CN102935099A - Extractive capable of reducing insulin resistance as well as preparation method and application thereof - Google Patents
Extractive capable of reducing insulin resistance as well as preparation method and application thereof Download PDFInfo
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- CN102935099A CN102935099A CN2012105124656A CN201210512465A CN102935099A CN 102935099 A CN102935099 A CN 102935099A CN 2012105124656 A CN2012105124656 A CN 2012105124656A CN 201210512465 A CN201210512465 A CN 201210512465A CN 102935099 A CN102935099 A CN 102935099A
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- angelica keiskei
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- keiskei koidzumi
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Abstract
The invention provides a herbal mixture extractive of angelica keiskei and folium ginkgo capable of reducing insulin resistance. The extractive is prepared by extracting raw angelica keiskei and raw folium ginkgo based on weight ratio of 1:(0.1-10); and the extractive mainly comprises total flavone from angelica keiskei and total flavone from folium ginkgo. The invention also provides a preparation method of the extractive. The extractive shows remarkable hypoglycemic effect while being applied to a diabetic mice model and an insulin resistance rat model, and also can influence the tissue distribution and the function level of in-situ intestinal incretin secretory cells, and therefore, the insulin resistance can be treated; and the extractive can be developed and prepared into a medicine for reducing and treating insulin resistance, and thus the application of the extractive in preparation of a medicine for reducing the insulin resistance is provided.
Description
Technical field
The invention belongs to bio-pharmaceuticals and technical field of molecular biology, be specifically related to a kind of angelica keiskei koidzumi and Folium Ginkgo herbal mixture extract and in the application that improves insulin resistant and pharmaceutical preparation.
Background technology
Diabetes (diabetes) are the third-largest illness of harm humans health after cardiovascular disease and cancer as a kind of common endocrine metabolism disease.Insulin resistant (Insulin Resistance, IR) refer to that the target organ of insulin action is to the sensitivity decline of insulin action, the insulin that is normal dose produces a kind of state that is lower than normal biological effect, think at present, IR is not only the pathogenesis basis of type 2 diabetes mellitus, the main line that runs through especially multiple metabolism related diseases is the tie that connects them, is the common pathophysiological basis of these diseases.Though Chinese medicine is started late to the research of IR, research in recent years is gradually active, and becomes gradually the focus of Chinese medicine prevention diabetes scientific research.
Found that after deliberation the peptide matters of gastrointestinal endocrine cell secretion is to the regulation of secretion effect of insulin.These peptide matters are referred to as incretin, comprise gastric inhibitory polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1).GLP-1 is and secretion synthetic by the L cell of terminal jejunum, ileum and colon mainly, and GIP is by the enteral secretion K emiocytosis of duodenum and jejunum epimere.In recent years, have cell quantity, the neuroendocrine content of material that can affect when studies show that diabetes in gastrointestinal tract and the diffuse neuroendocrine system.Give the normal rat high fat diet, can cause the GIP supersecretion, and then stimulate the duodenum endocrine cell to the K cell differentiation, and relevant with insulin resistant.Clinical research finds that type 2 diabetes mellitus patient's GLP-1 secretion significantly reduces, and the promoting insulin secretion of GIP disappears, and pancreatotrophin's effect is impaired, and diabetic duration is played an important role.Normal person compares with blood glucose, and diabetics duodenum position GIP-IR cell, GIP/GLP-1 coexpression cell quantity all obviously increase.These researchs prove absolutely that the histology of secretin's secretory cell and changing function have been brought into play important function in diabetic duration.Therefore, the histology who manages to change secretin's secretory cell distributes and functional level has broad prospects in preparation improves the medicine of insulin resistant.
The massive epidemiology data shows that insulin resistant just can exist for many years, usually accompanied with obesity, hypertension, hyperlipemia before diabetes and cardiovascular disease incidence.But cause body weight further to increase after most medicines (insulin, sulphanylureas, glitazone) treatment.In addition, metformin can cause that lactic acid is piled up in the blood; The thiazolidinediones side effect is common with edema and fluid retention, may increase the weight of congestive heart failure; Exenatide is as a kind of novel synthetic incretin analog, can exciting GLP-1 receptor, produce blood sugar lowering and antidiabetic effect; Have data to show, this medicine all is a kind of potent Insulin-secreting agents in non-diabetic experimenter and type 2 diabetes mellitus patient; But it is as the artificial synthesis peptide, has certain immunogenicity and risk of hypoglycemia.
Diabetes and insulin resistant are as a kind of chronic disease, and Chinese medicine has great advantage and potentiality in this respect.The chemical compound that extracts in the plant has structure aspect biological activity clear and definite, and toxicity is little, acts on the characteristics such as lasting, remarkable.Flavone compound generally is distributed in the plant kingdom, and widely biological activity is arranged.Angelica keiskei koidzumi (angelica keiskei) Chinese another name is celery section archangel for BAZHANGQIN, seapeak Radix Ginseng and longevity greens/mustard green, and indomitable because of its vitality, priming leaf can be sent out sprouting tomorrow today, therefore named angelica keiskei koidzumi; Its main component is chalcone derivative and coumarin kind compound, and is remarkable in aspect effects such as antitumor, antioxidation, blood pressure lowering, blood sugar lowering.Folium Ginkgo (ginkgo leaves) has another name called Folium Ginkgo, and 1960's, West Germany namely began correlational study; Wherein contain multiple active ingredient, comprise flavone compound, bilobalide, oligomeric proanthocyanidin polyphenol etc., have the extensively pharmacological actions such as the blood cholesterol levels of reduction, control cerebral infarction, treatment bronchial asthma, free radical resisting peroxidating.Angelica keiskei koidzumi and Semen Ginkgo are medicine food dual purpose plant, as food or supplementary life-time service, show that it compares with chemicals and have higher safety, are fit to long-term taking.Therefore, its exploitation is become the medicine that improves insulin resistant, hypertension and hyperlipemia, treatment diabetes, have preferably application prospect.
Summary of the invention
The present invention seeks to the problem of improving the many side effect of insulin resistant medicine for existing, a kind of angelica keiskei koidzumi and Folium Ginkgo herbal mixture extract are provided and in the application that improves insulin resistant and pharmaceutical preparation, the histology who is specially the application fetches thing and affects secretin's secretory cell distributes and functional level, studies it and improves application in the insulin resistant medicine in preparation.
The present invention selects to be rich in angelica keiskei koidzumi and the Folium Ginkgo of different flavone compounds, mixes in varing proportions, extracts, and obtains to contain the flavone mixture of different proportion; Use diabetic mice, filter out the collaborative the strongest extract of blood sugar reducing function; Use insulin resistance rat, observe histology's distribution and functional level that the flavone mixture changes secretin's secretory cell, thereby improve insulin resistant, provide the new significant medicine of effect for improving the insulin resistant drug research.
It is a kind of that to improve extract of insulin resistant and preparation method thereof, use be to take following technical scheme to realize:
A kind of extract that can improve insulin resistant is characterized in that: adopt angelica keiskei koidzumi and Folium Ginkgo medicinal raw material to extract and form, wherein angelica keiskei koidzumi and Folium Ginkgo quality proportioning are 1:0.1 ~ 10.
Described angelica keiskei koidzumi and Folium Ginkgo quality proportioning are 1:1 ~ 10.
As a further improvement on the present invention, the said extracted thing is prepared as follows and forms: take by weighing angelica keiskei koidzumi and Folium Ginkgo by the quality proportioning, angelica keiskei koidzumi is mixed with Folium Ginkgo, add 60% ethanol, solid-liquid ratio is 1:15, soaks 24 hours under room temperature; Circumfluence method is extracted, and extraction conditions is as follows: 65 ℃ of temperature, extract each 4 hours 2 times; Decompress filter; Merging filtrate, Rotary Evaporators transpiring moisture, the concentrated extractum of making.
A kind of preparation method that can improve the extract of insulin resistant is characterized in that: take by weighing angelica keiskei koidzumi and Folium Ginkgo by the quality proportioning, angelica keiskei koidzumi is mixed with Folium Ginkgo, add 60% ethanol, solid-liquid ratio is 1:15, soaks 24 hours under room temperature; Circumfluence method is extracted, and extraction conditions is as follows: 65 ℃ of temperature, extract each 4 hours 2 times; Decompress filter; Merging filtrate, Rotary Evaporators transpiring moisture, the concentrated extractum of making.
Described a kind of extract that can improve insulin resistant is for the preparation of the application in the medicine that improves insulin resistant.
The described extract that can improve insulin resistant is used, it is characterized in that: the described medicine that improves insulin resistant is antitumor, antioxidation, blood pressure lowering, hypoglycemic medicine, or reduces blood cholesterol levels, control cerebral infarction, treatment bronchial asthma, the snperoxiaized medicine of free radical resisting.
Beneficial effect
Angelica keiskei koidzumi provided by the present invention and Folium Ginkgo herbal mixture extract can improve insulin resistant; Find that after deliberation the target site of this extract effect is secretin's secretory cell, distribute and functional level by the histology who affects secretin's secretory cell at body, thereby reach the purpose of improving insulin resistant.Extract can be prepared into especially oral drugs of a kind of medicine that improves insulin resistant.The treatment of insulin resistant is take Western medicine as main, and study hotspot is the secretin.Two kinds of Chinese herbal medicine that we will have blood sugar reducing function make up, and find that it improves new purposes and the novel mechanism of insulin resistant.
Description of drawings
The invention will be further described below with reference to accompanying drawing:
Fig. 1 represents rat liver pathological section figure (200 ╳)
Fig. 2 represents that extract is on the impact (X ± SD, N=8) of GLP-1, GIP level in the insulin resistance rat blood
The specific embodiment
Further specifying technical solution of the present invention below in conjunction with specific embodiment, is not the restriction to the technical program.
Biological material source among the present invention is as follows:
Angelica keiskei koidzumi and Folium Ginkgo are purchased from respectively Qingdao and Nanjing first sign pharmacy.
1 one kinds of preparations that can improve the extract of insulin resistant of embodiment
Take by weighing angelica keiskei koidzumi 100 g, Folium Ginkgo 10g by the quality proportioning, angelica keiskei koidzumi is mixed with Folium Ginkgo, add 60% ethanol (solid-liquid ratio is 1:15), under room temperature, soaked 24 hours; Circumfluence method is extracted (65 ℃ of temperature are extracted each 4 hours 2 times); Decompress filter; Merging filtrate, Rotary Evaporators transpiring moisture, the concentrated extractum of making.
2 one kinds of preparations that can improve the extract of insulin resistant of embodiment
Take by weighing angelica keiskei koidzumi 50 g, Folium Ginkgo 50g by the quality proportioning, angelica keiskei koidzumi is mixed with Folium Ginkgo, add 60% ethanol (solid-liquid ratio is 1:15), under room temperature, soaked 24 hours; Circumfluence method is extracted (65 ℃ of temperature are extracted each 4 hours 2 times); Decompress filter; Merging filtrate, Rotary Evaporators transpiring moisture, the concentrated extractum of making.
3 one kinds of preparations that can improve the extract of insulin resistant of embodiment
Take by weighing angelica keiskei koidzumi 10g, Semen Ginkgo 100g by the quality proportioning, angelica keiskei koidzumi is mixed with Folium Ginkgo, add 60% ethanol (solid-liquid ratio is 1:15), under room temperature, soaked 24 hours; Circumfluence method is extracted (65 ℃ of temperature are extracted each 4 hours 2 times); Decompress filter; Merging filtrate, Rotary Evaporators transpiring moisture, the concentrated extractum of making.
Embodiment 4 angelica keiskei koidzumis and Folium Ginkgo mixture extract are to the research of diabetic mice effect
Obtain three parts of angelica keiskei koidzumi and Folium Ginkgo mixture extracts with extracting method among the embodiment 1, the weight ratio of its angelica keiskei koidzumi and Folium Ginkgo is respectively 1:0.1(extract 1), 1:1(extract 2), 1:10(extract 3).
After water 12h is can't help in the male mice fasting, gavage 50% glucose in the 80mg/kg tail vein injection alloxan, 1-3h.Behind the 72h, the blood sampling of capillary tube eye rear vein beard, detecting animal blood glucose Xue Tang＞=11.1mmol/L with blood glucose meter is the modeling success, modeling success mice is divided into model group (M), metformin hydrochloride group (Y), extract 1(H1 at random), extract 2(H2), extract 3(H3), other gets ten normal mouses as Normal group (C).Be subjected to reagent mouse stomach administration 28.5ml/kg, amount to into identical crude drug dosage 10g/kg, positive controls: gavage 150mg/kg metformin hydrochloride, Normal group and model group give commensurability normal saline.Once a day, continuous 7 days.Fasting 8h before the last administration, the blood glucose value of 0.5h, 1h, 2h, 4h after fasting glucose (0h) and the last administration before the mensuration administration.
Experimental result shows that model group is compared with Normal group, and blood sugar level significantly raises, and shows the modeling success.Compare with model group, after 7 days, (0h) just can change blood sugar level by significance to extract before the last administration in administration, and 2h, 4h can change blood sugar level extremely significantly after the last administration, see Table 1.
Table 1 extract is on the impact (X ± S, n=12) of blood glucose in diabetic mice level
Compare * p＜0.05, * * p＜0.01, * * * p＜0.001 with model group; Compare ##p＜0.01 with matched group
Embodiment 5 angelica keiskei koidzumis and Folium Ginkgo mixture extract are to the research of insulin resistance rat effect
According to diabetic mice experimental result among the embodiment 2, select H3 group (angelica keiskei koidzumi Folium Ginkgo ratio is 1:1-10) research extract to the effect of insulin resistance rat, investigate from the following aspects respectively:
(1) extract is on the impact of insulin resistance rat fasting glucose (FSG), fasting insulin (FINS) and insulin resistant coefficient (ISI)
Male SD rat 160-180g, random packet is divided into Normal group (C) and model group (M).Matched group gives normal feedstuff, model group is fed and is given high lipid food (high lipid food prescription: 10% Adeps Sus domestica, 10% yolk powder, 20% sucrose, 2.5% cholesterol, 0.3% sodium cholate, 57.5% normal feedstuff), raise after 12 weeks with Oral Administration in Rats Glucose Tolerance and Insulin Resistance of Rats coefficient and estimate whether Cheng Mo of Insulin Resistance of Rats.The insulin resistance rat of Cheng Mo is divided at random: model group (M), positive controls (Y), flavone mixture high dose group (AH, crude drug dosage 10g/kg), flavone mixture low dose group (AL, crude drug dosage 5g/kg).Each is organized rat and continue to feed and to give high lipid food and continuous irrigation gastric solubleness matchmaker (CMC-Na) or 4 weeks of extract.Rat Septal curfew food be can't help water after 12 hours, and its fasting glucose (FSG) and fasting insulin value (FINS) are measured in the eyeground vein blood sampling, and calculated insulin resistant coefficient (ISI=FSG*FINS/22.5).
Experimental result shows (table 2), compares with model group, and gavage gives fasting glucose and the fasting insulin level that the high dose extract can significantly reduce insulin resistance rat, reduces the Insulin Resistance of Rats coefficient value.Illustrate that extract can effectively improve the Insulin Resistance of Rats symptom.
Table 2 extract is to insulin resistance rat fasting glucose (FSG)
The impact (X ± S, n=8) of fasting insulin (FINS) and insulin resistant coefficient (ISI)
Compare with model group,
*P＜0.05,
*P＜0.01,
* *P＜0.001; Compare with matched group,
##P＜0.01
(2) extract is on the impact of insulin resistance rat liver function
After administration finished, the rat sacrificed by exsanguination was got liver formalin and is fixed, and does pathological section, and did haematoxylin-Yihong (HE) dyeing.The result shows (Fig. 1): control rats hepatic tissue structural integrity, clear, and the lobules of liver structure is normal, and hepatocyte is arranged in the liver strand, radially distributes around central vein, and cell is polygon.During insulin resistance rat is-severe fatty liver, part fat drips and forms large cavity, nucleus is squeezed on one side, the lobules of liver structural deterioration, hepatocyte is arranged irregularity, and accompanies a large amount of swelling of liver cell, part is the balloon sample and becomes, all rats all can be seen inflammation in the lobule, and inflammatory cell is accompanied point-like or little focal necrosis take mononuclearcell as main.And after the administration, the hepar damnification situation makes moderate progress, and organizes HE dyeing to show that focal hepatic cell fattydegeneration is namely arranged, and is take vesicle as main Combination steatosis, and inflammatory cell infiltration in the lobule appears in the part.
(3) extract is on the impact of insulin resistance rat blood GLP-1, GIP level
After each organizes 4 weeks of administration, Rat Septal curfew food, survey on an empty stomach in the rat blood serum behind the GLP-1 and GIP content, behind the gastric infusion 2h more respectively gavage give 50% glucose 2g/kg rat, take a blood sample to the cold buffer liquid that fills EDTA to 30min, 60min rat optical fundus after the sugar, the centrifugal serum that gets, the content of incretin (GLP-1, GIP) in the survey rat blood serum.
Experimental result (Fig. 2) shows, compares with the C group, and the GIP level significantly raises during M group rat limosis; After giving sugared 30min and 60min, M group plasma concentration all continues to raise.Compare with the M group, AH group on an empty stomach GIP level descends, and behind sugared 30min and 60min, GIP all significantly descends, but still all is significantly higher than the C group.Compare with the C group, GLP-1 is without significant difference during M group rat limosis; After giving sugared 30min, the M group increases, and has significant difference; After giving sugared 60min, rat plasma concentration begins to descend, but still is higher than normal group.Compare with the M group, AH group GLP-1 on an empty stomach level slightly raises, but without significant difference; After giving sugared 30min and 60min, AH group GLP-1 all continues to raise.Above result shows that gavage gives extract, can regulate the incretin parasecretion of insulin resistance rat, helps to improve the Insulin Resistance of Rats symptom.
Claims (7)
1. extract that can improve insulin resistant is characterized in that: adopt angelica keiskei koidzumi and the extraction of Folium Ginkgo medicinal raw material to form, wherein angelica keiskei koidzumi and Folium Ginkgo quality proportioning are 1:0.1 ~ 10.
2. the extract that can improve insulin resistant according to claim 1, it is characterized in that: the quality proportioning of described angelica keiskei koidzumi and Folium Ginkgo is 1:1 ~ 10.
3. the extract that can improve insulin resistant according to claim 1, it is characterized in that: described angelica keiskei koidzumi and Folium Ginkgo extract main component are angelica keiskei koidzumi total flavones and Folium Ginkgo total flavones.
4. such as each described extract that can improve insulin resistant in the claim 1 ~ 3, it is characterized in that being prepared as follows and form: take by weighing angelica keiskei koidzumi and Folium Ginkgo by the quality proportioning, angelica keiskei koidzumi is mixed with Folium Ginkgo, add 60% ethanol, solid-liquid ratio is 1:15, soaks 24 hours under room temperature; Circumfluence method is extracted, and extraction conditions is as follows: 65 ℃ of temperature, extract each 4 hours 2 times; Decompress filter; Merging filtrate, Rotary Evaporators transpiring moisture, the concentrated extractum of making.
5. each the described preparation method that can improve the extract of insulin resistant in the claim 1 ~ 3, it is characterized in that: take by weighing angelica keiskei koidzumi and Folium Ginkgo by the quality proportioning, angelica keiskei koidzumi is mixed with Folium Ginkgo, add 60% ethanol, solid-liquid ratio is 1:15, soaks 24 hours under room temperature; Circumfluence method is extracted, and extraction conditions is as follows: 65 ℃ of temperature, extract each 4 hours 2 times; Decompress filter; Merging filtrate, Rotary Evaporators transpiring moisture, the concentrated extractum of making.
In the claim 1 ~ 3 each described extract that can improve insulin resistant for the preparation of the application in the medicine that improves insulin resistant.
7. the application of extract as claimed in claim 7, it is characterized in that: the described medicine that improves insulin resistant is antitumor, antioxidation, blood pressure lowering, hypoglycemic medicine, or reduces blood cholesterol levels, control coronary heart diseases and angina pectoris, cerebral infarction, treatment bronchial asthma, the snperoxiaized medicine of free radical resisting.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103734422A (en) * | 2013-12-30 | 2014-04-23 | 徐州绿之野生物食品有限公司 | Ashitaba ginkgo tea |
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| JP2001252044A (en) * | 2000-03-15 | 2001-09-18 | Healthy Shokuhin Kk | Medicinal herb dish prepared with five main nutrient- mixed food |
| JP2006025630A (en) * | 2004-07-13 | 2006-02-02 | Japan Organo Co Ltd | Functional food |
| JP2009256270A (en) * | 2008-04-18 | 2009-11-05 | Maruzen Pharmaceut Co Ltd | Insulin-like growth factor-1 expression promoting agent |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001252044A (en) * | 2000-03-15 | 2001-09-18 | Healthy Shokuhin Kk | Medicinal herb dish prepared with five main nutrient- mixed food |
| JP2006025630A (en) * | 2004-07-13 | 2006-02-02 | Japan Organo Co Ltd | Functional food |
| JP2009256270A (en) * | 2008-04-18 | 2009-11-05 | Maruzen Pharmaceut Co Ltd | Insulin-like growth factor-1 expression promoting agent |
Non-Patent Citations (2)
| Title |
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| 周先丽等: "明日叶的化学成分", 《中国实验方剂学杂志》, vol. 18, no. 3, 29 February 2012 (2012-02-29), pages 103 - 105 * |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103734422A (en) * | 2013-12-30 | 2014-04-23 | 徐州绿之野生物食品有限公司 | Ashitaba ginkgo tea |
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