A composition and its use in inhibiting HMG-CoA reductase activity and lowering blood lipids

Abstract

The present application relates to the technical field of functional preparation, and particularly relates to a composition and application thereof in inhibiting HMG-CoA reductase activity and reducing blood lipid. The composition comprises steviol glycosides and lariciresinol in a mass ratio of 1300-1400:1. The composition in the specific ratio can achieve synergistic effect, significantly inhibit HMG-CoA reductase activity, reduce serum total cholesterol and low-density lipoprotein cholesterol, and increase high-density lipoprotein cholesterol. The effect is significantly better than that of a single component. The raw materials of the composition are all natural active ingredients, the safety is high, the effect is better, and the composition has a wide application prospect.

Description

Technical Field

[0001] This invention relates to the field of functional formulation technology, and in particular to a composition and its application in inhibiting HMG-CoA reductase activity and lowering blood lipids. Background Technology

[0002] Hyperlipidemia, also known as hyperlipidemia, is a metabolic disease characterized by abnormally high levels of lipids in the blood. Clinically, it is mainly divided into three categories: high triglyceride type, high cholesterol type, and mixed type.

[0003] Currently available cholesterol-lowering drugs, such as statins, have adverse reactions such as abnormal liver function and muscle damage, and long-term medication adherence is poor. Although PCSK9 inhibitors have significant lipid-lowering effects, their injection administration method and relatively high treatment costs limit their widespread use. Ezetimibe has limited lipid-lowering strength when used alone and is mainly used as an adjunct therapy for statins.

[0004] Therefore, it is of great significance to develop a natural, effective, and safe cholesterol-lowering product. Summary of the Invention

[0005] This invention provides a composition and its application in inhibiting HMG-CoA reductase activity and lowering blood lipids.

[0006] In a first aspect, the present invention provides a composition comprising stevia polyphenols and larch resinol in a mass ratio of 1300-1400:1.

[0007] Preferably, in the composition, the mass ratio of stevia polyphenols to larch resinol is 1300-1350:1.

[0008] Stevia polyphenols, mainly including chlorogenic acid, isochlorogenic acid, caffeic acid and their derivatives, possess antioxidant and anti-inflammatory biological activities. Larixol is a natural lignan compound widely found in plants such as larch, flaxseed, and sesame, and possesses antioxidant, anti-inflammatory, and anti-tumor biological activities.

[0009] 3-Hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) is the rate-limiting enzyme in the cholesterol synthesis pathway in the human body. It catalyzes the conversion of HMG-CoA to mevalonic acid in cholesterol synthesis and determines the amount of cholesterol produced subsequently.

[0010] This invention unexpectedly discovered that combining stevia polyphenols and larvicides within the aforementioned ratio range resulted in a synergistic effect, significantly reducing HMG-CoA reductase activity and thus lowering cholesterol synthesis, with effects markedly superior to those of the individual components. During the research and development process, other grape polyphenols with similar effects to stevia polyphenols, as well as other larvicides, were also tested. It was found that replacing these components disrupted the synergistic effect, resulting in a significantly reduced cholesterol-lowering effect of the resulting composition.

[0011] In a second aspect, the present invention provides the use of the composition described in the first aspect in the preparation of products for the prevention and / or treatment of hyperlipidemia.

[0012] Preferably, the product is used for at least one of the following: lowering total cholesterol, lowering LDL cholesterol, and raising HDL cholesterol.

[0013] Thirdly, the present invention provides the use of the composition described in the first aspect in the preparation of products that help maintain healthy blood lipid levels.

[0014] Preferably, the product is used for at least one of the following: lowering total cholesterol, lowering LDL cholesterol, and raising HDL cholesterol.

[0015] Fourthly, the present invention provides the use of the composition described in the first aspect in the preparation of a product that inhibits HMG-CoA reductase activity.

[0016] In the above applications, the product is either food or medicine. The food includes health foods.

[0017] Fifthly, the present invention provides a product comprising the composition described in the first aspect; Preferably, the product has at least one of the following effects: (1) Inhibits HMG-CoA reductase activity; (2) Lower total cholesterol and / or LDL cholesterol levels; (3) Increase high-density lipoprotein cholesterol levels.

[0018] (4) Prevention and / or treatment of hyperlipidemia.

[0019] (5) It helps maintain healthy blood lipid levels.

[0020] Preferably, the product is a pharmaceutical composition or a food, and the food includes health food.

[0021] Preferably, the dosage form of the product is any one of tablets, granules, capsules, oral liquids, and injections; The present invention has at least the following beneficial effects: This invention provides a composition and its application in inhibiting HMG-CoA reductase activity and lowering blood lipids. The composition includes stevia polyphenols and larch resinol in a certain ratio. Their combined use has a synergistic effect and shows outstanding effects in inhibiting HMG-CoA reductase activity, lowering total cholesterol and low-density lipoprotein cholesterol, and raising high-density lipoprotein cholesterol. It is significantly better than the use of each component alone and has important prospects in lowering cholesterol and blood lipids. Detailed Implementation

[0022] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0023] The stevia polyphenols (polyphenol content ≥40%) used in the following examples were purchased from Hebei Qiaorui Biotechnology Co., Ltd., and the larch resinols (content ≥98%) were purchased from Shanghai Maclean Biochemical Technology Co., Ltd.

[0024] Example 1 This embodiment provides a composition consisting of stevia polyphenols and larch resinol in a mass ratio of 1300:1.

[0025] Example 2 This embodiment provides a composition consisting of stevia polyphenols and larch resinol in a mass ratio of 1400:1.

[0026] Example 3 This embodiment provides a composition consisting of stevia polyphenols and larch resinol in a mass ratio of 1350:1.

[0027] Example 4 This embodiment provides a composition consisting of stevia polyphenols and larch resinol in a mass ratio of 1320:1.

[0028] Comparative Example 1 The composition of this comparative example consists only of stevia polyphenols.

[0029] Comparative Example 2 The composition of this comparative example consists of only larchiteol.

[0030] Comparative Example 3 This comparative example provides a composition consisting of stevia polyphenols and larch resinol in a mass ratio of 1250:1.

[0031] Comparative Example 4 This comparative example provides a composition, which consists of stevia polyphenol and lariciresinol in a mass ratio of 1450:1.

[0032] Comparative Example 5 This comparative example provides a composition, which consists of stevia polyphenol and matairesinol in a mass ratio of 1320:1.

[0033] Comparative Example 6 This comparative example provides a composition, which consists of grape polyphenol and lariciresinol in a mass ratio of 1320:1.

[0034] Test Example Animal tests are performed on the compositions of the foregoing examples and comparative examples to test their efficacy in improving hyperlipidemia. The specific methods and results are described below.

[0035] 1. Test consumables (1) Materials Test samples: the compositions of Examples 1-4 and Comparative Examples 1-6, which are stored sealed at 4℃ in dark; Experimental animals: SPF-grade male SD rats (180-220g); Source: Beijing Sibeifu Biotechnology Co., Ltd. [Production License No.: SCXK (Jing) 2024-0001]; High-fat feed (49.3% maintenance feed, 20.0% sucrose, 15.0% lard, 12.5% casein, 1.3% calcium hydrogen phosphate, 1.2% cholesterol, 0.2% sodium cholate, 0.5% stone powder) and maintenance feed are both purchased from Keao Xieli (Tianjin) Feed Co., Ltd.; bedding is purchased from Beijing Sibeifu Biotechnology Co., Ltd..

[0036] (2) Reagents Triglyceride reagent (Cat. No.: 141724023), cholesterol reagent (Cat. No.: 141625007), high-density lipoprotein cholesterol reagent (Cat. No.: 142124028), low-density lipoprotein cholesterol reagent (Cat. No.: 142025006), HMG-CoA reductase assay kit (Cat. No.: H236), etc.

[0037] (3) Instruments YH-M20001 electronic balance, AUW220 electronic balance, centrifuge, microplate reader, automatic biochemical analyzer, gavage needle, dissection instruments, etc.

[0038] 2. Experimental method (1) Animal grouping and administration After the acclimatization period, SD rats were randomly divided into two groups based on body weight: a control group of 10 rats fed a maintenance diet and a model group of 110 rats fed a high-fat diet. Food intake and body weight were recorded weekly. Two weeks after the model group was fed the high-fat diet, blood was collected from the inner canthus of both the control and model groups without fasting. Serum was separated as soon as possible after blood collection, and serum levels of TC, TG, LDL-C, and HDL-C were measured. Based on TC levels, the model group was randomly divided into 11 groups (i.e., model control group, Examples 1-4, and Comparative Examples 1-6), with 10 rats in each group. There were no significant differences in TC, TG, LDL-C, and HDL-C among the different groups after grouping. After grouping, each group was orally administered the corresponding test sample daily. The dosage for Examples 1-4 and Comparative Examples 1-6 was 167 mg / kg BW (all in deionized water), with a gavage volume of 10 mL / kg. The blank control group and model control group were simultaneously given the same volume of the corresponding solvent. The blank control group continued to receive a maintenance diet, while the model control group and other groups continued to receive a high-fat diet. Body weight was measured regularly, and the administration continued for 4 weeks. After the experiment, blood was collected from the abdominal aorta of rats, serum was separated, and four lipid parameters were detected using a fully automated biochemical analyzer. Rats were sacrificed, liver tissue was dissected, and HMG-CoA activity was detected according to the kit instructions.

[0039] (2) Indicator detection Enzyme activity index: HMG-CoA activity; Serum indicators: 4 lipid profiles; 3. Results Statistics and Analysis All data are expressed as mean ± standard deviation and statistical analysis was performed by a professional institution using SPSS 21.0 software. If the variances of the measurement data are homogeneous, or if the variances are homogeneous after transformation, one-way ANOVA was used. If the variances are still heterogeneous after transformation, the rank-sum test was used for statistical analysis.

[0040] 4. Test Results Table 1. Effects of Examples and Comparative Examples on HMG-CoA Activity in Liver Tissue

[0041] Note: Different letters indicate significant differences between groups (P < 0.05).

[0042] The data in Table 1 shows that: ① Compared with the blank control group, the HMG-CoA activity of rats in the model control group was significantly increased (P<0.05), indicating that the model was successfully established.

[0043] ② Compared with the model group, the HMG-CoA activity of rats in Comparative Groups 1-6 all decreased to some extent, but none of them were significant (P>0.05). This indicates that the inhibitory effect of stevia polyphenols or larch resinol alone, the simple combination of the two in a ratio that deviates from the scope of this invention, and the replacement of any of the active components with grape polyphenols or pirarucinol on HMG-CoA activity were all weak and could not produce a statistically significant inhibitory effect.

[0044] ③ Compared with the model group, the HMG-CoA activity of rats in Examples 1-4 was significantly reduced (P<0.05), indicating that when stevia polyphenols and larch resinol are combined within a specific ratio range, they can produce a synergistic effect, achieving significant inhibition of HMG-CoA activity. Among them, the HMG-CoA activity of Example 4 was the lowest and significantly better than all other examples and comparative examples (P<0.05), indicating that this ratio is the optimal embodiment of the present invention.

[0045] ④ The results of the substitution experiment showed that, compared with Example 4, the HMG-CoA activity inhibition effect was significantly reduced in Comparative Examples 5 and 6 after replacing larch resinol with podophyllin and stevia polyphenol with grape polyphenol, respectively, indicating that the above substitution could not achieve the technical effect of the present invention.

[0046] Table 2 Effects of the Examples and Comparative Examples on Four Blood Lipid Parameters in Rats

[0047] Note: Different letters indicate significant differences between groups (P < 0.05).

[0048] From Table 2, we know that: ① Compared with the blank control group, the levels of TC, LDL-C and TG in the model control group rats were significantly increased (P<0.05), and the level of HDL-C was significantly decreased (P<0.05), indicating that the hyperlipidemia model was successfully established and lipid metabolism was disordered.

[0049] ② Compared with the model control group, the levels of TC, LDL-C, and TG in comparative groups 1-6 decreased to some extent, while the level of HDL-C increased to some extent, but there were no significant differences (P>0.05). This indicates that stevia polyphenols or larch resinol administered alone, in simple combinations of the two at ratios deviating from the scope of this invention, and by replacing any of the active components with grape polyphenols or pirarucinol, all had weak effects on improving blood lipid indicators and could not produce statistically significant regulatory effects.

[0050] ③ Compared with the model control group and each comparative example, the levels of TC, LDL-C, and TG in Examples 1-4 were significantly reduced, while the level of HDL-C was significantly increased (P < 0.05). This indicates that when stevia polyphenols and larch resinol are combined within a specific ratio range, they can produce a synergistic effect and comprehensively improve blood lipid levels. Among them, the levels of TC, LDL-C, and TG in Example 4 were the lowest, and the level of HDL-C was the highest, which was significantly better than all other examples and comparative examples (P < 0.05), indicating that this ratio is the optimal implementation scheme of the present invention.

[0051] ④ The substitution experiment results showed that the TC, LDL-C, and TG levels in Comparative Example 5 (where larchoresinol was replaced with podophyllin) and Comparative Example 6 (where stevia polyphenols were replaced with grape polyphenols) were significantly higher than those in Example 4, while the HDL-C level was significantly lower than that in Example 4 (P < 0.05). This indicates that replacing any active component in the specific combination of the present invention with other structural analogs significantly reduces its ability to regulate blood lipids, failing to achieve the technical effects of the present invention. This further proves the irreplaceable nature of the specific combination of stevia polyphenols and larchoresinol in improving dyslipidemia.

[0052] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A composition, characterized in that, The composition comprises stevia polyphenols and larch resinol in a mass ratio of 1300-1400:

1.

2. The composition according to claim 1, characterized in that, The composition has a stevia polyphenol to larch resin alcohol mass ratio of 1300-1350:

1.

3. Use of the composition according to claim 1 or 2 in the preparation of products for the prevention and / or treatment of hyperlipidemia.

4. The application according to claim 3, characterized in that, The product is used for at least one of the following: lowering total cholesterol, lowering LDL cholesterol, and raising HDL cholesterol.

5. Use of the composition of claim 1 or 2 in the preparation of products that help maintain healthy blood lipid levels.

6. The application according to claim 5, characterized in that, The product is used for at least one of the following: lowering total cholesterol, lowering LDL cholesterol, and raising HDL cholesterol.

7. Use of the composition according to claim 1 or 2 in the preparation of a product that inhibits HMG-CoA reductase activity.

8. A product characterized in that, The product comprises the composition according to claim 1 or 2; Preferably, the product has at least one of the following effects: (1) Inhibits HMG-CoA reductase activity; (2) Lower total cholesterol and / or LDL cholesterol levels; (3) Increases high-density lipoprotein cholesterol levels; (4) Prevention and / or treatment of hyperlipidemia; (5) It helps maintain healthy blood lipid levels.

9. The product according to claim 8, characterized in that, The product is a pharmaceutical composition or a food product.

10. The product according to claim 9, characterized in that, The dosage form of the product is any one of tablets, granules, capsules, oral liquids, or injections.

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