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The purpose of the current study was to evaluate the optimal compatibility proportion of 18α-Glycyrrhizic acid (18α-GA) and 18ß-Glycyrrhizic acid (18ß-GA) against carbon tetrachloride (CCl4)-induced hepatic damage in rats, and further explored the underlying mechanism. Rats were injected with CCl4 (0.1%, 0.3â¯ml/kg) once a week and were orally administrated with different proportions of 18α-, and 18ß-GA daily for 4 weeks. Rats were then sacriï¬ced and blood samples were collected for biochemical assay. Liver tissues were assessed histologically for severity of liver injury. Enzyme activities in liver homogenate were determined using commercial kits. The mRNA levels of associated proteins were evaluated by RT-PCR. The data showed that the combination of 18α-, and 18ß-GA, especially at proportion of 4:6, obviously alleviated CCl4-induced liver injury as evidenced by the improvement of liver histopathological changes, and decreased levels of ALT and AST in serum. Moreover, 18α- and 18ß-GA at all proportions substantially improved glucose tolerance, and markedly reversed the decrease of SOD, MDA, and GSH, and increase of lipid markers (TG, TC, HDL, LDL) induced by CCl4 via regulating the mRNA levels of SREBP-1c, ACC, PPAR-α, and CPT-1a. Collectively, these results suggested that 18α-GA in combination with 18ß-GA, especially at proportion of 4:6, effectively reduced liver injury induced by CCl4, comparable to the positive control silibinin, and the mechanism may be associated with reduced marker of liver oxidative stress and improvement of lipid metabolism via regulation of ACC, CTP-1A, PPARα, and SREBP1.
Assuntos
Tetracloreto de Carbono/farmacologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Ácido Glicirrízico/farmacologia , Fígado/efeitos dos fármacos , Acetil-CoA Carboxilase/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Intoxicação por Tetracloreto de Carbono , Glucose/metabolismo , Teste de Tolerância a Glucose , Glutationa/metabolismo , Lipídeos/sangue , Fígado/patologia , Malondialdeído/metabolismo , Ratos Sprague-Dawley , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Objective: To screen the best compatibility proportion of total alkaloids of Coptidis Rhizoma and Notoginseng Radix et Rhizoma total saponins (HS composition)by uniform design and pharmacological model and to observe the effect on diabetic complications. Method: The total alkaloids of Coptidis Rhizoma and Notoginseng Radix et Rhizoma total saponins were used as the research objects, U6(62) table was choosed for grouping design.The content of triglyceride fasting blood-glucose (FBG), prothrombin time (PT) and active partial thromboplastin time (APTT) was chosen as index. The best dose ratio was obtained by multipleregression analysis. Rats with type 2 diabetes mellitus induced by high-fat diet combined streptozotocin were divided into blank group, model group, metformin group (150 mg·kg-1), HS composition group (total alkaloids of Coptidis Rhizoma 360 mg·kg-1+ Notoginseng Radix et Rhizoma total saponins 40 mg·kg-1). Rats were administered orally for 10 weeks.By observing the blood glucose, glucose tolerance,area under the curve (AUC), triglyceride (TG), high-density lipoprotein (HDL-C)and low-density lipoprotein (LDL-C), hemorheological indexes and pathological changes of pancreas, heart, kidney and retina in rats of each group, the effect of this composition on diabetic complications was verified. Result: Combination of 625 mg·kg-1 total alkaloids of Coptidis Rhizoma and 60 mg·kg-1 Notoginseng Radix et Rhizoma total saponins was the optimal dosage ratio of HS composition.The validation test showed that compared with blank group, the fasting blood glucose and lipid levels in the model group were significantly increased (PPPPPPPPPPPConclusion: The optimum compatibility dose of HS composition have a good therapeutic effect on diabetic complication rats induced by high-fat diet and streptozotocin.
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Objective:To optimize proportion of couplet medicine of Bupleuri Radix and Scutellariae Radix in the treatment of anti-depression, and to explore the possible antidepressant mechanism of this couplet medicine. Method:The dosages of Bupleuri Radix and Scutellariae Radix in the 2015 edition of Chinese Pharmacopoeia were taken.According to U7(72) uniform design table, Bupleuri Radix and Scutellariae Radix were carried out into 7 groups.The chronic unpredictable mild depression model mice were induced by intragastric administration of decoction of this couplet medicine and the antidepressant effect was observed by the behavior tests, which included sucrose preference test, tail suspension test, forced swimming test and open field test(crossing scores).The regression equations were established by selecting the effective indexes.The experiments of retest were taken to check the results and the possible antidepressant mechanism was primarily investigated by measuring the phosphorylation level of cyclic adenosine monophosphate(cAMP)-response element binding protein(CREB) and expression of brain-derived neurotrophic factor(BDNF). Result:Compared with the blank group, sucrose preference rate of the model group was significantly decreased(PPPPPPPPPPPPPPConclusion:Compatibility of Bupleuri Radix and Scutellariae Radix can ameliorate depressive-like behavior of model mice, and the best antidepressant compatibility proportion of Bupleuri Radix and Scutellariae Radix is 1:1, the optimal amounts of them are about 5 g.The antidepressant effect may relate to promoting phosphorylation level of CREB and the expression of BDNF in the hippocampus.
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OBJECTIVE: To investigate the best compatibility proportion of Mongolian medicine “Terminalia chebula decomposing the poison of Aconitum kusnezoffii”. METHODS: Totally 40 rats were randomly divided into blank control group (0.05% CMC-Na), raw A. kusnezoffii group (0.12 g/kg by crude drug) and raw A. kusnezoffii-T. chebula (1 ∶ 3,1 ∶ 1,3 ∶ 1, mass ratio) group (0.12 g/kg raw A. kusnezoffii by raw material), 8 rats in each group. They were given relevant medicine intragastrically once a day, for consecutive 28 d. 0.5 h after last medication, serum contents of cTn-I and MB were determined, and the changes of cardiological structure were observed; the detoxification effects of T. chebula on cardiotoxicity induced by A. kusnezoffii were investigated. Binding rates of 3 kinds of aconitine (concentrations of aconitine, mesaconitine and hypaconitine were 5, 10, 20, 40, 80, 160, 400 ng/mL) to binding rate of plasma protein with normal human plasma were determined by equilibrium dialysis combined with liquid chromtography-mass spectrometry. The concentrations of 3 kinds of aconitine were fixed as 100 ng/mL. After adding main detoxification component tannic acid in different proportions of T. chebula (1 ∶ 0.025, 1 ∶ 0.075, 1 ∶ 0.1, 1 ∶ 0.5), the effects of them on plasma protein binding rate of 3 kinds of aconitine were investigated; the possible mechanism of T. chebula decomposing the poison of A. kusnezoffii inducing cardiotoxicity were investigated. RESULTS: In detoxification experiment, compared with blank control group, serum contents of cTn-I and MB were increased significantly in raw A. kusnezoffii group (P<0.05). There were obvious pathological changes in myocardial tissue, such as disorder of cell arrangement, cell shrinkage and cytoplasm staining. Compared with raw A. kusnezoffii group, serum contents of cTn-I and MB in raw A. kusnezoffii-T. chebula (1 ∶ 3, 1 ∶ 1, 3 ∶ 1) groups were decreased significantly (P<0.05), and there was no significant difference between the raw A. kusnezoffii-T. chebula (3 ∶ 1, 1 ∶ 1) groups and blank control group (P>0.05); myocardial pathological changes were improved to varying degrees. The structure of myocardial tissue in raw A. kusnezoffii-T. chebula (3 ∶ 1) groups were similar to blank control group. In the mechanism investigation experiment under the condition of different concentrations, plasma protein binding rates of 3 kinds of aconitine with normal human plasma were about 30%, without statistical significance (P>0.05) and significant concentration-dependent manner. After adding tannic acid, plasma protein binding rate of 3 kinds of aconitine in A. kusnezoffii was decreased to different extent; when 3 kinds of aconitine were combined with tannic acid in the ratio of 1 ∶ 0.1, 1 ∶ 0.075 and 1 ∶ 0.5, the plasma protein binding rate decreased significantly (P<0.05), in proportion-dependent manner. CONCLUSIONS: Compatible use of raw A. kusnezoffii-T. chebula (3 ∶ 1) show that best detoxification effect on A. kusnezoffii-induced cardiotoxicity. Under this compatibility ratio, the plasma protein binding rate of 3 kinds of aconitine in A. kusnezoffii with normal human plasma is relatively high and the free drug concentration is relatively low.
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OBJECTIVE: To study the effects and mechanism of couplet medicines of Scutellaria baicalensis-Paeonia lactiflora on improving ulcerative colitis (UC) in mice. METHODS: A total of 70 mice were randomly divided into blank group, model group, S. baicalensis group (1. 5 g/kg), P. lactiflora group (1. 5 g/kg), S. baicalensis-P. lactiflora (2:1, 1:1, 1:2, m/m) groups (total amount of 1. 5 g/kg), with 10 mice in each group. Except for blank group, UC model of mice was induced in each group. The next day after modeling, treatment groups were given relevant medicine liquid 0. 2 mL/10 g (75 mg/mL, calculated by crude drug mass concentration), while blank group and model group were given constant volume of normal saline intragastrically, once a day, for consecutive 7 d. After administration, disease activity indexes (DAI) of rats were scored, and the serum levels of TNF-α, IL-1β, IL-6, D-LA and myeloperoxidase (DAO) were determined. The length of the colon was measured and the intestinal mass index was calculated in mice. The activities of medullary peroxide (MPO) and SOD, the levels of NO and MDA were determined in colon tissue. RESULTS: Compared with blank group, DAI score, serum levels of TNF-α, IL-1β, IL-6, D-LA and DAO, the levels of MPO, NO and MDA in colon were increased significantly in model group, while the length of colon, intestinal mass index and SOD level of colon tissue were decreased significantly, with statistical significance (P<0. 05 or P<0. 01). Compared with model group, DAI score, serum levels of TNF-α, IL-1β and DAO, the level of MDA in colon were decreased significantly in S. baicalensis group (P<0. 05 or P<0. 01). The serum levels of TNF-α and IL-1β, the level of MDA in colon were decreased significantly in P. lactiflora group (P<0. 05 or P<0. 01). Above indexes of S. baicalensis-P. lactiflora (2:1) group were improved significantly except for the length of colon (P<0. 05 or P<0. 01). Above indexes of S. baicalensis-P. lactiflora (1:1) group were improved significantly except for serum level of IL-6 and the level of SOD in colon (P<0. 05 or P<0. 01). Above indexes of S. baicalensis-P. lactiflora (1:2) group were improved significantly except for serum level of NO (P<0. 05 or P<0. 01). CONCLUSIONS: The couplet medicines of S. baicalensis-P. lactiflora can reduce the expression of proinflammatory factors, enhancing antioxidant activity of the body and decrease intestinal mucosal permeability so as to improve UC symptom of mice; and the effect of S. baicalensis-P. lactiflora (2:1) group is the best.
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Objective To study the similarity of chemical fingerprints of different proportion of Gualoupi-Gualouzi and Fruc?tus Trichosanthis,so as to provide the theoretical basis for the reasonable proportion of Gualoupi-Gualouzi. Methods The HPLC fin?gerprints and the common patterns of 6 the proportion of the 6 kinds of compatibility(30:70,35:65,40:60,45:55,50:50 and 55:45)of Gualoupi-Gualouzi and Fructus Trichosanthis were established,and the similarity of chemical fingerprints of different compati?bility proportion of Gualoupi-Gualouzi and Fructus Trichosanthis between their common patterns were compared. Results Compared with the common pattern of Fructus Trichosanthis,the similarities of the common patterns of chemical fingerprints of the above 6 kinds of compatibility proportion of Gualoupi-Gualouzi were 0.8808 ± 0.0407,0.8930 ± 0.0236,0.8995 ± 0.0195,0.9033 ± 0.0190,0.9363 ± 0.0082 and 0.8904 ± 0.0144,respectively. Among them,Gualoupi-Gualouzi ratio of 50:50 had the highest similarity,and compared with other groups,the differences were statistically significant(P<0.05 or 0.01). Conclusion The optimum proportion of Gualoupi-Gualouzi can be determined by the fingerprint technology,which provides the theoretical basis for the reasonable proportion of Gualou?pi-Gualouzi.
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Objective To study the similarity of chemical fingerprints of different proportion of Gualoupi-Gualouzi and Fructus Trichosanthis, so as to provide the theoretical basis for the reasonable proportion of Gualoupi-Gualouzi. Methods The HPLC fingerprints and the common patterns of 6 the proportion of the 6 kinds of compatibility (30∶70, 35∶65, 40∶60, 45∶55, 50∶50 and 55∶ 45) of Gualoupi-Gualouzi and Fructus Trichosanthis were established, and the similarity of chemical fingerprints of different compatibility proportion of Gualoupi-Gualouzi and Fructus Trichosanthis between their common patterns were compared. Results Compared with the common pattern of Fructus Trichosanthis, the similarities of the common patterns of chemical fingerprints of the above 6 kinds of compatibility proportion of Gualoupi-Gualouzi were 0.8808±0.0407, 0.8930±0.0236, 0.8995±0.0195, 0.9033±0.0190, 0.9363± 0.0082 and 0.8904±0.0144, respectively. Among them, Gualoupi-Gualouzi ratio of 50∶50 had the highest similarity, and compared with other groups, the differences were statistically significant (P<0.05 or 0.01). Conclusion The optimum proportion of Gualoupi- Gualouzi can be determined by the fingerprint technology, which provides the theoretical basis for the reasonable proportion of Gualou⁃pi-Gualouzi.
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Objective To observe the best compatibility proportion and action mode of protective effects of combined baicalin and taurine in Alzheimer’s disease (AD) model.Methods Aβ1-42 was injected through lateral ventricles to establish AD rat models. SD rats were randomly divided into sham-operation group, model group, aricept group, combined baicalin and taurine in different proportions group. Administration groups were treated with different medicines, while sham-operation group and model group were treated with the same amount of normal saline for 40 days. The step-through latency and the times of mistakes were detected through step-through test;the escape latent and the times of crossing target quadrant were detected through Morris water maze. Furthermore, the human neuroblastoma SH-SY5Y cells were induced by 5 μmol/L Aβ1-42 for establishing a cellular AD model. The AD cellular model was treated with baicalin and taurine compatibility in different proportions for 48 hours. Then the rate of cell viability was detected by MTT assay, and the median effective concentration (EC50) and combination index were calculated. Results Baicalin and taurine in 2∶1 and 1∶1 proportion groups can significantly improve learning and memory ability in AD rats (P<0.05,P<0.01). The EC50 were 2.110 μmol/L and 0.422 μmol/L, respectively. The combination index was 0.308.Conclusion Baicalin combined with taurine exhibit synergetic protective effects in AD rats induced by Aβ1-42. The optimal compatibility proportion of baicalin and taurine is 2∶1, and EC50 is 0.279 μmol/L.
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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.