Chinese magnoliavine fruit medicinal composition containing radix scutellariae, radix scutellariae, radix salviae miltiorrhizae and radix salviae miltiorrhizae as well as

Abstract

The invention discloses a pharmaceutical composition containing radix astragali, radix salviae miltiorrhizae, radix salviae miltiorrhizae and fructus schizandrae and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine, the pharmaceutical composition containing radix astragali, radix salviae miltiorrhizae, radix salviae miltiorrhizae and fructus schizandrae is prepared from the following raw materials in parts by weight: 30-50 parts of radix astragali, 15-30 parts of radix salviae miltiorrhizae, 15-30 parts of radix codonopsis, 15-30 parts of radix pseudostellariae, 3-5 parts of fructus schizandrae and 10-15 parts of radix et rhizoma rhei. Preferably, the oral medicine dosage forms capable of being prepared comprise hard capsules, tablets and granules. According to the application disclosed by the invention, the expression levels of p38MAPK, JNK and ERK proteins, c-fos mRNA and c-jun mRNA of myocardial tissues of rats in a medicine group are lowest, so that the medicine disclosed by the invention can be used for inhibiting the activity of an MAPK signal channel of the myocardial tissues and inhibiting the expression of related protooncogenes c-fos and c-jun so as to inhibit myocardial fibrosis. Therefore, the medicine can effectively improve the cardiac function of a DCM model rat and relieve myocardial damage, and the effect of the medicine is related to inhibition of MAPK signal channel activity.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicines, and in particular to a Erhuang Sanshen Schisandra chinensis medicinal composition and a preparation method and application thereof. Background Art

[0002] Diabetes is a metabolic syndrome characterized by hyperglycemia due to insufficient insulin secretion and / or insulin action. It is a systemic metabolic disease that can cause multi-system damage and lead to complications such as cardiovascular and cerebrovascular diseases, retinopathy, nephropathy, diabetic foot, and peripheral neuropathy.

[0003] Cardiomyopathy is a group of heterogeneous myocardial diseases, which are caused by different causes of abnormal mechanical and electrical activity of the heart, manifested as inappropriate ventricular hypertrophy or dilatation. Diabetic cardiomyopathy refers to a complication that occurs in patients with diabetes. The disease causes extensive focal necrosis of the myocardium on the basis of metabolic disorders and microvascular lesions.

[0004] At present, Western medicine mainly treats diabetes symptomatically, but cannot cure it radically. Moreover, the effect of Western medicine treatment is single, and the effect of treating diabetic complications is poor. However, traditional Chinese medicine can make up for the shortcomings of Western medicine. According to the basic theory of traditional Chinese medicine, the root cause of diabetes is insufficient spleen transportation and transformation, which leads to the outflow of semen and water and grain essence. However, there is currently a lack of drugs with definite efficacy and high safety for treating diabetic cardiomyopathy. For this reason, a Erhuang Sanshen Schisandrae Chinensis medicinal composition and its preparation method and application are proposed. Summary of the invention

[0005] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, one object of the present invention is to provide a Erhuang Sanshen Schisandrae Chinensis medicinal composition and a preparation method and application thereof.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] The Erhuang Sanshen Schisandra chinensis medicinal composition comprises the following raw materials in parts by weight:

[0008] 30-50 parts by weight of Astragalus, 15-30 parts by weight of Salvia miltiorrhiza, 15-30 parts by weight of Codonopsis pilosula, 15-30 parts by weight of Pseudostellariae pseudoginseng, 3-5 parts by weight of Schisandra chinensis, and 10-15 parts by weight of Rhubarb.

[0009] The preparation method of the Erhuang Sanshen Schisandra chinensis medicinal composition comprises the following steps:

[0010] The medicinal pieces are weighed according to the prescribed dosage, and reflux extracted twice with 5-15 times the amount of 0-60% ethanol, each extraction time is 0.5-1.5 hours, the extracts are combined, the ethanol is recovered, concentrated, dried, crushed, and finally prepared into the required oral drug dosage form.

[0011] Preferably, the oral pharmaceutical dosage forms that can be prepared include hard capsules, tablets, and granules.

[0012] Application of Erhuang Sanshen Schisandrae Chinensis medicinal composition in treating diabetes, cardiomyopathy and diabetic cardiomyopathy.

[0013] Astragalus: It is the dried root of Astragalus membranaceus (Fisch.) Bge.var.mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. of the Leguminosae family.

[0014] Salvia miltiorrhiza: the dried roots and rhizomes of Salvia miltiorrhiza Bge., a plant of the Lamiaceae family.

[0015] Codonopsis: It is the dried root of Codonopsis pilosula (Franch.) Nannf., Codonopsis pilosula Nannf. var. modesta (Nannf.) LTShen or Codonopsis tangshen Oliv. of the Campanulaceae family.

[0016] Pseudostellaria heterophylla: the dried root of Pseudostellaria heterophylla (Miq.) Pax ex Paxet Hoffm. of the Caryophyllaceae family.

[0017] Schisandra chinensis: The dried mature fruit of Schisandra chinensis (Turcz.) Baill., a plant of the Magnoliaceae family.

[0018] Rhubarb: the dried roots and rhizomes of Rheum palmatum L., Rheum tanguticumMaxim.ex Balf. or medicinal rhubarb Rheum officinale Baill. of the Polygonaceae family.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] In the Erhuang Sanshen Schisandra chinensis medicinal composition of the present invention, Codonopsis pilosula and Radix Pseudostellariae strengthen the spleen and replenish qi, promote the production of body fluids and quench thirst, and can promote the absorption of fine substances; Astragalus membranaceus focuses on promoting qi, and with the promotion of qi, it can assist Codonopsis pilosula and Radix Pseudostellariae, and the medicine nourishes spleen yin and absorbs fine substances; Rhubarb clears away heat, and Schisandra chinensis nourishes yin, promotes the production of body fluids and quenches thirst, focuses on clearing heat and nourishing yin, intimidates spleen yin, collects fine substances and prevents them from being lost again, and can assist the digestion of food and water at the same time; Rhubarb treats the symptoms and clears the intestines, and yin deficiency will cause dryness and heat after a long period of illness, and then it will be easy to defecate. Once the bowel movement is smooth, blood sugar will surely drop, and the use of the medicine will be more effective; Rhubarb is a good medicine for moistening the intestines and relieving constipation, and can solve the problems of dry stool accumulation, purging heat and relieving constipation, etc. Salvia miltiorrhiza promotes menstruation and activates blood circulation, clears the heart and relieves vexation, cools blood and eliminates carbuncle, and can relieve the vexation and irritability of diabetic patients and improve microcirculation.

[0021] The Chinese medicines of Astragalus, Codonopsis and Radix Pseudostellariae provided by the present invention have the effects of promoting qi and activating blood circulation, can increase the contractility of the myocardium, reduce the oxygen consumption of the myocardium and improve the cardiac function. Salvia miltiorrhiza can promote blood circulation, clear the heart and relieve vexation, cool blood and eliminate carbuncle, can calm the mind and improve microcirculation. Rhubarb can clear away heat and purge fire, cool blood and detoxify, remove blood stasis and promote menstruation, can improve blood circulation, and Schisandra chinensis and Salvia miltiorrhiza have the effects of nourishing the heart and calming the mind, can stabilize the mind and reduce palpitations.

[0022] The drug of the present invention can significantly improve the cardiac function of diabetic cardiomyopathy model rats, and the levels of cardiac function-related indicators LVEF, AE / A and LVFS are significantly increased, and the levels of myocardial cell injury indicators CK, LDH and myocardial collagen metabolism and myocardial interstitial fibrosis indicator TGF-β1 are reduced, indicating that the drug of the present invention can effectively improve cardiac function, protect myocardial damage, and inhibit myocardial remodeling.

[0023] In the present invention, the expression levels of p38MAPK, JNK, ERK proteins and c-fos mRNA and c-jun mRNA in myocardial tissue of rats in the drug group were the lowest, indicating that the drug of the present invention can inhibit the activity of the MAPK signaling pathway in myocardial tissue, and at the same time inhibit the expression of related proto-oncogenes c-fos and c-jun to inhibit myocardial fibrosis. It can be seen that the drug of the present invention can effectively improve the cardiac function of DCM model rats and reduce myocardial damage, and its effect may be related to the inhibition of the activity of the MAPK signaling pathway. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is a graph showing the expression of p38MAPK, JNK and ERK proteins in myocardial tissue measured by the immunoblotting method in the present invention;

[0025] Figure 2 The following are the pathological changes of myocardial tissues of rats in each group under optical microscope (HE staining, ×200); A: blank control group; B: model group; C: metformin group; D: drug group of the present invention. DETAILED DESCRIPTION

[0026] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0027] Example 1

[0028] The Erhuang Sanshen Schisandra medicinal composition comprises the following components in parts by weight: 30 parts by weight of Astragalus, 15 parts by weight of Salvia miltiorrhiza, 15 parts by weight of Codonopsis pilosula, 15 parts by weight of Pseudostellariae Radix, 5 parts by weight of Schisandrae Chinensis, and 10 parts by weight of Rhubarb.

[0029] The preparation method of the Erhuang Sanshen Schisandra chinensis medicinal composition comprises the following steps: weighing the medicinal pieces according to the prescribed dosage, refluxing and extracting them twice with 10 times and 6 times the amount of 50% ethanol respectively, the first extraction time is 1 hour, and the second extraction time is 0.5 hour, combining the extracts, recovering the ethanol, concentrating, drying, and crushing, and finally preparing the desired oral pharmaceutical dosage form.

[0030] Example 2

[0031] The Erhuang Sanshen Schisandra medicinal composition comprises the following components in parts by weight: 30 parts by weight of Astragalus, 30 parts by weight of Salvia miltiorrhiza, 15 parts by weight of Codonopsis pilosula, 15 parts by weight of Pseudostellariae Radix, 5 parts by weight of Schisandrae Chinensis, and 10 parts by weight of Rhubarb.

[0032] The preparation method of the Erhuang Sanshen Schisandra chinensis medicinal composition comprises the following steps: weighing the medicinal pieces according to the prescribed dosage, refluxing and extracting them twice with 10 times and 6 times the amount of 50% ethanol respectively, the first extraction time is 1 hour, and the second extraction time is 0.5 hour, combining the extracts, recovering the ethanol, concentrating, drying, and crushing, and finally preparing the desired oral pharmaceutical dosage form.

[0033] Example 3

[0034] The Erhuang Sanshen Schisandra medicinal composition comprises the following components in parts by weight: 30 parts by weight of Astragalus, 15 parts by weight of Salvia miltiorrhiza, 30 parts by weight of Codonopsis pilosula, 15 parts by weight of Pseudostellariae Radix, 5 parts by weight of Schisandrae Chinensis, and 10 parts by weight of Rhubarb.

[0035] The preparation method of the Erhuang Sanshen Schisandra chinensis medicinal composition comprises the following steps: weighing the medicinal pieces according to the prescribed dosage, refluxing and extracting them twice with 10 times and 6 times the amount of 50% ethanol respectively, the first extraction time is 1 hour, and the second extraction time is 0.5 hour, combining the extracts, recovering the ethanol, concentrating, drying, and crushing, and finally preparing the desired oral pharmaceutical dosage form.

[0036] Example 4

[0037] The Erhuang Sanshen Schisandra medicinal composition comprises the following components in parts by weight: 30 parts by weight of Astragalus, 15 parts by weight of Salvia miltiorrhiza, 15 parts by weight of Codonopsis pilosula, 30 parts by weight of Pseudostellariae Radix, 5 parts by weight of Schisandrae Chinensis, and 10 parts by weight of Rhubarb.

[0038] The preparation method of the Erhuang Sanshen Schisandra chinensis medicinal composition comprises the following steps: weighing the medicinal pieces according to the prescribed dosage, refluxing and extracting them twice with 50% of 10 times and 6 times the amount respectively, the first extraction time is 1 hour, and the second extraction time is 0.5 hour, combining the extracts, recovering ethanol, concentrating, drying, and crushing, and finally preparing them into the required oral pharmaceutical dosage form.

[0039] Example 5

[0040] The Erhuang Sanshen Schisandra medicinal composition comprises the following components in parts by weight: 30 parts by weight of Astragalus, 30 parts by weight of Salvia miltiorrhiza, 15 parts by weight of Codonopsis pilosula, 15 parts by weight of Pseudostellariae Radix, 3 parts by weight of Schisandrae Chinensis, and 10 parts by weight of Rhubarb.

[0041] The preparation method of the Erhuang Sanshen Schisandra chinensis medicinal composition comprises the following steps: weighing the medicinal pieces according to the prescribed dosage, refluxing and extracting them twice with 50% of 10 times and 6 times the amount respectively, the first extraction time is 1 hour, and the second extraction time is 0.5 hour, combining the extracts, recovering ethanol, concentrating, drying, and crushing, and finally preparing them into the required oral pharmaceutical dosage form.

[0042] Example 6

[0043] The Erhuang Sanshen Schisandra medicinal composition comprises the following components in parts by weight: 30 parts by weight of Astragalus, 30 parts by weight of Salvia miltiorrhiza, 15 parts by weight of Codonopsis pilosula, 15 parts by weight of Pseudostellariae Radix, 3 parts by weight of Schisandrae Chinensis, and 5 parts by weight of Rhubarb.

[0044] The preparation method of the Erhuang Sanshen Schisandra chinensis medicinal composition comprises the following steps: weighing the medicinal pieces according to the prescribed dosage, refluxing and extracting them twice with 50% of 10 times and 6 times the amount respectively, the first extraction time is 1 hour, and the second extraction time is 0.5 hour, combining the extracts, recovering ethanol, concentrating, drying, and crushing, and finally preparing them into the required oral pharmaceutical dosage form.

[0045] Example 7

[0046] The Erhuang Sanshen Schisandra medicinal composition comprises the following components in parts by weight: 50 parts by weight of Astragalus, 30 parts by weight of Salvia miltiorrhiza, 15-30 parts by weight of Codonopsis pilosula, 15-30 parts by weight of Pseudostellariae Pseudostellariae, 3-5 parts by weight of Schisandrae Chinensis, and 10-15 parts by weight of Rhubarb.

[0047] The preparation method of the Erhuang Sanshen Schisandra chinensis medicinal composition comprises the following steps: weighing the medicinal pieces according to the prescribed dosage, refluxing and extracting them twice with 50% of 10 times and 6 times the amount respectively, the first extraction time is 1 hour, and the second extraction time is 0.5 hour, combining the extracts, recovering ethanol, concentrating, drying, and crushing, and finally preparing them into the required oral pharmaceutical dosage form.

[0048] Example 8

[0049] The Erhuang Sanshen Schisandra medicinal composition comprises the following components in parts by weight: 40 parts by weight of Astragalus, 20 parts by weight of Salvia miltiorrhiza, 20 parts by weight of Codonopsis pilosula, 20 parts by weight of Pseudostellariae Radix, 4 parts by weight of Schisandrae Chinensis, and 13 parts by weight of Rhubarb.

[0050] The preparation method of the Erhuang Sanshen Schisandra chinensis medicinal composition comprises the following steps: weighing the medicinal pieces according to the prescribed dosage, refluxing and extracting them twice with 50% of 10 times and 6 times the amount respectively, the first extraction time is 1 hour, and the second extraction time is 0.5 hour, combining the extracts, recovering ethanol, concentrating, drying, and crushing, and finally preparing them into the required oral pharmaceutical dosage form.

[0051] Experimental Example 1

[0052] Experimental purpose: Protective effect of the pharmaceutical composition of the present invention on diabetic cardiomyopathy model rats

[0053] Drugs and reagents:

[0054] (1) Medicines

[0055] The medicine of the present invention: prescription: 30g of Astragalus, 15g of Salvia miltiorrhiza, 15g of Codonopsis pilosula, 15g of Radix Pseudostellariae, 5g of Schisandrae Chinensis, 10g of Rhubarb; preparation method: the medicinal materials are weighed according to the prescribed dosage, and 10 times and 6 times the amount of 50% reflux extraction are respectively used for two times, the first extraction time is 1h, and the second extraction time is 0.5h, the extracts are combined, ethanol is recovered, concentrated, dried, crushed, and finally, prepared into the required oral drug dosage form.

[0056] Streptozotocin (STZ) was purchased from Sigma.

[0057] (2) Reagents

[0058] High-fat diet was purchased from Beijing Botai Hongda Biotechnology Co., Ltd.; rat creatine kinase (CK), lactate dehydrogenase (LDH), and transforming growth factor-β1 (TGF-β1) enzyme-linked immunosorbent assay (ELISA) detection kits were purchased from Jiaozuo Lufeifan Biotechnology Co., Ltd.; p38 mitogen-activated protein kinase (p38MAPK), c-Jun amino-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), β-actin (internal reference) rabbit anti-mouse polyclonal antibodies and horseradish peroxidase (HRP)-labeled goat anti-rabbit IgG were all purchased from Biosino (Tianjin) Biotechnology Co., Ltd.

[0059] Experimental instruments: Prospect small animal ultrasound imaging system, a product of S-Sharp, Japan; FAME fully automatic enzyme-linked immunosorbent assay system, a product of Hamilton, Switzerland; PowerPac Universal electrophoresis instrument, a product of Bio-Rad, USA.

[0060] Experimental animals: Male SD rats, clean grade, weighing (190±10) g, provided by the Experimental Animal Center of Southern Medical University; breeding environment: laboratory of the Experimental Center of Huaqiao Hospital, animals were kept in cages, maintained a 12-h circadian rhythm, room temperature (22±1)℃, and free access to water and food.

[0061] Experimental methods:

[0062] 1. Modeling and grouping

[0063] Ten rats were randomly selected from 42 SD rats as the blank control group, and the others were fed with a high-sugar and high-fat diet (20% sucrose, 10% lard, 3% cholesterol, 1% bile salts and 66% basal diet) for 4 weeks. Then, STZ (dissolved in 0.1% citric acid buffer, pH 4.5, prepared before use) was injected intraperitoneally at 40 mg / kg body weight for 3 consecutive days.

[0064] After 7 days, blood was collected from the tail to measure fasting blood glucose (FBG), and FBG ≧ 16.7 mmol / L was considered a successful diabetic model. The diabetic mice were fed a high-sugar and high-fat diet for 8 weeks, and two rats were randomly selected and killed. The myocardial tissue was stained with HE and Masson to observe changes in myocardial cell morphology. If there were changes such as myocardial disorder, cell hypertrophy, and myocardial fibrosis, it indicated that the rat myocardium was damaged and the diabetic cardiomyopathy model was successfully established.

[0065] Thirty model rats were randomly divided into three groups: model group, metformin group (0.15 / kg), and drug group of the present invention (8.1g / kg). The Chinese medicine group was calculated according to the weight of Chinese medicine beverage. The drug was administered by gavage on the second day after model grouping; the blank control group and model group were gavaged with equal volume of normal saline, once a day, for a total of 4 weeks.

[0066] 2. Sampling and specimen processing

[0067] After the cardiac function test, the rats were weighed, anesthetized, fixed, the chest cavity was opened, the heart was exposed, 3 mL of blood was taken from the left ventricle, and the blood was allowed to stand for 0.5 h. The blood was centrifuged at 3500 r / min for 10 min at 4°C to obtain serum, which was then stored in a -80°C refrigerator. After systemic vascular lavage, the heart was completely peeled off, the surface moisture was blotted, and the heart was weighed; 1 / 2 of the left ventricular myocardial tissue was taken, fixed with 10% neutral formaldehyde, and sliced ​​after dehydration and paraffin embedding, with a thickness of about 4 μm; the remaining 1 / 2 of the left ventricular myocardial tissue was quickly frozen in liquid nitrogen for protein immunoblotting and real-time fluorescence quantitative polymerase chain reaction (PCR) experiments.

[0068] 3. Main testing indicators

[0069] The cardiac function indexes were measured using an ultrasound imaging system. The specific steps were as follows:

[0070] The rats were fasted for 12 hours after the last administration, and the left ventricular ejection fraction (LVEF), peak A to peak E velocity ratio (E / A) and left ventricular fractional shortening (LVFS) of the rats in each group were detected using a small animal ultrasound imaging system.

[0071] Serum CK, LDH and TGF-β1 levels were determined by ELISA. The specific steps were as follows:

[0072] The serum was quickly restored to room temperature, and the serum CK, LDH and TGF-β1 levels were detected using a fully automatic enzyme-linked immunosorbent assay system according to the kit instructions.

[0073] The expression levels of p38MAPK, JNK and ERK proteins in myocardial tissue were determined by immunoblotting. The specific steps are as follows:

[0074] The frozen myocardial tissue was ground, added with cell lysis buffer, fully homogenized and lysed on ice, centrifuged at 14000r / min for 5min, and the supernatant was collected. The total protein content was determined using a diquinoline formic acid protein detection kit to obtain each target protein band. The protein bands were scanned using a gel imaging system and the grayscale value of each protein band was analyzed to calculate the expression of p38MAPK, JNK, and ERK proteins relative to the internal reference β-actin.

[0075] The expression levels of c-fos mRNA and c-jun genes in myocardial tissue were determined by real-time fluorescence quantitative PCR. The specific steps were as follows:

[0076] The frozen myocardial tissue was fully ground, and the total RNA was extracted according to the steps in the total RNA extraction kit manual, and the total RNA content was calculated; primers for c-fos mRNA, c-jun mRNA, and internal reference glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were designed and reverse transcribed into corresponding cDNA using a reverse transcription kit; 2 μL of cDNA was taken and the real-time PCR reaction system was prepared according to the manual, and the reaction conditions were set as 95°C pre-denaturation for 3 min, 95°C denaturation for 5 s per cycle, 60°C annealing and extension for 30 s, and a total of 40 cycles.

[0077] The ΔCt values ​​of c-fos mRNA and c-jun mRNA were determined by real-time fluorescence quantitative PCR system. The quantitative results were calculated by 2-ΔΔCt method to obtain the relative expression levels of c-fos mRNA and c-jun mRNA.

[0078] The pathological changes of myocardial tissue sections were observed using the hematoxylin-eosin (HE) staining method. The specific steps are as follows:

[0079] The prepared tissue sections were routinely dewaxed with xylene, ethanol gradient concentrations to water, and stained with hematoxylin solution for 5 minutes according to the literature method. The pathological changes of myocardial tissues of rats in each group were observed under an optical microscope.

[0080] SPSS 22.0 software package was used to analyze the normal measurement data. One-way ANOVA was used for comparison among multiple groups, and LSD-t test was used for multiple comparison among groups.

[0081] Experimental results:

[0082] Compared with the model group, the levels of LVEF, E / A and LVFS in the drug-treated group were significantly improved, and the differences were statistically significant (all P < 0.05). See Table 1.

[0083] Group LVEF (%) E / A LVFS(%) Blank control group 77.54±8.74 1.32±0.09 34.3±4.2 Model Group 47.44±5.95* 0.73±0.05* 24.5±4.4* Metformin group 65.75±4.7# 1.10±0.06# 32.3±3.4# The drug combination of the present invention 67.26±3.89# 1.15±0.05# 33.54±4.12#

[0084] Table 1 Comparison of left ventricular ejection fraction (LVEF), peak A to peak E velocity ratio (E / A) and left ventricular fractional shortening (LVFS) in rats of each group There were 10 mice in each group; compared with the blank control group, *P<0.05; compared with the model group, #P<0.05

[0085] Compared with the model group, the levels of CK, LDH and TGF-β1 in the drug-treated group were significantly decreased, and the differences were statistically significant (all P < 0.05), as shown in Table 2.

[0086] Group CK(U / L) LDH (U / L) <![CDATA[TCF-β 1 (pg / ml)]]> Blank control group 325.89±20.40 391.99±25.80 411.79±25.60 Model Group 530.39±25.82* 601.77±26.07* 635.61±21.81* Metformin group 368.12±30.80# 425.34±26.21* 443.73±23.69* The drug combination of the present invention 378.62±36.28# 435.96±29.38* 461.28±22.86*

[0087] Table 2 Serum creatine kinase (CK), lactate dehydrogenase (LDH) and transforming growth factor β in rats in each group 1 (TGF-β 1 ) Level comparison

[0088]

[0089] There were 10 mice in each group; compared with the blank control group, *P<0.05; compared with the model group, #P<0.05

[0090] Comparison of p38MAPK, JNK, and ERK protein expression levels in myocardial tissue of rats in each group Compared with the model group, the p38MAPK, JNK, and ERK protein expression levels in the drug-treated group were significantly reduced, and the differences were statistically significant (all P < 0.05), as shown in Table 3 and Appendix Figure 1 .

[0091] Group P38MAPK JNK ERK Blank control group 0.51±0.07 1.58±0.12 0.66±0.11 Model Group 1.15±0.11* 2.72±0.22* 2.10±0.25* Metformin group 0.61±0.06# 1.88±0.10# 0.83±0.14# The drug combination of the present invention 0.64±0.06# 1.92±0.11# 0.86±0.15#

[0092] Table 3 Comparison of protein expression levels of p38 mitogen-activated protein kinase (p38MAPK), c-Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in myocardial tissue of rats in each group

[0093] There were 10 mice in each group; compared with the blank control group, *P<0.05; compared with the model group, #P<0.05

[0094] Compared with the model group, the expression levels of c-fos mRNA and c-jun mRNA in the drug-treated group were significantly reduced, and the differences were statistically significant (all P < 0.05), as shown in Table 4.

[0095] Group c-fosmRNA c-jun mRNA Blank control group 1.48±0.12 2.58±0.10 Model Group 11.63±0.38* 8.63±0.6* Metformin group 1.92±0.12# 3.21±0.36# The drug combination of the present invention 2.04±0.11# 3.32±0.25#

[0096] Table 4 Comparison of c-fos mRNA and c-jun mRNA expression levels in myocardial tissue of rats in each group

[0097] 10 mice in each group; compared with the blank control group, *P<0.05; compared with the model group, #P<0.05

[0098] The myocardial structure of the blank control group was normal, the myocardial cells were evenly stained and arranged neatly, there was no cell swelling, and no collagen fibers; the myocardial cells of the rats in the model group were unevenly stained, abnormal in morphology, condensed or lysed nuclei, and a large number of myocardial cells showed varying degrees of swelling, fatty degeneration, disordered arrangement, and severe inflammatory cell infiltration and collagen fiber hyperplasia in the intercellular matrix; the myocardial cell structure of the rats in the drug group was basically clear, a small number of cells were swollen, fatty degeneration, and arranged more regularly, and there was very little inflammatory cell infiltration and collagen fiber hyperplasia in the intercellular matrix, see attached Figure 2 .

[0099] Experimental conclusion:

[0100] The results of the study showed that the drug of the present invention can significantly improve the cardiac function of rats with diabetic cardiomyopathy model, and the levels of cardiac function-related indicators LVEF, AE / A and LVFS are significantly increased, while the levels of myocardial cell injury indicators CK, LDH and myocardial collagen metabolism and myocardial interstitial fibrosis indicator TGF-β1 are reduced, indicating that the drug of the present invention can effectively improve cardiac function, protect myocardial damage and inhibit myocardial remodeling.

[0101] The expression levels of p38MAPK, JNK, ERK proteins, c-fos mRNA, and c-jun mRNA in myocardial tissue of rats in the drug group of the present invention were the lowest, indicating that the drug of the present invention can inhibit the activity of the MAPK signaling pathway in myocardial tissue, and at the same time inhibit the expression of related proto-oncogenes c-fos and c-jun to inhibit myocardial fibrosis. It can be seen that the drug of the present invention can effectively improve the cardiac function of DCM model rats and reduce myocardial damage, and its effect may be related to the inhibition of the activity of the MAPK signaling pathway.

[0102] In summary, the present invention provides a pharmaceutical composition and a preparation method thereof according to the basic theories of traditional Chinese medicine and the experience of previous prescriptions. The drug has a definite therapeutic effect in preventing and treating T2DM and improving myocardial function. The drug of the present invention can not only improve the symptoms of diabetes, but also improve insulin resistance, and has a certain effect of improving myocardial function.

[0103] Parts not involved in the present invention are the same as the prior art or can be implemented by the prior art. Although the embodiments of the present invention have been shown and described, it is understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. Erhuang Sanshen Schisandra chinensis medicinal composition, characterized in that, The invention comprises the following raw materials in parts by weight: 30-50 parts by weight of Astragalus, 15-30 parts by weight of Salvia miltiorrhiza, 15-30 parts by weight of Codonopsis pilosula, 15-30 parts by weight of Pseudostellariae pseudoginseng, 3-5 parts by weight of Schisandra chinensis, and 10-15 parts by weight of Rhubarb.

2. A method for preparing a Erhuang Sanshen Schisandrae Chinensis medicinal composition, characterized in that: The following steps are involved: The medicinal pieces are weighed according to the prescribed dosage, and reflux extracted twice with 5-15 times the amount of 0-60% ethanol, each extraction time is 0.5-1.5 hours, the extracts are combined, the ethanol is recovered, concentrated, dried, crushed, and finally prepared into the required oral drug dosage form.

3. The method for preparing the Erhuang Sanshen Schisandrae Chinensis medicinal composition according to claim 2, characterized in that: The oral drug dosage forms that can be prepared include hard capsules, tablets, and granules.

4. Application of Erhuang Sanshen Schisandrae Chinensis medicinal composition in the treatment of diabetes, cardiomyopathy, and diabetic cardiomyopathy.

Images