecular mechanism of THP intervention in the syndrome of blood stasis
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To evaluate the promoting blood circulation and removing blood stasis effects of Danshen-Honghua(DH) herb pair with different preparations (alcohol, 50% alcohol and water) on blood rheology and coagulation functions in acute blood stasis rats, and optimize the best preparation method of DH based on principal component analysis(PCA), hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods. Ice water bath and subcutaneous injection of adrenaline were both used to establish the acute blood stasis rat model. Then the blood stasis rats were administrated intragastrically with DH (alcohol, 50% alcohol and water) extracts. The whole blood viscosity(WBV), plasma viscosity(PV), erythrocyte sedimentation rate(ESR) and haematocrit(HCT) were tested to observe the effects of DH herb pair with different preparations and doses on hemorheology of blood stasis rats; the activated partial thromboplastin time(APTT), thrombin time(TT), prothrombin time(PT), and plasma fibrinogen(FIB) were tested to observe the effects of DH herb pair with different preparations on blood coagulation function and platelet aggregation of blood stasis rats. Then PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods were all used to comprehensively evaluate the total promoting blood circulation and removing blood stasis effects of DH herb pair with different preparations. The hemorheological indexes and coagulation parameters of model group had significant differences with normal blank group. As compared with the model group, the DH herb pair with different preparations at low, middle and high doses could improve the blood hemorheology indexes and coagulation parameters in acute blood stasis rats with dose-effect relation. Based on the PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods, the high dose group of 50% alcohol extract had the best effect of promoting blood circulation and removing blood stasis. Under the same dose but different preparations, 50% alcohol DH could obviously improve the hemorheology and blood coagulation function in acute blood stasis rats. These results suggested that DH herb pair with different preparations could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats, and the optimized preparation of DH herb pair on promoting blood effects was 50% alcohol extract, providing scientific basis for more effective application of the DH herb pair in modern clinic medicine.
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Herb pairs are usual clinical compatibility forms and one of compound prescription sources in Chinese medicine. Pharmacokinetic research in vivo is one of the important items in elucidating the mechanism for synergistic and attenuated mechanisms of herb pairs. The paper comprehensively summarized and systemized the pharmacokinetic researches of marker-ingredients about Danshen-Honghua and Danshen-Bingpian in order to elucidate the rationality and scientificity of herb pairs and provide some feasible suggestions on the pharmacokinetics of drugs in the future. In view of complicated system of Traditional Chinese medicines and a chemical system that is not separated from its natural state, comparative pharmacokinetic researches on marker-ingredients from the herb pairs are reasonable to elucidate the synergistic and attenuated mechanisms of monarch-subjects compatible herbs and monarch-guide compatible herbs. Such pharmacokinetic research can better explain the mechanism of drug compatibility, while the pharmacokinetic researches based on the monomer chemical compositions and marker-ingredients that have been separated from complex chemical environment of traditional Chinese Medicine are still unreasonable and should be discussed deeply.
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Objective: To establish an optimization model for the extraction technology process of Honghua Tongluo Prescription (HTP) based on fuzzy analytic hierarchy process (FAHP). Methods: The evaluation indexes tree was established which included objective level, criterion level, and index level. The criterion level consisted of effective constituent, impurity control, behavioristics, histopathology, and immune response. The index level consisted the extraction efficiency of hydroxysafflor yellow A (HSYA) and icariin, the content of total substances, mechano-allodynia, and mechano-hyperalgesia, the ratios of decentered nucleolus in dorsal root ganglion, the content of SP in pelma skin with plantar P quality as the index layer. Weighting coefficient of all the indexes was decided by FAHP based calculation. HTP extraction process route was comprehensively evaluated. Results: The importance degrees (ω) of each criterion from high to low were: immune response (ω=0.245), histopathology (ω=0.23), effective constituent, behavioristics (ω=0.20), and impurity control (ω=0.125). The optimized extraction technology process was that Carthami Flos was better extracted by warm maceration with water at 60℃, Epimedii Herba was circulated by reflux extraction with water. Cinnamomi Ramulus was better treated by reflux extraction with 80% alcohol. Conclusion: An FAHP-based evaluation method with pharmacological indexes, effective constituent indexes, and impurity control as evaluation indexes, which could put formula Chinese materia medica principle and modern pharmaceutical engineering demands into consideration, is comprehensive and effective.
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Objective To investigate the clinical effect of honghua injection on hemorrheology in the prevention of deep venous thrombosis ( DVT) after operation of lower limbs fractures.Methods 100 cases with operation of lower limb fracture meeting the inclusion critera were randomly divided into two groups equally.Besides conventional treatment, the control group was treated with rivaroxaban, while the observation group was treated with honghua injection and rivaroxaban.The incidence of DVT, pro-inflammatory factors, hemorheology indices and adverse reactions were observed and compared. Results The observation group had a total DVT incidence of 10.0%, which was statistically lower than that of 28.0% in the control group(P<0.05). Three days after the operation, pro-inflammatory factors of TNF-α, IL-6 and IL-8 in the observation group was respectively statistically lower than that in the control group(P<0.05).As to hemorheology indices, in comparison with the control group, hematocrit, whole blood viscosity and fibrinogen in the observation group were statistically lower (P<0.05).During the treatment, there were no case of severe adverse reactions, and the incidence of adverse reactions in the two groups were statistically same.Conclusion Treatment of honghua injection in combination with rivaroxaban in the prevention of DVT is reliable, which could significantly reduce the incidence of DVT, alleviate inflammatory reaction and improve blood hypercoagulable state with minor adverse reactions.
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OBJECTIVE: To investigate the regulation effects of main active components in Honghua Injection on cerebrovascular disease network. METHODS: Cerebrovascular disease network was constructed using genes from public database RGD based on the protein-protein interaction (PPI) relationship databases HPRD and BioGRID. Then targets of five main active components in Honghua injection was retrieved from PubMed. Component-target relationships were extracted and associated with PPI in cerebrovascular disease. Component-target network was constructed with Cytoscape 3.1.0. Network analysis technologies were applied to find critical targets, biological pathways and potential synergistic effects among components. RESULTS: The component-target network contains 940 nodes and 2360 edges. MCODE analysis extracted 28 clusters in which 18 clusters had at least 3 nodes. There were 6 clusters with score ≥3, and they were further investigated using BinGO analysis. The results showed that the main biological processes included regulation of macromolecule biosynthetic and metabolic processes, neurogenesis, apoptosis, angiogenesis, immune-inflammation reaction, response to hypoxia stress. Our study also indicated that Hydroxysafflor yellow A and Quercetin may show their cerebrovascular-protective potential based on their synergistic anti-apoptosis effects. CONCLUSION: From the view of molecular network, our study applied network pharmacology methods and technologies to reveal the multi-target, multi-pathway mode of action of Honghua injection on anti-cerebro-vascular disease effects, and the synergistic effects among Hydroxysafflor yellow A and quercetin.
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Objective To conduct a comprehensive evaluation on safety of Honghua Injection through adopting the method of the evidence-based method;To provide reference for clinical reasonable application of Honghua Injection. Methods Computers were used to retrieve some Chinese databases, such as China Biology Medicine, China National Knowledge Infrastructure, Wangfang Database and VIP database. At the same time, other search methods were employed, up to July 2013, including all research types about Honghua Injection. The adverse reactions in the reports of published literature were analyzed by description and statistical analysis. Results Sixty-nine researches on Honghua Injection were included. The total cases of adverse drug reaction (ADR) were 1111, among which male cases were 568 (51%), and female cases were 543 (49%). Thirty-six (52%) papers described ADR of Honghua Injection in detail, and thirty-three (48%) papers just mentioned ADR or did not describe ADR in detail. Skin, skin accessories damage and pathological changes in circulatory system were main contents of ADR. In terms of original diseases, diseases of circulatory system play an important role. Solvent medium was largely in line with its product specification requirements. Most ADR appeared when the drug was used for the first time, from 5 minutes to 5 days. Conclusion The current published literature data show that severe ADR does not happen after the intervention of Honghua Injection.
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Objective The liver is the main target of colon cancer metastasis, and liver metastasis is important and difficult in colon cancer therapy.This study was to investigate the synergistic effects of Honghua injection combined with oxaliplatin in treatment of liver metastasis from colon cancer. Methods Spleen-preserving method was used to establish the model of liver metastasis from colon cancer.The model mice were randomly divided into 5 groups:control group, oxaliplatin group, low dose ( low dose of Honghua injection combined with oxaliplatin) group, medium dose ( medium dose of Honghua injection combined with oxaliplatin) group, high dose (high dose of Honghua injection combined with oxaliplatin) group (n=10).Oxaliplatin were given twice a week at a dose of 5 mg/kg.Honghua injection was given at doses of 2.5, 1.25 and 0.625 g/kg for consecutive 14 days, and the control group received sa-line.After 14 d, all the mice were killed, and the tumor inhibiting rates and liver metastasis rates were calculated.The levels of serum vascular endothelial growth factor ( VEGF) and hepatocyte growth factor ( HGF) were measured by ELISA, and the mRNA expressions of VEGF and HGF in liver were determined by PCR. Results The inhibition rate of low, middle and high dose group achieved 63.2%, 69.2%and 71.4%respectively, which was significantly higher than that of control group (P<0.01).Compared with oxaliplatin group,middle and high dose groups showed a significant higher inhibition rate (P<0.05).Compared with control group, the liver metastasis rates in middle and high dose groups significantly decreased from 90%to 60%and 50%respectively (P<0.05).The serum VEGF and HGF levels showed significant decrease in all treatment groups([83.4 ±25.6],[81.5 ±23.7],[75.8 ±19.4],[72.7 ±20.5] pg/mL),([56.2 ±13.8],[55.4 ±15.7],[48.9 ±13.6],[42.3 ±11.8]pg/mL) compared with control group ([125.3 ±36.2], [98.4 ±26.1]pg/mL) (P<0.01).The mRNA expressions of VEGF and HGF in liver were significantly decreased in all the Hong-hua injection combined with oxaliplatin groups compared with control group ( P<0.05) .Compared with oxaliplatin group, the serum VEGF level in high dose group showed a significant reduced mRNA expression of VEGF (P<0.05). Conclusion Honghua injec-tion can significantly enhance the inhibitory effects of Oxaliplatin on liver metastasis from colon cancer, and the mechanism may con-tribute to the inhibition of VEGF expression and the prevention of angiogenesis in liver.
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Objective To observe the effect of externally-applied Honghua liquid and catus on phlebitis induced by amiodaone.Methods One hundred and two patients with phlebitis induced by injection of amiodaone for the treatment of arrhythmia were randomly divided into control group(n=50)and treatment group(n=52)from January 2012 to December 2013. Patients in the control group were independently treated only by 50 % Honghua liquid, while the patients in the observation group were treated by hot dressing with Honghua liquid followed by wet dressing of catus. The curative effects in both groups were observed and compared.Result The total effective rate in the treatment group was significantly higher than that in the control group(χ2=6.275, P<0.05).Conclusion Hot dressing with Honghua liquid combined with wet dressing with catus is a simple and effective method to treat the phlebitis induced by injection of amiodaone.
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Aim To observe the differences of tonify-ing blood effect for the combination of Danggui and Honghua ( GH) with different proportions on blood de-ficiency mice, and choose the proportion of GH which has the optimal tonifying blood effect. Methods The blood deficient mice model was induced by injection of phenylhydrazine and cyclophosphamide. On the basis of multi-attribute comprehensive index method, the op-timal dose was determined through three doses of GH 1: 1 , which was the highest frequency proportion of GH used in the “Dictionary of Chinese Medicine Prescrip-tions”. According to the optimal dose, the change reg-ulation of tonifying blood effect of GH with different proportions was observed. Results Among three do- ses (1, 3 and 5 times of clinical dose), the tonifying blood effect of GH was best when the dosing concentra-tion of GH was clinical dose. Among nine proportions (1 : 0, 4 : 1, 2 : 1, 3 : 2, 1 : 1, 2 : 3, 1 : 2, 1 : 4 and 0 : 1), GH 1 : 1 had the best effect. Conclusion The results are consistent with regulations of medi-cine usage that GH 1 : 1 has the highest frequency used in Herbal Formulae, which could provide scientif-ic basis for more effective application of Danggui and Honghua in modern clinic medicine.
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[Objective] To investigate the therapeutic effect of Honghua injection plus prednisone and cyclophosphamine on refractory nephrotic syndrom.[Methods] 38 patients with refractory nephrotic syndrom were given intravenous Honghua and cyclophosphamine plus oral prednisone.Serum total cholesterol,triglyceride,liver and renal function,blood routine test,24h protennuria were observed.[Results] Total effective ratio was 92.1%.Cure ratio was 73.68%.Partly cure ratio was 18.42% and ineffective ratio was 7.89%.[Conclusions] Patients with refractory nephrotic syndrom were treated by Honghua injection plus prednisone and cyclophosphamine,which could reduce the application of prednisone,its side effects and enforce its therapeutic effect.What is more,this treatment could lessen therapeutic process,prevent relapse and recoil,protect effectively the retreat syndrom of prednisone as well.
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Objective To investigate the effect of Honghua Injection on the activity of rat liver CYP2D6.Methods The metabolic rates of probe dextromethorphan(DM) in the blank and Honghua Injection groups(0.9,1.8,and 3.6 mL/kg) in vivo urine and in vitro liver microsome incubated system were determined by high performance liquid chromatography(HPLC).The variation of the metabolic rate of DM represented the effect of Honghua Injection on the activity of rat liver CYP2D6 in vivo and in vitro.Results In vivo and in vitro,the DM metabolic rates of treated groups(1.8 and 3.6 mL/kg) are lower than that in the blank group(P
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AIM: To establish a method for determination of volatile components(? pinene、? pinene、camphor、menthol、isoborneol、borneol、cinnamaldehyde、paeonol and laurocapram)in Liangmiao Honghua Ointment (Radix Zanthoxyli, Flos Carthami, Radix Notoginseng, paeonol, etc.). METHODS: Nine volatile components were isolated and determined on ZB WAX capillary column(30 m?0.25 mm?0.25 ?m) by GC. The column temperature was raised by program, 50 ℃(3 min)→30 ℃?min -1 →120 ℃(5 min)→10 ℃?min -1 →150 ℃ (1 min)→60 ℃?min -1 →230 ℃(12 min). Split stream sampling was applied,split ratio was 20∶1; injection port temperature was 210 ℃; detector: FID, temperature at 250 ℃. RESULTS: The nine volatile components were isolated well. The linearities were fine with the recoveries of 97%-100%, respectively. CONCLUSION: The method is convenient,rapid and accurate.It can be used to control the quality of Liangmian Honghua Ointment.
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Objective: To establish a RP HPLC method to determine the content of adenosin in safflower Injection. Methods: The sample was determined by RP HPLC with a Diamonsil TM C 18 column, UV detection wavelength was at 270nm. adenosin used as an external standard and CH 3OH 1% HAC as a mobile phase. Results: The average recovery was 101.86%, RSD was 1.34%. Conclusion: The method is simple and accurate. It can be used to control the quality of Honghua Injection.