CN113350394A - Application of compound geranium wilfordii in preparation of medicine for treating diabetic nephropathy - Google Patents
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Abstract
The invention relates to an application of compound geranium wilfordii in preparing a medicine for treating diabetic nephropathy, the main component of the compound geranium wilfordii is a flavonoid compound, and research results show that the compound geranium wilfordii has the effects of obviously reducing the expression amount of albumin in urine and reducing the urinary creatinine content after long-term administration to db/db mice with type 2 diabetes, so that the damage of the kidney is improved, support is provided for the research and development of new medicines of the compound geranium wilfordii, and basis is provided for explaining the scientificity of the application of the traditional Chinese medicine in the treatment of the diabetic nephropathy.
Description
Technical Field
The invention relates to application of compound geranium wilfordii in preparing a medicine for treating diabetic nephropathy.
Background
Diabetes mellitus is a metabolic disorder syndrome characterized by hyperglycemia due to defective insulin secretion and/or insufficient insulin action. According to the international diabetes union (IDF) statistics, 4.25 hundred million people suffer from diabetes in 2017 globally, and the number of diabetes patients in the world is estimated to increase to 6.29 hundred million by 2045. The mortality rate of diabetes is greater than the sum of the mortality rates of AIDS, tuberculosis and malaria. Diabetic nephropathy is one of the most serious microvascular complications of diabetes, is also the leading cause of end-stage renal disease, and imposes a heavy economic burden on the families and society of patients, so that prevention and treatment are very important. However, the pathogenesis of the disease is still unclear at present, and various factors such as hemodynamic pathways, hyperglycemia, inflammatory factors, genetic predisposition, hypertension, lipid metabolism disorder, environmental factors and the like can be involved. A large number of researches prove that hyperglycemia is the most main risk factor of diabetic nephropathy, and poor blood sugar control is closely related to occurrence and development of the diabetic nephropathy. Abnormal glucose metabolism can cause increased glomerular filtration rate, resulting in hypertrophy and hyperplasia of the glomeruli. In addition, persistent hyperglycemia promotes the formation of advanced glycation end products of glucose, lipids, proteins and DNA molecules, which are deposited in the kidney, further burdening the kidney. Therefore, the blood sugar is effectively controlled within the normal range, and the damage of the hyperglycemic state to the kidney can be obviously reduced. Urine protein, inflammatory response and blood creatinine are common markers for clinical diagnosis and prediction of diabetic nephropathy, but have no obvious advantages in sensitivity and specificity. Clinical studies have shown that increased proteinuria is an important manifestation of glomerular injury and also a hallmark of progressive renal damage in diabetic nephropathy patients. Diabetic nephropathy is characterized by increased permeability of the glomeruli to proteins and accumulation of mesangial extracellular matrix components, resulting in proteinuria and progressive decline in renal function. The inflammatory response may contribute to the development of diabetic nephropathy. Research shows that inhibiting inflammatory reaction can prevent the development of diabetic nephropathy and improve renal function of patient. The traditional Chinese medicine compound preparation has irreplaceable effect on treating complex chronic diseases, and residents and patients in Asian regions have higher acceptance for local medicinal plant resources due to living habits of medicine and food homology.
The compound geranium wilfordii is composed of geranium wilfordii on hills and hypericum delavayi, the medical application of the compound geranium wilfordii is recorded in Chinese pharmacopoeia, Uyghur medical records and Alweisenna medical records, the compound geranium wilfordii is a classic proved prescription with obvious clinical curative effect, and the extracts of the two medicinal materials according to a specific ratio have hypoglycemic activity. Chinese patent 2016100560799A compound herba Erodii seu Geranii for treating diabetes, and its preparation method are provided. In addition, the previous research results also confirm that the compound has no toxic effect on high glucose insulin resistance model L6 skeletal muscle cells in the concentration range of 3.125-200. mu.g/mL, and the glucose consumption of L6 cells can be effectively promoted by observing the concentration of 6.25. mu.g/mL, wherein the action mechanism of the compound is that the compound relieves endoplasmic reticulum stress reaction by inhibiting the expression of GRP78 protein and activating PERK/eIF2 alpha signal channel, thereby playing a role in improving insulin resistance (Salame Eders, Lan Jiang, XueLei Xin, Haji Akber Aisa, anti-diabetes effect and mechani of Kursi Wufarikun Ziyabit in L6 rate skin cells. journal of Pharmacological Sciences 137(2018), Pharmacological Sciences 212 and 219). The compound herba Erodii seu Geranii has great medical value.
Because of the difference of the treatment mechanism and the treatment principle of diabetes and diabetic nephropathy, no medicine can treat the diabetes and the diabetic nephropathy simultaneously in the prior art, and a good treatment effect can be achieved. The invention provides the application of compound geranium wilfordii in preparing a medicine for treating diabetic nephropathy by further researching the compound geranium wilfordii on the basis of Chinese patent 2016100560799, namely a compound geranium wilfordii herbal medicine for treating diabetes and a preparation method thereof.
Disclosure of Invention
The invention aims to provide application of compound geranium wilfordii in preparing a medicine for treating diabetic nephropathy, which is a new application further researched on the basis of Chinese patent 2016100560799, namely a compound geranium wilfordii medicine for treating diabetes and a preparation method thereof, wherein the main component of the compound geranium wilfordii is a flavonoid compound, and research results show that the compound geranium wilfordii has the effects of obviously reducing the expression amount of albumin in urine and reducing the urinary creatinine content after long-term administration to a db/db mouse with type 2 diabetes, so that damage to the kidney is improved, a support is provided for research and development of new medicines of the compound geranium wilfordii, and a basis is provided for explaining the scientificity of application of the traditional Chinese medicine in treating diabetic nephropathy.
The invention relates to application of compound geranium wilfordii in preparing a medicine for treating diabetic nephropathy.
According to the application of the compound geranium wilfordii in preparing the medicine for treating diabetic nephropathy, a series of animal experiments prove that the compound geranium wilfordii has the effect of reducing blood sugar activity and can be used for treating diabetic nephropathy, the expression level of albumin can be reduced, the content of creatinine is reduced, and therefore kidney damage is improved, and the compound geranium wilfordii has an application prospect in being developed into the medicine for treating diabetic nephropathy.
The invention relates to an application of compound geranium wilfordii in preparing a medicine for treating diabetic nephropathy, wherein the compound geranium wilfordii related in the application is a compound geranium wilfordii herbal medicine for treating diabetes and a preparation method thereof in Chinese patent 2016100560799, the compound geranium wilfordii medicine for treating diabetes comprises 50-90 parts by weight of geranium wilfordii root and 10-60 parts by weight of hypericum delavayi overground part, and the auxiliary material is starch, dextrin, mannitol or sodium carboxymethyl starch 10-50 parts by weight, and the extract is obtained by extraction, purification and drying, and then the extract and the auxiliary material are prepared into particles, capsules or tablets by a conventional method.
The preparation method of the compound geranium wilfordii medicine for treating diabetes comprises the following steps:
a. pulverizing 50-90 parts by weight of dried geranium wilfordii root and 10-60 parts by weight of overground part of hypericum crassimum, extracting for 1-3 times by refluxing with 5-30 times of ethanol with volume concentration of 30% -80% at 30-90 ℃ for 1-3 hours each time, combining the extracting solutions, filtering, and concentrating the filtrate under reduced pressure until no alcohol smell exists to obtain an extracting solution;
b. filtering the extracting solution obtained in the step a, purifying the filtrate by using resin columns such as HP-600, AB-8, D101, HPD-300, LD601, DM-130 or LX-38, eluting by using water with the volume of 1-4 times of the column volume, eluting by using 30-90% ethanol with the volume of 3-8 times of the column volume, collecting ethanol eluent, concentrating under reduced pressure, drying and crushing to obtain an extract;
c. and (c) uniformly mixing the extract obtained in the step (b) with 10-50 parts of medical grade auxiliary materials, namely starch, dextrin, mannitol or sodium carboxymethyl starch, and preparing into granules, capsules or tablets by a conventional pharmaceutical method.
Drawings
FIG. 1 is a SDS-PAGE analysis result chart of urine albumin of db/db mice of each dose group of the compound Geranium wilfordii of the invention, wherein A: a diabetes model group (Vehicle) and a positive drug Metformin group (Metformin) db/db mouse urine albumin SDS-PAGE analysis result chart; b: SDS-PAGE analysis result chart of urine albumin of db/db mice of 2 dose groups of compound geranium wilfordii (compound geranium wilfordii-80 and compound geranium wilfordii-160).
Fig. 2 is a graph of the results of urine glucose and urine creatinine content determination and analysis of db/db mice in each dose group of the compound geranium wilfordii of the present invention, wherein a: the urine sugar content; and B: urinary creatinine content; each group consisted of 8 mice.
Detailed Description
The invention discloses application of compound geranium wilfordii in preparing a medicine for treating diabetic nephropathy, and experimental results are analyzed by GraphPad Prism software. Data are expressed as Mean ± standard error (Mean ± SEM) and evaluated by t-test, dose group compared to model group, to*P<0.05，**P<0.01，***P<And 0.001.
The materials, reagents and the like used are commercially available unless otherwise specified.
The mice in this example were all healthy male/female BKS. Cg-Dock7m +/+ Leprdb/J mice (db/db mice), aged 6-7 weeks, weighing 30-40 g.
In the embodiment, the compound geranium wilfordii is brown solid powder, and is prepared by using distilled water, normal saline or other pharmaceutically acceptable carriers as solvents.
Example 1
The influence of the compound geranium wilfordii on the expression condition of albumin in urine of diabetic db/db mouse:
selecting 32 db/db mice (independently bred after being introduced from Jackson laboratories of Shanghai pharmaceutical research institute of China academy of sciences) with random blood sugar of more than 11.1mmoL/L meeting the requirements of animal models of diseases, dividing the mice into 4 groups according to the random blood sugar, random weight, fasting blood sugar and fasting weight of the mice, wherein each group comprises 8 mice and 5 males and 3 females; respectively setting as model control group, 2 doses of compound herba Erodii seu Geranii, and positive control metformin group, and setting a group of db/db mice normal mice in the same nest as normal control; the specific grouping is as follows:
TABLE 1 herbal effect test design and dosage of compound Geranium wilfordii
Experiments are carried out on each group of experimental subjects according to the experimental design method in the table 1, all the medicines are used in the on-site preparation, are taken once a day and are orally taken for intragastric administration, and the dosage is p.o., 0.1mL/10 g; mouse body weight was measured weekly (fixed time); intake measurements (calculated as the difference between added and remaining water and feed); blood glucose measurements once a week (fixed time); collecting and recording urine of each group of mice for 24 hours after administration for 4 weeks, and then measuring the urine albumin expression of each group of mice;
as can be seen from fig. 1, the electrophoresis strip results of the urine of each group of mice show that, compared with the model group (fig. 1A), the albumin expression level at 70KDa of each dose group of mice of compound geranium wilfordii (fig. 1B) is reduced, and the tubular protein and glomerular protein expression level is lower, which indicates that each dose of compound geranium wilfordii obviously reduces the damage of the kidney of the diabetic mice.
Example 2
The influence of the blood sugar-reducing effective part of the compound geranium wilfordii on the creatinine content in urine of a diabetic db/db mouse is as follows:
in order to further determine the influence of the compound geranium wilfordii on the kidney and liver functions of each group of diabetic db/db mice, the sugar content and the creatinine content in the urine of each group of diabetic mice in 24 hours are determined according to the results of example 1, and the results are shown in fig. 2;
as can be seen from FIG. 2A, compared with the model group, there is no significant difference between the urine glucose amount of each dose group of the compound Geranium wilfordii and the urine glucose amount of db/db mice with the positive drug metformin; as can be seen in fig. 2B, compared to the model group, the compound geranium wilfordii high dose group significantly reduced creatinine content in urine of db/db diabetic mice, and had significant difference (. about.p <0.01), and no significant change was observed in the other groups.
In conclusion, the compound geranium wilfordii has the effects of improving the damaged kidney and the kidney function and has a good effect in treating diabetic nephropathy. Has the application prospect of being developed into the medicine for treating diabetic nephropathy.
Claims (1)
1. An application of compound herba Erodii seu Geranii in preparing medicine for treating diabetic nephropathy is provided.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101264122A (en) * | 2007-03-16 | 2008-09-17 | 中国医学科学院药物研究所 | Hypericum extract, its preparation method, its pharmaceutical composition and its application in treating diabetes |
| CN105560313A (en) * | 2016-01-27 | 2016-05-11 | 中国科学院新疆理化技术研究所 | Compound medicine prepared from Chinese St. John's wort herbs and carolina cranesbill herbs and used for treating diabetes and preparation method thereof |
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2021
- 2021-07-14 CN CN202110796438.5A patent/CN113350394A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101264122A (en) * | 2007-03-16 | 2008-09-17 | 中国医学科学院药物研究所 | Hypericum extract, its preparation method, its pharmaceutical composition and its application in treating diabetes |
| CN105560313A (en) * | 2016-01-27 | 2016-05-11 | 中国科学院新疆理化技术研究所 | Compound medicine prepared from Chinese St. John's wort herbs and carolina cranesbill herbs and used for treating diabetes and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 罗燕平等: "老鹳草素的研究进展", 《药物生物技术》 * |
| 郭炬亮等: "糙枝金丝桃药材提取方法研究", 《新疆医科大学学报》 * |
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Application publication date: 20210907 |