A natural anti-sugar composition and its use

Abstract

This invention belongs to the field of biomedical technology and relates to a naturally derived anti-glycation composition and its uses. The anti-glycation composition of this invention contains methoxycapsaicin and / or isopyramidal lactone, and further contains one or more of the following active ingredients: Gastrodia elata powder, Eucommia ulmoides leaf extract, or 4',7-dihydroflavonoids. This invention also provides the use of the anti-glycation composition in the preparation of anti-aging products. All components in the anti-glycation composition of this invention are of natural plant origin, exhibiting higher safety and low or even non-toxicity to humans compared to chemically synthesized substances. This invention provides various compositions containing multiple components, and compared to single-component compositions, these compositions exhibit more efficient AGE inhibition effects. The compositions provided by this invention can be used to prepare anti-aging functional products, thus possessing good market application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine and relates to an anti-sugar composition of natural origin and use thereof. Background Art

[0002] Reducing sugars react non-enzymatically with amino groups of proteins or lipids to form Schiff bases, which are rearranged to produce stable Amadori products, and finally form irreversible advanced glycation end products (AGE) through a series of complex processes. The AGEs formed can bind to proteins, causing changes in their structure and function. When they bind to AGE receptors on the cell surface, they can induce the release of inflammatory factors. AGE accumulation can lead to increased production of reactive oxygen species and induce cell apoptosis. AGE also affects the progression of the disease: AGE can bind to vascular wall proteins, promote vascular hardening, and increase the risk of atherosclerosis; induce the occurrence of diabetic complications, such as diabetic retinopathy and diabetic nephropathy; AGE accumulation in the brain can damage the function of nerve cells and induce the occurrence of neurodegenerative diseases such as Alzheimer's disease.

[0003] The effects of AGE on the skin mainly include: (1) Promoting skin aging: AGE cross-links with collagen and elastin in the skin, causing changes in protein structure, loss of elasticity and flexibility, and resulting in sagging skin and increased wrinkles. (2) Reducing skin elasticity: AGE accumulation will cause skin elasticity to decrease, lose its firmness and smoothness, and become more fragile and easily damaged. (3) Skin color changes: AGE deposition on the skin surface will make the skin dull, yellow, and lose its luster. In addition, AGE will induce pigmentation, causing uneven skin color and chloasma. (4) Accelerating skin inflammation and damage: AGE activates the oxidative stress pathway to produce a large number of free radicals by binding to AGEs receptors on the cell surface, further promoting skin aging, and increasing inflammatory factors by activating inflammatory signals, leading to inflammatory reactions such as skin redness, swelling, and sensitivity.

[0004] AGE prevention and treatment strategies mainly include the following aspects: (1) Control blood sugar levels: Keep blood sugar levels within the normal range through diet control and exercise to reduce the production of AGE. (2) Use antioxidants: Intake of vitamin C, vitamin E and polyphenols can reduce oxidative stress and thus inhibit the formation of AGE. (3) Lifestyle adjustment: Reduce high-sugar and high-fat diets, avoid high-temperature cooking, reduce dietary AGE intake; maintain adequate sleep, reduce smoking, etc. to reduce the formation of AGE. (4) Drug intervention: Research on AGE inhibitors or AGE receptor antagonists can effectively reduce the generation and action of AGE.

[0005] However, the currently known AGE inhibitors have limited anti-sugar effects. The development of new AGE inhibitors will help prevent and treat chronic diseases, delay skin aging, and improve overall health, which has broad and far-reaching significance. Summary of the invention

[0006] In order to overcome the deficiencies of the prior art and enrich the prior art, the present invention provides a composition of one or more natural active ingredients with high AGE inhibitory effects, thereby reducing AGE accumulation, inhibiting AGE damage to the skin, and improving overall health.

[0007] In order to achieve the above-mentioned purpose, the present invention constructs an in vitro glycation model using a BSA-MGO reaction system, and evaluates the inhibitory effect of the combination on AGE formation by adding single substances such as Gastrodia elata powder, Eucommia ulmoides leaf extract, methoxycapsaicin, 4',7-dihydroflavonoids, and isoprenate lactone, or a combination of multiple substances thereof, and proves that the AGE inhibitory effect of the combination is higher than that of each single substance.

[0008] Specifically, the present invention is realized through the following technical solutions:

[0009] In the first aspect, the present invention provides an anti-sugar composition of natural origin, which comprises methoxycapsaicin and / or peucedanum lactone, and further comprises one or more of the following active ingredients: Gastrodia elata powder, Eucommia ulmoides leaf extract or 4',7-dihydroflavone.

[0010] As an optional mode, in the above anti-sugar composition, the anti-sugar composition comprises the following four or five active ingredients: Gastrodia elata powder, Eucommia ulmoides leaf extract, methoxycapsaicin, 4',7-dihydroflavone or peucedanum lactone.

[0011] Preferably, the anti-sugar composition is made of Gastrodia elata powder, Eucommia ulmoides leaf extract, methoxycapsaicin and 4',7-dihydroflavone.

[0012] Preferably, the anti-sugar composition is made of Gastrodia elata powder, Eucommia ulmoides leaf extract, methoxycapsaicin and peucedanum odoratum lactone.

[0013] Preferably, the anti-sugar composition is made of Gastrodia elata powder, Eucommia ulmoides leaf extract, 4',7-dihydroflavone and peucedanum lactone.

[0014] Preferably, the anti-sugar composition is made of Gastrodia elata powder, methoxycapsaicin, 4',7-dihydroflavone and peucedanum lactone.

[0015] Preferably, the anti-sugar composition is made of eucommia leaf extract, methoxycapsaicin, 4',7-dihydroflavonoids, and peucedanum lactone.

[0016] More preferably, the anti-sugar composition is made of Gastrodia elata powder, Eucommia ulmoides leaf extract, methoxycapsaicin, 4',7-dihydroflavone, and peucedanum lactone.

[0017] As an optional manner, in the above-mentioned anti-sugar composition, the concentration range of Gastrodia elata powder is 0.5 mg / mL-10 mg / mL, the concentration range of Eucommia ulmoides leaf extract is 0.5 mg / mL-10 mg / mL, the concentration range of methoxycapsaicin is 0.4 μg / mL-50 μg / mL, the concentration range of 4',7-dihydroflavone is 0.04 μg / mL-2 μg / mL, and the concentration range of peucedanum lactone is 0.08 μg / mL-10 μg / mL.

[0018] As an optional method, in the above anti-sugar composition, the concentration of Gastrodia elata powder is 0.5 mg / mL, the concentration of Eucommia ulmoides leaf extract is 0.5 mg / mL, the concentration of methoxycapsaicin is 0.4 μg / mL, the concentration of 4',7-dihydroflavone is 0.04 μg / mL, and the concentration of peucedanum lactone is 0.08 μg / mL.

[0019] As an optional manner, in the above anti-sugar composition, the anti-sugar composition can effectively inhibit the formation of advanced glycation end products (AGE).

[0020] As an optional mode, in the above anti-sugar composition, the composition has a higher AGE inhibition efficiency than a single component.

[0021] In a second aspect, the present invention provides use of the anti-sugar composition described in the first aspect in the preparation of anti-aging products.

[0022] As an optional mode, in the above-mentioned use, the anti-aging includes alleviating or preventing skin aging, cell aging or photoaging.

[0023] As an option, in the above use, the product is an oral product or an external product.

[0024] As an option, in the above use, the product is a cosmetic or a medicine.

[0025] As an optional mode, in the above-mentioned use, the product is an oral solution, liquid suspension, injection, tablet, pill, granule, powder, film, capsule, spray, aerosol, facial mask, facial cream, essence, lotion, toner or makeup.

[0026] As an optional mode, in the above-mentioned use, the product further comprises auxiliary materials or excipients commonly used in cosmetics or medicines, and the amount of the composition in the product is 0.5%-20% by weight.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] (1) The components in the anti-sugar composition of the present invention are all derived from natural plants. Compared with chemically synthesized substances, they are safer and have low or even no toxicity to the human body.

[0029] (2) The present invention provides a variety of compositions containing multiple components, and compared with a single component, the composition has a more efficient AGE inhibition effect.

[0030] (3) The composition provided by the present invention can be used to prepare anti-aging functional products and therefore has good market application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 : AGE inhibition rate of the tested substance at different concentrations.

[0032] Figure 2 : Inhibitory effects of single drugs and combinations on AGE formation in vitro. DETAILED DESCRIPTION

[0033] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0034] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0035] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0036] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present application description and examples are exemplary only.

[0037] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0038] The present invention will be further described with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the scope of the present invention.

[0039] If no specific techniques or conditions are specified in the examples, the techniques or conditions described in the literature in the field or the product instructions are used. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0040] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0041] Example: Example 1

[0042] The inhibitory effects of Gastrodia elata powder, Eucommia ulmoides leaf extract, methoxycapsaicin, 4',7-dihydroflavonoids, and isoprenate lactone on AGE formation in the BSA-MGO model.

[0043] 1. Experimental Materials

[0044] 1.1 Experimental reagents

[0045] Methylglyoxal (MGO) and bovine serum albumin (BSA).

[0046] 1.2 Experimental samples

[0047] Gastrodia elata powder, Guangdong Qingyunshan Pharmaceutical Co., Ltd., code: C040202-02. Eucommia ulmoides leaf extract, Guangdong Qingyunshan Pharmaceutical Co., Ltd., code: C072404-01. Yangonin, CAS No. 500-62-9. 4',7-Dihydroxyflavone, CAS No. 2196-14-7. Marmesin, CAS No. 495-30-7. Aminoguanidine (positive control), CAS No. 1937-19-5.

[0048] 1.3 Experimental instruments

[0049] Microplate reader (Synergy H1), Bio-Tek, USA.

[0050] 2. Experimental Methods

[0051] 2.1 Construction of in vitro AGE generation system

[0052] BSA and MGO were prepared into 10 mg / mL and 25 mM reaction solutions, respectively, and the solvent was phosphate buffer (10 mM, pH 7.4) to form a BSA-MGO reaction system as a model group for AGE generation. The microplate reader was set to detect the wavelength at 370 nm and the reference wavelength at 440 nm, and the OD values ​​on the 0th and 3rd days were measured, and the AGE generation was detected based on the OD values.

[0053] 2.2 Determination of inhibition of AGE formation in vitro

[0054] Mixed incubation solutions containing Gastrodia elata powder (0.5 mg / mL, 1 mg / mL, 5 mg / mL, 10 mg / mL), Eucommia ulmoides leaf extract (0.5 mg / mL, 1 mg / mL, 5 mg / mL, 10 mg / mL), methoxy-peppermint (0.4 μg / mL, 2 μg / mL, 10 μg / mL, 50 μg / mL), 4',7-dihydroflavonoids (0.04 μg / mL, 0.08 μg / mL, 0.4 μg / mL, 2 μg / mL) and isoprenate lactone (0.08 μg / mL, 0.4 μg / mL, 2 μg / mL, 10 μg / mL) were prepared with liquid containing 10 mg / mL BSA and 25 mM MGO. The control group was a BSA-MGO reaction system without the test substance. The above liquids were sterilized and filtered with a 0.2 μm filter membrane and dispensed into 1.5 mL conical bottom centrifuge tubes.

[0055] Then, 100 μL of the reaction solution was placed in a black 96-well ELISA plate, and the fluorescence value on day 0 was detected. The OD value of the formed AGE was measured by an ELISA instrument. The remaining reaction solution was placed in a 37°C incubator for 3 days, and 100 μL of the reaction solution was placed in a black 96-well ELISA plate on the 3rd day to detect the fluorescence value on the 3rd day. The OD value of the formed AGE was measured by an ELISA instrument with a detection wavelength of 370 nm and a reference wavelength of 440 nm.

[0056] 2.3 Data processing and statistical analysis methods (each group of experiments was repeated at least 3 times)

[0057] The AGE inhibition rate was calculated using the formula;

[0058] AGE inhibition rate = (CT) / C×100

[0059] Wherein, C is the fluorescence intensity change fold of the control group (blank case), that is, the fluorescence intensity change fold of glycated bovine serum albumin in the BSA-MGO reaction system in the absence of anti-glycation and anti-aging substances; T is the fluorescence intensity change fold of glycated bovine serum albumin in the BSA-MGO reaction system in the presence of anti-glycation and anti-aging substances.

[0060] 3. Experimental Results

[0061] The inhibitory effect of the experimental samples on AGE, such as Figure 1 As shown. Figure 1 Results The AGE inhibition rate was compared and analyzed. It was found that the AGE inhibition rate of aminoguanidine at 1 mM was 9.64%, and the AGE inhibition rate at 10 mM was 51.43%. The AGE inhibition rates of Gastrodia powder at 0.5 mg / mL, 1 mg / mL, 5 mg / mL, and 10 mg / mL were 16.73%, 23.59%, 51.02%, and 63.36%, respectively. The AGE inhibition rates of Eucommia leaf extract at 0.5 mg / mL, 1 mg / mL, 5 mg / mL, and 10 mg / mL were 15.17%, 26.15%, 58.75%, and 66.49%, respectively. The AGE inhibition rates of methoxycapsaicin at 0.4 μg / mL, 2 μg / mL, 10 μg / mL, and 50 μg / mL were 9.61%, 28.51%, 64.29%, and 81.27%, respectively. The AGE inhibition rates of 4',7-dihydroflavone at 0.04 μg / mL, 0.08 μg / mL, 0.4 μg / mL, and 2 μg / mL were 9.56%, 17.54%, 48.86%, and 73.22%, respectively. The AGE inhibition rates of peucedanum argenteae lactone at 0.08 μg / mL, 0.4 μg / mL, 2 μg / mL, and 10 μg / mL were 9.47%, 32.23%, 75.52%, and 83.08%, respectively.

[0062] The above results prove that in the in vitro BSA-MGO system, Gastrodia elata powder, Eucommia ulmoides leaf extract, methoxycapsaicin, 4',7-dihydroflavone, and peucedanum odoratum can significantly inhibit AGE formation, and this inhibitory effect is concentration-dependent.

[0063] Example 2

[0064] AGE inhibitory effects of the six compositions.

[0065] 1. Experimental Materials

[0066] 1.1 Experimental reagents

[0067] Methylglyoxal (MGO) and bovine serum albumin (BSA).

[0068] 1.2 Experimental samples

[0069] Gastrodia elata powder, Guangdong Qingyunshan Pharmaceutical Co., Ltd., code: C040202-02. Eucommia ulmoides leaf extract, Guangdong Qingyunshan Pharmaceutical Co., Ltd., code: C072404-01. Yangonin, CAS No. 500-62-9. 4',7-Dihydroxyflavone, CAS No. 2196-14-7. Marmesin, CAS No. 495-30-7. Aminoguanidine (positive control), CAS No. 1937-19-5.

[0070] 1.3 Experimental instruments

[0071] Microplate reader (Synergy H1), Bio-Tek, USA.

[0072] 2. Experimental Methods

[0073] 2.1 Determination of the inhibition rate of single drugs and combination drugs on the generation of AGE in vitro

[0074] The mixed incubation solutions containing 0.5 mg / mL Gastrodia elata powder, 0.5 mg / mL Eucommia ulmoides leaf extract, 0.4 μg / mL methoxy-peppermint, 0.04 μg / mL 4',7-dihydroflavonoids, 0.08 μg / mL isoprene lactone and the compositions in Table 1 were prepared with liquids containing 10 mg / mL BSA and 25 mM MGO. The control group was a BSA-MGO reaction system without the test substance. The above liquids were sterilized and filtered with a 0.2 μm filter membrane and dispensed into 1.5 mL conical bottom centrifuge tubes.

[0075] Table 1: Composition of ingredients

[0076]

[0077] Then, 100 μL of the reaction solution was placed in a black 96-well ELISA plate, and the fluorescence value on day 0 was detected. The OD value of the formed AGE was measured by an ELISA instrument. The remaining reaction solution was kept away from light and placed in a 37°C incubator for 3 days, and 100 μL of the reaction solution was placed in a black 96-well ELISA plate on the 3rd day to detect the fluorescence value on the 3rd day. The OD value of the formed AGE was measured by an ELISA instrument with a detection wavelength of 370 nm and a reference wavelength of 440 nm.

[0078] 2.2 Data processing and statistical analysis methods (each group of experiments was repeated at least 3 times)

[0079] The AGE inhibition rate was calculated using the formula;

[0080] AGE inhibition rate = (CT) / C×100

[0081] Wherein, C is the fluorescence intensity change fold of the control group (blank case), that is, the fluorescence intensity change fold of glycated bovine serum albumin in the BSA-MGO reaction system in the absence of anti-glycation and anti-aging substances; T is the fluorescence intensity change fold of glycated bovine serum albumin in the BSA-MGO reaction system in the presence of anti-glycation and anti-aging substances.

[0082] 3. Experimental Results

[0083] The inhibitory effects of single substances and combinations on AGE are as follows Figure 2 As shown, the AGE inhibition rate of 0.5 mg / mL Gastrodia elata powder was 14.60%, the AGE inhibition rate of 0.5 mg / mL Eucommia ulmoides leaf extract was 10.61%, the AGE inhibition rate of 0.4 μg / mL methoxycapsaicin was 10.14%, the AGE inhibition rate of 0.04 μg / mL 4'7-dihydroflavone was 13.90%, the AGE inhibition rate of 0.08 μg / mL peucedanum lactone was 8.36%, and the AGE inhibition rates of combinations 1-6 were 24.35%, 25.98%, 24.29%, 26.72%, 27.96%, and 30.15%, respectively.

[0084] The above results indicate that the AGE inhibition effects of the six compositions comprising multiple components are significantly better than those of each single substance.

[0085] The above embodiments are only used as explanations of the present invention, and are not intended to limit the embodiments of the present invention. Researchers in the field may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. Use of peucedanum arvense lactone in the preparation of an anti-sugar composition, characterized in that: The isopruciformis lactone effectively inhibits the formation of advanced glycation end products (AGE), and the concentration range of the isopruciformis lactone in the anti-sugar composition is 0.08 μg / mL-10 μg / mL.

2. The use according to claim 1, characterized in that: The anti-sugar composition is prepared from gastrodia elata powder, eucommia leaf extract, methoxycapsaicin, 4',7-dihydroxyflavone, and peucedanum odoratum lactone. In the anti-sugar composition, the concentration of gastrodia elata powder is 0.5 mg / mL, the concentration of eucommia leaf extract is 0.5 mg / mL, the concentration of methoxycapsaicin is 0.4 μg / mL, the concentration of 4',7-dihydroxyflavone is 0.04 μg / mL, and the concentration of peucedanum odoratum lactone is 0.08 μg / mL.

3. Use of the anti-sugar composition in the preparation of anti-aging products, characterized in that: The anti-sugar composition is prepared from gastrodia elata powder, eucommia leaf extract, methoxycapsaicin, 4',7-dihydroxyflavone, and peucedanum odoratum lactone. In the anti-sugar composition, the concentration of gastrodia elata powder is 0.5 mg / mL, the concentration of eucommia leaf extract is 0.5 mg / mL, the concentration of methoxycapsaicin is 0.4 μg / mL, the concentration of 4',7-dihydroxyflavone is 0.04 μg / mL, and the concentration of peucedanum odoratum lactone is 0.08 μg / mL.

4. The use according to claim 3, characterized in that: The anti-aging includes alleviating or preventing skin aging, cell aging or photoaging.

5. The use according to claim 3, characterized in that: The product is an oral product or an external product.

6. The use according to claim 3, characterized in that: The product is a cosmetic or a medicine.

7. The use according to claim 5, characterized in that: The product is an oral solution, a liquid suspension, an injection, a tablet, a pill, a granule, a powder, a film, a capsule, a spray, an aerosol, a facial mask, a facial cream, an essence, a lotion, a toner or a makeup.

8. The use according to claim 3, characterized in that: The product also contains auxiliary materials commonly used in cosmetics or medicines. The amount of the composition in the product is 0.5%-20% by weight.

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