Application of rubia yunnanensis and rubia yunnanensis extract in preparation of medicine for preventing and / or treating carotid atherosclerosis
By using the extract of glutinous ginseng alcohol, the problem of the failure of the prior art to effectively prevent and treat carotid atherosclerosis was solved, and the blood lipids were reduced, lipid accumulation was inhibited, endothelial cell damage was reduced, and the PI3K/AKT signaling pathway activity was improved, which significantly improved the pathological state of carotid atherosclerosis.
Patent Information
- Application Number
- CN202311061489.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-08-22
- Publication Date
- 2025-02-25
AI Technical Summary
The prior art has failed to effectively utilize the potential of ginseng and its extracts in the prevention and treatment of carotid atherosclerosis.
The small red ginseng alcohol extract was prepared by using organic solvent extracts of small red ginseng, especially ethanol extracts, and administered by oral routes to reduce blood lipid levels, inhibit carotid lipid accumulation, reduce endothelial cell damage, reduce collagen fiber content and inhibit elastic fiber accumulation. Little Red Ginseng Alcohol Extract improves carotid atherosclerosis induced by high-fat diets by upregulating the PI3K/AKT signaling pathway.
The extract of ginseng alcohol significantly reduced the levels of cholesterol, triglycerides and low-density lipoprotein-cholesterol in the serum, while also increased the levels of high-density lipoprotein cholesterol, reduced endothelial cell damage, inhibited the accumulation of lipids, collagen fibers and elastic fibers, and effectively improved carotid atherosclerosis.
Smart Images
Figure 00000000_0002_ABST 
Figure 00000000_0001_ABST 
Figure 00000000_0003_ABST 
Figure 00000000_0000_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of ethnic medicines, and particularly relates to use of small red ginseng and an extract thereof in preparing a medicine for preventing and / or treating carotid atherosclerosis. Background Art
[0002] Atherosclerosis (AS) is a chronic progressive vascular wall disease, which is mainly composed of plaques formed by lipid deposition under the intima of large and medium-sized arteries and fibers formed by local inflammatory reactions in blood vessels. Plaques gradually accumulate, causing arteries to become narrow and elastic. With the continuous improvement of people's living standards and changes in living habits, the incidence and mortality of cardiovascular diseases based on AS are increasing. About 16 million people die from cardiovascular diseases every year worldwide, which is the disease with the highest mortality rate in the world. With the passage of time and in-depth research, it has been recognized that AS is a dynamic process. Lipid metabolism disorders are the initiating factors of AS, which in turn cause damage to endothelial cells and eventually form atherosclerotic plaques.
[0003] It is well known that abnormal lipid metabolism and endothelial cell damage play an important role in the occurrence and development of AS. Abnormal lipid metabolism is mainly the increase in the levels of lipids and some lipoproteins in plasma, which in turn causes damage to the vascular endothelium, leading to the accumulation of various adhesion factors on endothelial cells, weakening endothelial cell function, causing inflammatory reactions and ultimately forming AS. The homeostasis of the vascular environment depends on the integrity of vascular endothelial cells and their normal function. Therefore, regulating lipid metabolism disorders and protecting endothelial cells have important clinical significance for anti-atherosclerosis.
[0004] Yi medicine small red ginseng is a valuable traditional Chinese medicine. It is the dried root and rhizome of Rubia yunnanensis Diels (RY), a plant of the Rubiaceae family. It is a unique ethnic medicine in Yunnan, China. Studies have shown that small red ginseng has pharmacological effects such as anti-myocardial ischemia, anti-oxidation, and anti-platelet. It has been recorded in the "Southern Yunnan Materia Medica" that it has been used to treat gastrointestinal diseases, trauma, and irregular menstruation for hundreds of years.
[0005] There are currently no reports on the involvement of Rhizoma Coptidis in carotid atherosclerosis. Summary of the invention
[0006] The object of the present invention is to provide a use of small red ginseng and an extract thereof in preparing a drug for preventing and / or treating carotid atherosclerosis.
[0007] The present invention provides use of small red ginseng and an extract thereof in preparing a medicine for preventing and / or treating atherosclerosis.
[0008] Furthermore, the atherosclerosis is carotid atherosclerosis.
[0009] Furthermore, the drug is a drug that reduces triglycerides, cholesterol and low-density lipoprotein-cholesterol in blood lipids and increases high-density lipoprotein cholesterol levels.
[0010] Furthermore, the drug is a drug that reduces collagen fiber content and inhibits elastic fiber accumulation;
[0011] Furthermore, the drug is a drug for inhibiting arterial lipid accumulation.
[0012] Furthermore, the drug is a drug that reduces endothelial cell damage.
[0013] Furthermore, the drug is a drug that upregulates the PI3K / AKT signaling pathway.
[0014] Furthermore, the small red ginseng extract is an organic solvent extract of small red ginseng, and preferably, the small red ginseng extract is an ethanol extract of small red ginseng.
[0015] Furthermore, the preparation method of the organic solvent extract of small red ginseng is: take small red ginseng, grind it into powder, soak and extract it with 8-12 times (v / w, ml / g) 80-99% organic solvent, heat and reflux, extract (3-5) times, and obtain small red ginseng extract concentrate;
[0016] Preferably, the preparation method of the organic solvent extract of small red ginseng is: take small red ginseng, grind it into powder, extract it with 10 times (v / w, ml / g) 95% organic solvent at warm temperature, heat and reflux, repeat the extraction 4 times to obtain small red ginseng extract, freeze-dry the small red ginseng extract to obtain freeze-dried powder of small red ginseng extract;
[0017] Preferably, the organic solvent is ethanol; preferably, the heating reflux temperature is 60°C, and the freeze-drying temperature is -80°C.
[0018] Furthermore, it is an oral preparation or injection preparation prepared by using the aforementioned small red ginseng or small red ginseng extract as an active ingredient and adding pharmaceutically acceptable excipients or auxiliary ingredients;
[0019] The oral preparations include but are not limited to tablets, granules, capsules, pills, powders, suspensions or solutions.
[0020] The present invention provides a use of an alcohol extract of a Yi medicine, red ginseng, in preparing a drug for treating carotid atherosclerosis. The present invention establishes a model by feeding ApoE mice with a high-fat diet for 12 weeks, and compares the modeling with the alcohol extract of red ginseng. It is found that the alcohol extract of red ginseng can reduce blood lipid levels, inhibit carotid lipid accumulation, reduce endothelial cell damage, reduce collagen fiber content and inhibit elastic fiber accumulation. The alcohol extract of red ginseng can effectively improve carotid atherosclerosis induced by a high-fat diet by upregulating the PI3K / AKT signaling pathway. In general, red ginseng is a promising anti-carotid atherosclerosis drug.
[0021] Obviously, according to the above contents of the present invention, in accordance with common technical knowledge and customary means in the art, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change may be made.
[0022] The above contents of the present invention are further described in detail below through specific implementation methods in the form of embodiments. However, this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. All technologies realized based on the above contents of the present invention belong to the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS
[0023] Figure 1 Lipid levels in each group, (A) cholesterol (TC) level, (B) triglyceride (TG) level, (C) low-density lipoprotein cholesterol (LDL-C) level, (D) high-density lipoprotein cholesterol (HDL-C level), comparison of blood lipid levels in four different experimental groups. Data are expressed as mean ± standard deviation (n = 8 mice / group). **** P<0.0001vs.controls. # p<0.05, ## p<0.01, ### p<0.001 and #### P < 0.0001 vs. HFD;
[0024] Figure 2 HE staining results of carotid artery in each group, A: blank control group, B: model group, C: high-dose group of ginseng alcohol, D: low-dose group of ginseng alcohol;
[0025] Figure 3 Masson staining results of each group. A: blank control group, B: model group, C: high-dose group of ginseng alcohol, D: low-dose group of ginseng alcohol, E: quantitative analysis of carotid artery collagen area. Data are expressed as mean ± standard deviation (n = 3 mice / group). **** P<0.0001vs.controls. #### P<0.0001vs.MOD
[0026] Figure 4 Oil red O staining results of carotid artery in each group, A: blank control group, B: model group, C: high-dose group of ginseng alcohol, D: low-dose group of ginseng alcohol; E: ratio of carotid artery lipid red staining area. Data are expressed as mean ± standard deviation (n = 3 mice / group). ****P < 0.0001 vs. controls. ####P < 0.0001 vs. MOD
[0027] Figure 5 Carotid artery EVG staining results A: blank control group, B: model group, C: high-dose ginseng alcohol group, D: low-dose ginseng alcohol group.
[0028] Figure 6 Expression of proteins AKT, PI3K, p-PI3K and p-AKT in four different experimental groups; (A) Representative Western blot quantitative analysis of PI3K, AKT and phosphorylated p-PI3K and p-AKT (B) p-PI3K / PI3K protein expression, (C) p-AKT / AKT expression, (D) p-PI3K expression, (E) p-AKT expression; Figure data are expressed as mean ± standard deviation (n = 3 mice / group). *P < 0.05 vs. controls and ****P < 0.0001 vs. controls. ####P < 0.0001 vs. MOD. AKT, phosphatidylinositol 3-kinase; PI3K, protein kinase B. DETAILED DESCRIPTION
[0029] The raw materials and equipment used in the present invention are all known products, which are obtained by purchasing commercially available products.
[0030] Rubia yunnanensis (Franch.) was purchased from Yunnan Huide Pharmaceutical Co., Ltd., China) Example 1. Ethanol extract of Yi medicine Rubia yunnanensis of the present invention and its test
[0031] 1. Experimental Methods
[0032] (I) Preparation of red ginseng ethanol extract and HPLC analysis of its main components
[0033] Rubia yunnanensis (Franch.) was purchased from Yunnan Huide Pharmaceutical Co., Ltd.
[0034] Put the small red ginseng into a powder machine and crush it into powder by roller pressing. Soak the small red ginseng powder in 95% ethanol for 24 hours, stir it every 3 hours, and after soaking, heat it under reflux at 60°C using a rotary evaporator. Repeat the extraction four times to obtain the 95% ethanol extract of small red ginseng. Take an appropriate amount of the 95% ethanol extract of small red ginseng and put it into a beaker and place it in a -80°C freeze dryer to freeze-dry it into powder.
[0036] (II) Animal experiments
[0037] 1. Experimental Animals
[0038] A total of 24 male C57BL / 6J mice (age, 8 weeks; weight 18-22 g) were housed in stainless steel-top plastic-bottom cages with daily light exposure of about 12 h, temperature 20-24 °C, and humidity of about 50%. They had free access to water and food. All experiments were approved by the Animal Ethics Committee of Yunnan University of Traditional Chinese Medicine and met the Animal Ethics Review Standards of Yunnan University of Traditional Chinese Medicine (Kunming, China; Lot No.: R-062022053).
[0039] 2. Animal grouping
[0040] At present, studies have been conducted to evaluate the efficacy and mechanism of AS disease by constructing an AS mouse model. The present invention uses ApoE- / - mice to induce a high-fat diet to establish a carotid atherosclerosis mouse model (AS mouse model).
[0041] After 1 week of adaptive feeding of normal diet, the mice were randomly divided into 4 groups, with 6 mice in each group.
[0042] i) Control group (CON): fed with normal diet for 12 weeks;
[0043] ii) Model group high-fat diabetic (MOD): fed with a high-fat diet for 12 weeks;
[0044] iii) High-dose red ginseng alcohol extract group (RY+H): fed with a high-fat diet for 12 weeks, and orally administered red ginseng alcohol extract (2.5 g / kg) every day, at a volume of 0.1 ml / 10 g body weight;
[0045] iv) Low-dose red ginseng ethanol extract group (RY+L): The mice were fed a high-fat diet for 12 weeks and simultaneously orally administered red ginseng ethanol extract (1.25 g / kg) at a volume of 0.1 ml / 10 g body weight every day.
[0046] The control group and the model group were orally administered with an equal volume of normal saline.
[0047] 3. Blood lipid level test
[0048] Lipid metabolism disorder is the initiating factor in the development of carotid atherosclerosis and is extremely important in the formation of carotid atherosclerosis. Lipids include triglycerides (TG), cholesterol (TC) and its esters, phospholipids and glycolipids. When TG increases, it will cause damage to vascular endothelial cell function, vigorous lipid metabolism, excessive production of oxygen free radicals, promote the expression of adhesion molecules, so that the body cannot clear them in time, causing oxidative damage, and promote the formation of foam cells and induce inflammatory reactions, aggravating the occurrence and development of AS. Elevated TC can promote the adhesion of leukocytes and the aggregation of platelets, cause the release of growth factors and the infiltration of monocytes, promote the proliferation of smooth muscle cells, accelerate the entry of smooth muscle cells into the intima, and promote the production of collagen fibers, and also change fat plaques into fibrous plaques. Blood lipids can combine with apolipoproteins to form lipoproteins, which is the main form of blood lipids in the body. Most TC combines with low-density lipoproteins (LDL) to form low-density lipoprotein-cholesterol (LDL-C). When LDL-C is too high, it is related to inflammation and lipid accumulation, which can promote plaque formation and cause a large number of vascular smooth muscle cells to proliferate. High-density lipoprotein cholesterol (HDL-C) can reversely transport TC to the liver to reduce the TC content in the body. When the HDL-C level is significantly reduced, the reverse transport of TC will be inhibited, the TC content in the body will increase, and the risk of AS will be increased. The present invention detected TC, TG, LDL-C, and HDL-C in carotid atherosclerosis model mice.
[0049] Mice were anesthetized by intraperitoneal injection of sodium pentobarbital (35 mg / kg), blood samples were collected, and serum was obtained by centrifugation at 4°C, 3500r for 15 min. Then, TC, TG, LDL-C, and HDL-C were measured using the kit according to the instructions.
[0050] 4. Histological examination of carotid atherosclerosis
[0051] (1) HE staining
[0052] First, the mice were killed by dislocating the cervical vertebra under anesthesia, and the carotid artery was removed from the mouse neck, and the adipose tissue was cut off. The carotid artery was fixed in 4% paraformaldehyde at room temperature for 24 h, and the tissue was dehydrated using a series of ethanol with increasing concentrations. After washing with xylene, the paraffin-embedded carotid artery was transversely cut into slices with a thickness of about 4 μm, stained with hematoxylin for 5 min, and eosin for 5 min, and finally the tissue condition of the carotid artery was examined using an optical microscope (magnification, ×40).
[0053] (2) Masson staining
[0054] The fixed carotid artery was dehydrated using a series of sucrose solutions with increasing concentrations. The OCT-embedded carotid artery was transversely cut into slices of about 8 μm thick, and the slices were immersed in Masson A solution overnight, rinsed with tap water, and then immersed in a dye solution mixed with Masson B and Masson C in equal proportions for 1 min, differentiated with differentiation solution for a few seconds, and then immersed in Masson D solution for 6 min. The slices were rinsed with tap water and then immersed in Masson E solution for 1 min. Without rinsing, the slices were immersed in Masson F solution for 30 s. Finally, the collagen fibers of the carotid artery were examined using an optical microscope (magnification, ×40).
[0055] (3) Oil red staining
[0056] The carotid arteries of OCT embedded sections were immersed in Oil Red O staining solution for 10 minutes (protected from light), then differentiated in 60% isopropanol twice (2s and 5s), and then rinsed in pure water twice for 10s each. Then the sections were immersed in hematoxylin staining solution for 5 minutes, rinsed in pure water 3 times (5s, 10s, 30s), differentiated for 8s, washed twice with distilled water for 10s each, blued for 1s with blueing solution, and then immersed in tap water for 2 times (5s, 10s), and finally the lipid accumulation of the carotid artery was examined using an optical microscope (magnification, ×40).
[0057] (4) VERHOEFF'S VAN GIESON Dyeing
[0058] The OCT-embedded carotid artery sections were placed in EVG dye solution for 5 minutes. EVG dye solution B was diluted 1 times and rinsed with tap water after differentiation until the elastic fibers turned purple-black. Then EVG dye solution E: EVG dye solution D = 9:1 were mixed into VG dye solution and immersed for 3 minutes. Finally, an optical microscope (magnification, ×40) was used to examine the elastic fibers and collagen fibers of the carotid artery.
[0059] 5. Western Blot Analysis
[0060] Western blotting was used to detect the protein levels of P-AKT and p-PI3K in carotid artery tissues.
[0061] The mouse carotid artery tissue was fully lysed using RIPA lysis buffer (No. P0013 C; Beyotime Biotechnology Institute), and the lysate was centrifuged at 4°C, 12000r for 5 min, and the supernatant was collected into a pre-cooled Eppendorf tube.
[0062] Then, the protein was analyzed by SDS-PAGE on a 10% gel (Criterion TM ; Trans- The proteins were then transferred to a PVDF membrane (IPFL85R; Millipore, Schwalbach, Germany) and the membrane was blocked in 5% skim milk at room temperature for 2 hours. After blocking, TBST buffer (0.1% Tween; QN 1236; Beijing Bio-Rad Technology Co., Ltd.) was added. Subsequently, the membranes were incubated with the following primary antibodies overnight at 4°C: anti-PI3K (1:1,000; catalog number 4257, Cell Signaling Technology, Boston, USA), anti-p-PI3k (1:1,000; 4228; Cell Signaling Technology, Boston, USA), and anti-AKT (1:1,000; 9272; Cell Signaling Technology, Boston, USA), p-AKT (1:1,000; 9271; Cell Signaling Technology, Boston, USA), and β-actin (1:1,000; 4967; Cell Signaling Technology, Boston, USA).
[0063] After overnight incubation with the primary antibody, the membrane was washed three times with TBST. The membrane was incubated with goat anti-rabbit IgG secondary antibody (1:5,000; catalog number ab 6721; Abcam) for 1 h at room temperature and washed three times with TBST. Finally, chemiluminescent reagent (ECL; catalog number A38555; Cell Signaling Technology, Boston, USA) was added to detect the presence of chromatin in the Bio-Rad ChemiDoc TM Immunoreactive bands were observed using an XRS gel imaging system (Bio-Rad Laboratories, Ltd.). Image Lab TM V4.0 software (Bio-Rad Laboratories, Ltd.) was used to detect optical signals and quantify protein levels.
[0064] All experimental groups were divided into three parallel groups, and the experiments were repeated three times.
[0065] 6. Statistical analysis
[0066] GraphPad Prism 8 software was used to process the experimental data. The quantitative data were expressed as mean ± standard deviation (x ± SD), and the data were analyzed by one-way ANOVA. P < 0.05 was considered statistically significant.
[0067] 2. Experimental Results
[0068] 1. Blood lipid levels of mice in each group
[0069] The blood lipid levels of mice in each group were Figure 1 Compared with the control group, the TC, TG, and LDL-C levels in the model group were significantly increased, while the HDL-C level was significantly decreased. Compared with the model group, the high-dose red ginseng alcohol extract group reduced serum TC (p<0.001), TG (p<0.01), and LDL-C (p<0.0001) levels, and significantly increased HDL-C levels (p<0.01). The low-dose red ginseng alcohol extract group significantly reduced serum TC (p<0.05), TG, and LDL-C levels, and increased HDL-C levels. Among them, the high-dose red ginseng alcohol extract group had a significant effect.
[0070] The experimental results show that the alcohol extract of red ginseng can reduce the levels of TC, TG, and LDL-C, while increasing the level of HDL-C, which can improve endothelial cell damage and reduce the accumulation of lipids, collagen fibers, and elastic fibers. It proves that the alcohol extract of red ginseng can regulate lipid metabolism disorders in mice with carotid atherosclerosis model and improve the condition of plaques in the carotid artery.
[0071] 2. Histological analysis of carotid artery
[0072] (1) HE staining of carotid artery
[0073] HE staining results showed that the vascular structure of the control group was intact, smooth, and clearly layered, without obvious damage or obvious stenosis of the lumen. However, the vascular endothelium of the model group was damaged, the structure and morphology were disordered, the plaque area was large, the number of lipid nuclei in the plaque was large, the lumen was severely narrowed, the endothelial cells were irregularly arranged, and a large number of atherosclerotic plaques were formed, indicating that carotid atherosclerosis would cause serious endothelial cell damage during its occurrence, and the high and low doses of small red ginseng groups could significantly reduce endothelial cell damage.
[0074] Compared with the model group, the carotid artery vascular lesions in the high- and low-dose Rhizoma Ginseng groups were significantly alleviated.
[0075] (2) Masson
[0076] After Masson staining, collagen fibers appeared blue and smooth muscle cells appeared red. The blue staining expression of the aorta in the model group was significantly higher than that in the normal group, and the degree of fibrosis was significantly increased (p<0.0001). Compared with the model group, the collagen fiber content in the high and low dose groups of small red ginseng was significantly reduced (p<0.0001).
[0077] (3) Oil Red O staining results
[0078] Oil red O staining results showed that ( Figure 4 ), there was no lipid deposition in the carotid artery of the blank control group; there was a large amount of lipid deposition and atherosclerotic plaques in the carotid artery of the model group (p<0.0001); compared with the model group, the carotid artery plaque area of the high- and low-dose groups of Small Red Ginseng was significantly reduced (p<0.0001).
[0079] The experimental results showed that the alcohol extract of red ginseng could significantly inhibit lipid accumulation in the carotid artery, and the high-dose alcohol extract of red ginseng group had a higher inhibitory effect on lipid accumulation in the carotid artery than the low-dose group.
[0080] (4) EVG staining results
[0081] EVG staining results showed that the elastic fibers in the vascular endothelium of the blank control group were smooth and intact, without elastic fibers and collagen fibers aggregation; in the model group, a large number of elastic fibers and collagen fibers aggregated in the vascular endothelium, and the elastic fibers in the vascular endothelium became thinner; the elastic fiber and collagen fiber aggregation in the high and low dose groups of small red ginseng were significantly reduced compared with the model group, improving the thinning of the elastic fibers in the vascular endothelium.
[0082] The experimental results showed that the alcohol extract of red ginseng could significantly inhibit the aggregation of elastic fibers and improve the thinning of elastic fibers in the inner wall of blood vessels; the elastic fiber aggregation in the high and low dose groups of red ginseng was less than that in the model group, and the high dose of red ginseng alcohol extract group had a higher inhibitory effect on elastic fiber aggregation than the low dose group.
[0083] 4. Western blot analysis results (PI3K / AKT signaling pathway protein expression results)
[0084] The phosphatidylinositol 3-kinase / protein kinase B (PI3K / AKT) signaling pathway is a classic signaling pathway that is widely present in organisms. It is currently known that this pathway is closely related to atherosclerosis. Studies have confirmed that upregulating the activity of the PI3K / AKT signaling pathway can promote vascular regeneration, improve and repair heart damage. In her research, Zhang Wenwen found that the traditional Chinese medicine Astragalus compound may protect endothelial function by activating the PI3K / AKT signaling pathway and reducing the levels of endothelial injury factors and inflammatory factors in rat serum.
[0085] Compared with the blank control group, the expression of p-PI3K (p<0.0001) and p-AKT (p<0.05) proteins in the carotid artery tissue of the model group was significantly reduced; that is, a high-fat diet can induce significant abnormal blood lipids in ApoE- / - mice and induce severe pathological changes in carotid atherosclerosis, with reduced P-PI3K and P-AKT protein levels, and decreased P-PI3K / PI3K and P-AKT / AKT ( Figure 6 ), indicating that the phosphorylation process of PI3K and Akt is inhibited in the process of carotid atherosclerosis, suggesting that the activity of PI3K / AKT signaling pathway is inhibited.
[0086] Compared with the model group, the expression of p-PI3K (p<0.0001) and p-AKT proteins in the carotid artery tissue of the high- and low-dose red ginseng groups was significantly increased. The ratios of P-PI3K / PI3K and P-AKT / AKT were significantly increased compared with the model group ( Figure 6 B, Figure 6 C), indicating that the ethanol extract of small red ginseng can improve the phosphorylation process of PI3K and AKT in mice with carotid atherosclerosis model, and upregulate the activity of PI3K / AKT signaling pathway. This shows that the ethanol extract of small red ginseng can upregulate the phosphorylation process of PI3K and AKT in mice with carotid atherosclerosis model, and then upregulate the activity of PI3K / AKT and P-PI3K / PI3K signaling pathways, that is, the ethanol extract of small red ginseng can improve carotid atherosclerosis and alleviate endothelial cell damage.
[0087] In ApoE- / - mice fed with a high-fat diet for 12 weeks, EVG staining results showed that the alcohol extract of red ginseng could improve elastic fiber aggregation. This may be because the alcohol extract of red ginseng lowered blood lipid levels and alleviated endothelial damage to inhibit the occurrence and development of AS. This process may be achieved by upregulating the PI3K / AKT signaling pathway, indicating that the alcohol extract of red ginseng can effectively improve endothelial damage.
[0088] In summary, the present invention provides a use of an alcohol extract of a Yi medicine, red ginseng, in the preparation of a therapeutic drug for carotid atherosclerosis. The present invention establishes a model by feeding ApoE mice with a high-fat diet for 12 weeks, and compares the modeling with the alcohol extract of red ginseng. It is found that the alcohol extract of red ginseng can reduce blood lipid levels, inhibit carotid lipid accumulation, reduce endothelial cell damage, reduce collagen fiber content and inhibit elastic fiber accumulation. The alcohol extract of red ginseng can effectively improve carotid atherosclerosis by upregulating the PI3K / AKT signaling pathway. In general, red ginseng and its extract are a promising anti-carotid atherosclerosis therapeutic drug.
Claims
1. Use of small red ginseng and its extract in preparing a medicine for preventing and / or treating atherosclerosis.
2. The use according to claim 1, characterized in that: The atherosclerosis is carotid atherosclerosis.
3. The use according to claim 1 or 2, characterized in that: The drug is a drug that lowers triglycerides, cholesterol and low-density lipoprotein-cholesterol in blood lipids and increases high-density lipoprotein cholesterol levels.
4. The use according to claim 1 or 2, characterized in that: The drug is a drug that reduces the content of collagen fibers and inhibits the accumulation of elastic fibers.
5. The use according to claim 1 or 2, characterized in that: The drug is a drug that inhibits arterial lipid accumulation.
6. The use according to claim 1 or 2, characterized in that: The drug is a drug that reduces endothelial cell damage.
7. The use according to claim 1 or 2, characterized in that: The drug is a drug that upregulates the PI3K / AKT signaling pathway.
8. The use according to any one of claims 1 to 7, characterized in that: The small red ginseng extract is an organic solvent extract of small red ginseng, preferably, the small red ginseng extract is an ethanol extract of small red ginseng.
9. The use according to any one of claims 1 to 7, characterized in that: The preparation method of the organic solvent extract of small red ginseng is as follows: taking small red ginseng, grinding it into powder, soaking and extracting it with 8-12 times (v / w, ml / g) 80-99% organic solvent, heating and refluxing, extracting (3-5) times, and obtaining the small red ginseng extract concentrate; Preferably, the preparation method of the organic solvent extract of small red ginseng is: take small red ginseng, grind it into powder, extract it with 10 times (v / w, ml / g) 95% organic solvent at warm temperature, heat and reflux, repeat the extraction 4 times to obtain small red ginseng extract, freeze-dry the small red ginseng extract to obtain freeze-dried powder of small red ginseng extract; Preferably, the organic solvent is ethanol; preferably, the heating reflux temperature is 60°C, and the freeze-drying temperature is -80°C.
10. A composition for preventing and / or treating carotid atherosclerosis, characterized in that: It is an oral preparation or injection preparation prepared by using the small red ginseng or small red ginseng extract as claimed in claim 1 as an active ingredient and adding pharmaceutically acceptable excipients or auxiliary ingredients; The oral preparations include but are not limited to tablets, granules, capsules, pills, powders, suspensions or solutions.