Dioscorea zingiberensis / pericarpium citri reticulatae / hawthorn extract compound, preparation thereof and application of compound in preparation of hypoglycemic products

Through the complexation of ginger extract with tangerine peel and hawthorn extract, the hypoglycemia effect was evaluated by using the equiline diagram method and the Chou-Talalay combined index method, which solved the problem of lack of systematic research on hypoglycemia in the existing technology, and achieved significant hypoglycemia effect and synergistic effect.

CN120189482APending Publication Date: 2025-06-24SOUTH CHINA AGRICULTURAL UNIVERSITY
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Patent Information

Application Number
CN202510327829.0
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-03-19
Publication Date
2025-06-24

AI Technical Summary

Technical Problem

In the prior art, there has been no systematic research on the synergistic or antagonistic effect of the combination of ginger, tangerine peel and hawthorn in lowering blood sugar, and there is a lack of effective application of lowering blood sugar products.

Method used

The extract of ginger ginger was used as the main material, and the extract of tangerine peel and hawthorn were screened as complexes. The synergistic effect of hypoglycemia was evaluated in vitro by using the equivalent line diagram method and the index method of Chou-Talalay in vitro, and its hypoglycemia activity and synergistic effect were further studied through the IR-HepG2 cell model and the nematode high sugar model.

Benefits of technology

The IC50 of ginger, tangerine peel and hawthorn extracts inhibited α-glucosidase activity was 0.438 mg/mL, 0.122 mg/mL, and 0.156 mg/mL, respectively. The complex showed synergistic effects, significantly improving glucose consumption and glycogen synthesis in IR-HepG2 cells, alleviating oxidative stress in the high-sugar model of nematodes, and reducing glucose and lipid accumulation.

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Abstract

The invention discloses a small yellow ginger / pericarpium citri reticulatae / hawthorn extract compound, preparation thereof and application of the compound in preparation of a hypoglycemic product. According to the invention, analysis evaluation and blood sugar reduction research are carried out on alpha-glucosidase inhibition capability and joint indexes of independent and compounded small yellow ginger, dried orange peel and hawthorn extracts. A result shows that the small yellow ginger-dried orange peel compound (1: 2), the small yellow ginger-hawthorn compound (1: 2) and the small yellow ginger-hawthorn compound (1: 3) have a synergistic blood sugar reducing effect; in vitro, the small yellow ginger extract and the compound thereof can increase glucose consumption and glycogen synthesis of IR-HepG2 cells; in vivo, the yellow ginger extract and the compound thereof can significantly relieve oxidative stress of nematodes caused by hyperglycemia, promote glucose utilization of peripheral tissues and effectively inhibit abnormal lipid accumulation. The hypoglycemic effect of the compound is obviously superior to that of a single small yellow ginger extract. The invention provides a theoretical reference for developing a composite hypoglycemic product.
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Description

Technical Field

[0001] The present invention relates to the technical field of plant extracts, and particularly to a compound of extracts of Zingiber officinale Rosc. var. flavum Hand.-Mazz., dried tangerine peel and hawthorn, its preparation and application in the preparation of hypoglycemic products. Background Art

[0002] Zingiber officinale Rosc. var. flavum Hand.-Mazz. is a variety of ginger and an important medicinal and edible herbaceous plant, which is widely cultivated in tropical, subtropical and some temperate regions of the world, including parts of Asia, Africa, the Americas and Europe. Zingiber officinale Rosc. var. flavum Hand.-Mazz. has important applications in traditional medicine and the food industry. Zingiber officinale Rosc. var. flavum Hand.-Mazz. contains rich bioactive components, such as polyphenols, flavonoids, proteins, alkaloids and polysaccharides. Research shows that these components have a variety of pharmacological activities, including lipid-lowering, anti-diabetic, antioxidant and anti-tumor effects.

[0003] Dried tangerine peel is the dried mature pericarp of Citrus reticulata Blanco and its cultivated varieties of the Rutaceae family, and is a natural resource with medicinal, edible and tea-making values. Research shows that dried tangerine peel is rich in various active components such as volatile oils, flavonoids, polysaccharides and alkaloids, and has significant biological activities such as antioxidant, anti-inflammatory, antibacterial, lipid-lowering and hypoglycemic effects.

[0004] Hawthorn (Crataegus pinnatifida Bge.) is a plant of the genus Crataegus in the subfamily Maloideae of the Rosaceae family, and is a fruit with both medicinal and edible values. Research shows that hawthorn is rich in chemical components such as polyphenols, polysaccharides, flavonoids and triterpenoids, and has various biological activities such as hypoglycemic, lipid-lowering, antioxidant, anti-inflammatory and anti-cancer effects.

[0005] The combined application of Chinese herbal medicines is commonly and widely used in functional foods in the form of formula compatibility. Research shows that the active effects of multiple Chinese herbal medicines used in combination are often superior to those of single active ingredients, and their advantages are mainly reflected in the characteristics of multi-target and multi-mechanism actions. The combined compounding can not only enhance the functional activity, reduce the dosage, but also delay the development of drug resistance, reduce toxicity, and save resources and costs. Wagner et al. pointed out that the compounding of Chinese herbal medicines significantly improved the bioavailability and therapeutic effect through synergistic effects, while reducing adverse reactions. With the in-depth study of the bioactive components of ginger, its combined application with other substances has gradually become one of the research hotspots. Shalaby et al. found that ginger could significantly enhance the hepatoprotective effect of atorvastatin by studying the combined application of ginger and atorvastatin. The research results showed that the active ingredients in ginger alleviated the liver injury caused by atorvastatin and improved liver function through antioxidant and anti-inflammatory mechanisms. Li et al. explored the combined application of dietary jujube polysaccharide and 6-gingerol in ginger and found that they had a synergistic effect in antioxidant and anti-tumor activities. Research shows that the combined application of 6-gingerol and jujube polysaccharide can significantly enhance the free radical scavenging ability and inhibit the proliferation of tumor cells. Summary of the Invention

[0006] The object of the present invention is to overcome the disadvantages and deficiencies of the prior art and provide the application of small yellow ginger extract or its compound in the preparation of hypoglycemic products.

[0007] Another object of the present invention is to provide a preparation method of a compound of small yellow ginger extract.

[0008] Another object of the present invention is to provide a compound of small yellow ginger extract.

[0009] At present, there is no systematic research report on the synergistic or antagonistic effects of the compound combinations of small yellow ginger with tangerine peel and small yellow ginger with hawthorn in terms of hypoglycemia. Therefore, the research on the hypoglycemic activity of the compound of small yellow ginger with tangerine peel and small yellow ginger with hawthorn respectively has important theoretical value and potential application prospects.

[0010] The present invention uses small yellow ginger extract as the main material, screens out tangerine peel and hawthorn extracts as the compound through in vitro hypoglycemic activity tests, and evaluates the in vitro synergistic hypoglycemic effects of the compound of small yellow ginger extract with tangerine peel and hawthorn extracts respectively by using the isobologram method and the Chou-Talalay combination index method. In addition, the hypoglycemic activity and synergistic effect of small yellow ginger extract and its compound are further studied through the IR-HepG2 cell model and the nematode hyperglycemic model, providing new scientific evidence for the potential of ginger in the fields of functional foods and the combined application of active ingredients.

[0011] The object of the present invention is achieved by the following technical solutions:

[0012] Use of the small yellow ginger extract or its compound in the preparation of a hypoglycemic product, wherein the compound is a compound of the small yellow ginger extract and the tangerine peel extract, or a compound of the small yellow ginger extract and the hawthorn extract.

[0013] Further, the hypoglycemic product is a food with the function of helping to maintain a healthy blood glucose level, a health product with the function of helping to maintain a healthy blood glucose level, or a hypoglycemic drug.

[0014] Further, in the compound of the small yellow ginger extract and the tangerine peel extract, the ratio of the small yellow ginger extract to the tangerine peel extract is 1:1.5 to 2.5; preferably 1:2.

[0015] Further, in the compound of the small yellow ginger extract and the hawthorn extract, the ratio of the small yellow ginger extract to the hawthorn extract is 1:1.5 to 3.5; preferably 1:2 or 1:3.

[0016] Further, when the hypoglycemic product is a hypoglycemic drug, the hypoglycemic product also contains other pharmaceutically acceptable carriers or excipients and is made into a pharmaceutically acceptable dosage form.

[0017] Further, the small yellow ginger extract is prepared by the following steps: weighing small yellow ginger powder, adding an ethanol solution, performing ultrasonic treatment, filtering by suction, centrifuging the filtrate, concentrating the supernatant, freeze-drying, and storing in a refrigerator for later use.

[0018] Further, the ethanol solution is a 50wt% - 90wt% ethanol solution; preferably a 71wt% ethanol solution.

[0019] Further, the ratio of the small yellow ginger powder to the ethanol solution is 1g:15 - 20mL; preferably 1g:19mL.

[0020] Further, the conditions for the ultrasonic treatment are 45 - 55°C, 80 - 120W, 30 - 35min; preferably 50°C, 100W, 32min.

[0021] Further, the conditions for the centrifugation are 3000 - 5000rpm, 5 - 15min; preferably 4000rpm, 10min.

[0022] Further, the concentration is carried out at 45 - 55°C; preferably rotary evaporation concentration under vacuum at 50°C.

[0023] Further, the tangerine peel extract and the hawthorn extract are prepared by the following steps: weighing tangerine peel or hawthorn powder, mixing with water, performing hot water extraction, filtering by suction, centrifuging to collect the supernatant, extracting the residue again according to the above method, performing vacuum concentration, and freeze-drying to obtain the tangerine peel or hawthorn extract.

[0024] Further, the ratio of the tangerine peel extract or hawthorn extract to water is 1 g: 5-20 mL; preferably 1 g: 10 mL.

[0025] Further, the conditions for hot water extraction are 85-95 °C and 1-3 h; preferably 90 °C and 2 h.

[0026] Further, the conditions for centrifugation are 3000-5000 rpm and 5-15 min; preferably 4500 rpm and 10 min.

[0027] Further, the vacuum concentration is carried out under vacuum at 55-65 °C; preferably under vacuum at 60 °C.

[0028] A hypoglycemic composition is composed of the following components in parts by mass: 1 part of zingiber officinale extract, 1.5-2.5 parts of tangerine peel extract, or 1 part of zingiber officinale extract, 1.5-3.5 parts of hawthorn extract.

[0029] Further, it is composed of the following components in parts by mass: 1 part of zingiber officinale extract, 2 parts of tangerine peel extract, or 1 part of zingiber officinale extract, 3 parts of hawthorn extract.

[0030] The present invention has the following advantages and effects compared with the prior art:

[0031] The present invention uses zingiber officinale extract as the main raw material, and tangerine peel and hawthorn extracts as auxiliary materials, and measures its hypoglycemic activity with the inhibition experiment of α-glucosidase activity as an index; the equivalent line diagram method and the combination index method are used to evaluate the interaction of zingiber officinale extract with tangerine peel and hawthorn extracts in compounding hypoglycemia, and the IR-HepG2 cell model and the nematode hyperglycemic model are used to further study the hypoglycemic effect of the compound with synergistic hypoglycemic effect. The results show that the IC 50 values of zingiber officinale, tangerine peel and hawthorn extracts for inhibiting α-glucosidase activity are 0.438 mg / mL, 0.122 mg / mL and 0.156 mg / mL respectively; according to the measurement results, the zingiber officinale-tangerine peel compound may have a synergistic effect at mass ratios of 1:1, 1:2 and 1:3, and the zingiber officinale-hawthorn compound may have a synergistic effect at mass ratios of 1:2 and 1:3. Through the equivalent line diagram method and the combination index method, the zingiber officinale-tangerine peel compound (1:2), the zingiber officinale-hawthorn compound (1:2) and the zingiber officinale-hawthorn compound (1:3) have a synergistic effect on the inhibition of α-glucosidase activity (IC 50 : 0.122 mg / mL, 0.166 mg / mL and 0.160 mg / mL), and the zingiber officinale-tangerine peel compound (1:1) has an additive effect (IC 50= 0.185 mg / mL), the Zingiber officinale - Citrus reticulata Blanco complex (1:3) has an antagonistic effect (IC 50 = 0.160 mg / mL). In vitro in IR - HepG2 cells, at 400 μg / mL, the treatment groups of Zingiber officinale extract, Zingiber officinale - Citrus reticulata Blanco complex (1:2), Zingiber officinale - Crataegus pinnatifida complex (1:2), and Zingiber officinale - Crataegus pinnatifida complex (1:3) could increase the glucose consumption of IR - HepG2 cells by 16.86%, 18.09%, 22.51%, and 18.97% respectively, and increase the glycogen synthesis by 13.18%, 14.90%, 17.10%, and 15.67% respectively. In vivo, the treatment groups of Zingiber officinale extract, Zingiber officinale - Citrus reticulata Blanco complex (1:2), Zingiber officinale - Crataegus pinnatifida complex (1:2), and Zingiber officinale - Crataegus pinnatifida complex (1:3) could alleviate the oxidative stress caused by hyperglycemia in nematodes. Compared with the model group, at 400 μg / mL, the treatment groups of Zingiber officinale extract, Zingiber officinale - Citrus reticulata Blanco complex (1:2), Zingiber officinale - Crataegus pinnatifida complex (1:2), and Zingiber officinale - Crataegus pinnatifida complex (1:3) significantly increased the GSH content (17.05%, 57.68%, 69.89%, and 64.27%) and SOD activity (21.66%, 32.52%, 46.99%, and 35.07%), while reducing the MDA content (13.87%, 23.04%, 37.43%, and 29.29%). In addition, the treatment groups of Zingiber officinale extract, Zingiber officinale - Citrus reticulata Blanco complex (1:2), Zingiber officinale - Crataegus pinnatifida complex (1:2), and Zingiber officinale - Crataegus pinnatifida complex (1:3) also promoted the glucose consumption in nematodes (36.39%, 54.71%, 66.10%, and 56.21%), inhibited the synthesis of triglycerides (32.12%, 43.76%, 56.43%, and 48.78%), and the accumulation of lipids (30.11%, 42.55%, 47.35%, and 39.02%). Generally speaking, the Zingiber officinale extract and its complexes showed hypoglycemic effects in HepG2 cells and nematode models, accompanied by changes in indicators related to oxidative stress, glucose metabolism, and lipid metabolism. This finding provides a basis for the development of new therapies for treating glucose metabolism disorders such as type 2 diabetes (T2D). In addition, due to the synergistic effect of multiple components in the complex, the hypoglycemic effect of the complex is significantly better than that of the single Zingiber officinale extract. The synergistic effect may be achieved by enhancing biological activity or acting on multiple targets simultaneously, thus improving the overall hypoglycemic effect. Description of the Drawings

[0032] Figure 1 It is a research result diagram of the effects of Zingiber officinale extract (GE), Citrus reticulata Blanco extract (DTPE), and Crataegus pinnatifida extract (CPE) on α - glucosidase activity; Note: Different letters indicate significant differences (p < 0.05).

[0033] Figure 2 Figure showing the results of the study on the effects of different mass ratio compounds on α-glucosidase activity; where A is the extract of dried tangerine peel (DTPE), B is the extract of hawthorn fruit (CPE) (concentration in A is 1 mg / mL; concentration in B is 0.5 mg / mL); Note: Different letters indicate significant differences (p < 0.05).

[0034] Figure 3 Figure showing the results of the study on the effects of the compound of ginger extract (GE) with the extracts of dried tangerine peel and hawthorn fruit (DTPE and CPE) on α-glucosidase activity; where A is the extract of dried tangerine peel and B is the extract of hawthorn fruit; Note: Different letters indicate significant differences (p < 0.05).

[0035] Figure 4 Figure showing the IC 50 isobologram of the inhibition of α-glucosidase activity by the compound of ginger with the extracts of dried tangerine peel and hawthorn fruit (GE, DTPE and CPE) (point A is GE:DTPE = 1:1, point B is GE:DTPE = 1:2, point C is GE:DTPE = 1:3, point D is GE:CPE = 1:2, point E is GE:CPE = 1:3).

[0036] Figure 5 Figure showing the results of the study on the effects of ginger extract and its compounds on the metabolic functions of HepG2 and IR-HepG2 cells; where A is cell viability (HepG2), B is glucose consumption (IR-HepG2), C is glycogen synthesis (IR-HepG2) (treatment groups: ginger extract (GE), ginger-dried tangerine peel compound (1:2) (GE:DTPE = 1:2), ginger-hawthorn compound (1:2) (GE:CPE = 1:2), ginger-hawthorn compound (1:3) (GE:CPE = 1:3)); Note: * indicates significant difference, p < 0.05; ** indicates extremely significant difference, p < 0.001.

[0037] Figure 6 Figure showing the results of the study on the regulation of oxidative stress indices of N2 nematodes by ginger extract and its compounds under high-glucose environment; where A is the content of GSH, B is the content of MDA, C is the activity of SOD (treatment groups: ginger extract (GE), ginger-dried tangerine peel compound (1:2) (GE:DTPE = 1:2), ginger-hawthorn compound (1:2) (GE:CPE = 1:2), ginger-hawthorn compound (1:3) (GE:CPE = 1:3)); Note: * indicates significant difference, p < 0.05; ** indicates extremely significant difference, p < 0.001.

[0038] Figure 7Figure showing the results of the study on the effects of Zingiber officinale extract and its combinations on glucose and fat content in N2 nematodes under high - glucose conditions; where A is the glucose content, B is the triglyceride content, C is the lipid accumulation amount (treatment groups: Zingiber officinale extract (GE), Zingiber officinale - Citrus reticulata Blanco combination (1:2) (GE:DTPE = 1:2), Zingiber officinale - Crataegus pinnatifida combination (1:2) (GE:CPE = 1:2), Zingiber officinale - Crataegus pinnatifida combination (1:3) (GE:CPE = 1:3)); Note: * significant difference, p < 0.05; ** extremely significant difference, p < 0.001.

[0039] Figure 8 Figure of Oil Red O staining results; where A - B are the high - glucose treatment group and the control group, C - E are the Zingiber officinale extract treatment groups (50, 100, 200 μg / mL), F - H are the Zingiber officinale - Citrus reticulata Blanco combination (1:2) treatment groups (50, 100, 200 μg / mL), I - K are the Zingiber officinale - Crataegus pinnatifida combination (1:2) treatment groups (50, 100, 200 μg / mL), L - N are the Zingiber officinale - Crataegus pinnatifida combination (1:3) treatment groups (50, 100, 200 μg / mL). Detailed implementation manners

[0040] The present invention will be further described in detail below in conjunction with the embodiments and the accompanying drawings, but the implementation manners of the present invention are not limited thereto.

[0041] The Zingiber officinale powder in the following embodiments is provided by Lianshan Zhuangyao Yuan Agricultural Development Co., Ltd. (Qingyuan, China); 2,2 - azino - bis(3 - ethylbenzothiazoline - 6 - sulfonic acid) diammonium salt (ABTS), vitamin C, 4 - nitrophenyl - α - D - glucopyranoside (pNPG), bovine serum albumin (BSA), cholesterol, magnesium sulfate, anhydrous magnesium sulfate are purchased from Macklin Biochemical Technology Co., Ltd. (Shanghai, China); 1,1 - diphenyl - 2 - picrylhydrazyl (DPPH), 2,2′ - azobis(2 - methylpropionamidine) dihydrochloride (AAPH), α - glucosidase are purchased from Yuanye Biotechnology Co., Ltd. (Shanghai, China); DMEM medium, fetal bovine serum, phosphate - buffered saline (PBS) and penicillin - streptomycin antibiotic mixture are purchased from Gibco (Shanghai, China); glucosamine is purchased from Beyotime Biotechnology Co., Ltd. (Shanghai, China); glucose assay kit, glycogen content detection kit are from Nanjing Jiancheng Bioengineering Institute (Nanjing, China); tryptone is purchased from Aoboxing Biotechnology Co., Ltd. (Beijing, China); yeast extract powder is purchased from Huankai Microbial Technology Co., Ltd. (Guangdong, China); agar powder is purchased from Saiguo Biotechnology Co., Ltd. (Guangdong, China); all other chemicals and solvents used are of analytical grade and commercially available.

[0042] Example 1

[0043] 1. Preparation of Samples

[0044] Small yellow ginger: The small yellow ginger powder is passed through an 80 - mesh sieve and placed in an oven at 60 °C for drying until the weight is constant.

[0045] Dried tangerine peel: The dried tangerine peel is placed in an oven at 60 °C and dried to a constant weight, then crushed with a pulverizer, passed through an 80 - mesh sieve, and finally stored at 4 °C for later use.

[0046] Hawthorn: Fresh hawthorn is sliced and placed in an oven at 60 °C for drying to a constant weight, crushed with a pulverizer and passed through an 80 - mesh sieve, and then stored at 4 °C for later use.

[0047] 2. Preparation of Extracts

[0048] Small yellow ginger extract: Weigh a certain mass of the small yellow ginger powder sample, add 71% ethanol solution according to a certain solid - to - liquid ratio (1:19, m / v), treat it at 50 °C under an ultrasonic power of 100 W for 32 min, filter by suction, centrifuge the filtrate at 4000 rpm for 10 min, concentrate the supernatant under vacuum at 50 °C through a rotary evaporator, and store it at - 20 °C after freeze - drying for later use.

[0049] Dried tangerine peel and hawthorn extracts: Weigh a certain mass of the sample powder, mix it with primary water according to a solid - to - liquid ratio of 1:10 (g / mL), extract it with hot water at 90 °C for 2 h, filter by suction, centrifuge at 4500 rpm for 10 min, collect the supernatant, and extract the residue again according to the above method. Concentrate it under vacuum at 60 °C and finally obtain dried tangerine peel and hawthorn extracts after freeze - drying respectively.

[0050] 3. Preparation of Extract Solutions

[0051] Take the obtained small yellow ginger, dried tangerine peel, and hawthorn extracts, and prepare gradient - concentration small yellow ginger, dried tangerine peel, and hawthorn extract solutions with primary water.

[0052] 4. Preparation of Small Yellow Ginger Compound

[0053] Take the obtained small yellow ginger and dried tangerine peel extracts, mix them respectively according to mass ratios of 3:1, 2:1, 1:1, 1:2, and 1:3, and prepare gradient - concentration small yellow ginger - dried tangerine peel compound solutions with primary water.

[0054] Take the obtained small yellow ginger and hawthorn extracts, mix them respectively according to mass ratios of 3:1, 2:1, 1:1, 1:2, and 1:3, and prepare gradient - concentration small yellow ginger - hawthorn compound solutions with primary water.

[0055] Example 2: Determination of the Optimal Compound Mass Ratio of Small Yellow Ginger Extract and Compound Components

[0056] 1. α - Glucosidase Activity Inhibition Test Method

[0057] Add 50 μL of sample solutions with different concentrations and 50 μL of α-glucosidase working solution into a 96-well plate in sequence, incubate at 37 °C for 15 min, then add 50 μL of pNPG working solution, continue to incubate at 37 °C for another 15 min, and finally add 100 μL of 0.2 mol / L Na2CO3 solution to terminate the reaction. Measure the absorbance value A1 of the reaction solution at 405 nm; use 50 μL of PBS buffer to replace the α-glucosidase working solution and the sample solution respectively as the sample control group and the blank group; use 100 μL of PBS to replace the sample solution and the α-glucosidase working solution as the blank control group. The calculation formula for the inhibition rate of the α-glucosidase activity of the sample solution is shown in the formula:

[0058]

[0059] In the formula, A1 is the absorbance value of the sample solution, α-glucosidase and pNPG; A2 is the absorbance value of the sample solution, PBS and pNPG; A3 is the absorbance value of α-glucosidase, PBS and pNPG; A4 is the absorbance value of PBS and pNPG.

[0060] 2. Isobolographic method

[0061] The isobolographic method is a technique used to evaluate the interaction of active ingredients. It was initially proposed by Fraser in 1870 and further improved by Loewe in 1928. This method evaluates the interaction between active ingredients by comparing the doses when two active ingredients are used in combination with the doses required to achieve the same effect when used alone. In the experiment, first determine the doses of active ingredient A and active ingredient B that individually produce a half-maximal effect (A 50 and B 50 ), and draw an additive isobole connecting these two points. When the combined dose ratio point is on the isobole, it indicates an additive effect between the active ingredients; if it is below the isobole, it shows a synergistic effect; if it is above the isobole, it is an antagonistic effect. For points close to the isobole, the nature of their effects needs to be further evaluated by statistical methods (such as confidence interval analysis).

[0062] 3. Median-effect principle

[0063] To evaluate the dose-effect relationship of the extracts of Zingiber officinale Rosc. var. xiaoheijiang, Citrus reticulata Blanco and Crataegus pinnatifida Bunge, and to determine whether the compound has a synergistic effect, the present invention is based on the Chou-Talalay median-effect principle and quantifies the synergistic effect through the Combination Index (CI).

[0064] The definition formula of the median-effect principle is:

[0065]

[0066] Where D is the dose; D m is the dose required for 50% inhibition rate; f a is the effect corresponding to the dose D; m is the dose-effect curve coefficient.

[0067] The formula definition of the combination index is:

[0068]

[0069] Where D1 and D2 are the concentrations of the two components in the compound needed to reach 50% inhibition rate, D x1 , D x2 is the half inhibitory concentration (IC 50 ) of a single component. The judgment criteria adjusted according to experimental error: CI < 0.9, CI = 0.9 - 1.1, and CI > 1.1 indicate that the compound has synergistic, additive, and antagonistic effects respectively.

[0070] 4. Determination of IC 50 of the activities of α-glucosidase by extracts of small yellow ginger and compound components

[0071] Prepare solutions of extracts of small yellow ginger, tangerine peel, and hawthorn with gradient concentrations respectively, and measure the inhibition rate of α-glucosidase according to the method described above. Calculate the IC 50 of the inhibitory effects of different extracts on α-glucosidase according to the measurement results.

[0072] 5. Determination of the optimal compound mass ratio of the extract of small yellow ginger and compound components

[0073] Compound the extract of small yellow ginger with different compound components according to the mass ratios of 3:1, 2:1, 1:1, 1:2, and 1:3 respectively, and measure the inhibition rate of α-glucosidase with reference to the method described above.

[0074] 6. Determination of IC 50 of each component when the extract of small yellow ginger is compounded with compound components

[0075] Prepare solutions with gradient concentrations according to the obtained optimal mass ratio, and calculate the IC 50 of each of the extract of small yellow ginger and the two substances when compounded. Substitute them into the combination index calculation formula to calculate the combination index (CI) of the compound of the extract of small yellow ginger and the two extracts, and judge whether the extract of small yellow ginger and the two plant extracts have synergistic effects according to the CI value.

[0076] Results:

[0077] (1) Determination of IC 50 of the activities of α-glucosidase by extracts of small yellow ginger and compound components

[0078] With the increase in the concentrations of the extracts of small yellow ginger, tangerine peel, and hawthorn, the inhibition rate of α-glucosidase also gradually increases, showing a positive dose-effect relationship. Figure 1 ) It was calculated that the IC 50 values of the extracts of small yellow ginger, tangerine peel, and hawthorn for α-glucosidase were 0.436 mg / mL, 0.122 mg / mL, and 0.156 mg / mL, respectively. This indicates that all three extracts can preferably inhibit the activity of α-glucosidase and have good potential for treating diabetes.

[0079] (2) Determination of the compound mass ratios of the extract of small yellow ginger with the extracts of tangerine peel and hawthorn

[0080] When the extract of small yellow ginger is compounded alone or with the extracts of tangerine peel and hawthorn according to the following mass ratios, the inhibition rates of α-glucosidase are as Figure 2 shown.

[0081] When the extract of small yellow ginger is compounded alone or with the extract of tangerine peel, the order of the mass ratios sorted by the inhibition rate is: 1:2 > 1:3 > DTPE > 1:1 > 3:1 > 2:1 > GE. Among them, when the compound mass ratios are 1:2 and 1:3, the inhibition rates are both higher than those of the individual samples. When the mass ratio is 1:1, there is no significant difference from the effect of the extract of tangerine peel alone. When compounded with the extract of hawthorn alone or in combination, the order of the mass ratios sorted by the inhibition rate is: 1:3 > CPE > 1:2 > 1:1 > 2:1 > 3:1 > GE. Among them, when the compound mass ratio is 1:3, the inhibition rate is higher than that of the individual sample. When the mass ratio is 1:2, there is no significant difference from the effect of the extract of hawthorn alone. To further explore the synergistic effect, the extract of small yellow ginger is compounded with the extract of tangerine peel (1:1, 1:2, 1:3) and the extract of hawthorn (1:2, 1:3) according to the selected mass ratios, and the IC 50 synergistic effect determination is carried out with this as the experimental group.

[0082] (3) Calculation of the combination index

[0083] To evaluate the synergistic effect, according to the optimized ratio, the present invention compounds two compound components with the extract of small yellow ginger into a gradient concentration system and systematically measures its IC 50 value. With the total concentration of the compound as X and the inhibition rate as Y, a dose-effect curve is plotted, and the results are as Figure 3 shown.

[0084] Table 1 and Figure 4 are the IC 50Value and isoeffect contour plot. The results showed that the dose ratio points of the compound GE:DTPE = 1:2, GE:CPE = 1:2, and GE:CPE = 1:3 were all below the isoeffect contour, indicating a synergistic effect between Zingiber officinale Rosc. and the extracts of Citrus reticulata Blanco and Crataegus pinnatifida Bunge on α-glucosidase activity inhibition; the dose ratio point of the compound GE:DTPE = 1:1 was within the 95% confidence interval, showing an additive effect; the dose ratio point of the compound GE:DTPE = 1:3 was above the isoeffect contour, showing an antagonistic effect. As shown in Table 1, when the extracts of Zingiber officinale Rosc. and Citrus reticulata Blanco were compounded, only the 1:2 ratio achieved a synergistic effect (CI = 0.759), and the other ratios (1:1, CI = 0.969; 1:3, CI = 1.07) only showed an additive effect because the CI values were between 0.9 and 1.1; when Zingiber officinale Rosc. was compounded with the extract of Crataegus pinnatifida Bunge, significant synergistic effects (CI < 0.9) were shown at the 1:2 and 1:3 ratios, and the results were consistent with those of the isoeffect diagram method.

[0085] The α-glucosidase inhibition experiment showed that the composite extracts with different ratios all had a dose-dependent inhibitory effect, but the synergistic effect evaluation showed that synergistic enhancement was only observed in the composite systems of Zingiber officinale Rosc.-Citrus reticulata Blanco (1:2), Zingiber officinale Rosc.-Crataegus pinnatifida Bunge (1:2 and 1:3). Based on the verification results of the synergistic effect, these optimized ratios were finally selected for in-depth study.

[0086] Table 1 IC 50 and CI values

[0087]

[0088]

[0089] Determination criteria for the synergistic index (CI): CI < 0.9 indicates a synergistic effect, CI = 0.9 - 1.1 indicates an additive effect, and CI > 1.1 indicates an antagonistic effect.

[0090] Example 3: Study on the hypoglycemic activity of the extract of Zingiber officinale Rosc. and its compound based on the HepG2 cell model

[0091] 1. Cell culture and determination of cell viability

[0092] The cell toxicity experiment of the extract of Zingiber officinale Rosc. and its compound was determined by the MTT method. HepG2 cells were placed in DMEM medium containing 10% FBS and 1% penicillin-streptomycin and cultured in a cell incubator at 37°C and 5% CO2. The HepG2 cell suspension was added at 100 μL per well (cell density 1 × 10 4Cells / well were inoculated into 96-well plates and cultured at 37 °C for 24 h. Then, 100 μL of medium containing samples at different concentrations (25 - 400 μg / mL) was added to each well and cultured for another 24 h. Subsequently, 100 μL of 0.5 mg / mL MTT prepared with fresh medium was added to each well and cultured for 4 h. Finally, 100 μL of dimethyl sulfoxide (DMSO) was added to dissolve the blue-violet crystals, and the mixture was shaken for 10 min. The absorbance was measured at 490 nm to calculate the cell survival rate.

[0093] 2. Effects of extracts and compound of Zingiber officinale Rosc. var. xiao on glucose consumption of IR-HepG2 cells

[0094] The experiments were divided into a normal group (without adding the inducer GluN (glucosamine)), a model group (adding the inducer GlnN), and an experimental group (adding the inducer GlnN and the sample). HepG2 cells were inoculated into 96-well plates at 100 μL per well (cell density 1×10 4 cells / well) and cultured for 24 h. Then the supernatant was aspirated, and the cells were washed twice with PBS buffer. The normal group was added with complete medium without GluN, while the model group and the experimental group were added with complete medium containing 18 mmol / L GluN and cultured for 24 h. The cells were washed twice with PBS. The normal group and the model group were added with 100 μL of DMEM complete medium, and the experimental group was added with 100 μL of DMEM complete medium containing the sample. After culturing for 24 h, the supernatant was collected, and the glucose concentration in the supernatant was measured using a glucose oxidase kit.

[0095] 3. Effects of extracts and compound of Zingiber officinale Rosc. var. xiao on glycogen content of IR-HepG2 cells

[0096] The cell culture method was the same as above. Cells were inoculated into 24-well plates at 4×10 5 cells / mL, with an inoculation volume of 500 μL per well. After culturing for 24 h, the culture medium in each well was discarded, 200 μL of trypsin was added to digest for 3 min, and then 2-fold volume of complete medium was added to terminate the digestion. The cells were centrifuged at 15000 rpm / min for 10 min, and the cell pellet was collected. The glycogen content was measured using a glycogen kit (Nanjing Jiancheng, A043).

[0097] Results:

[0098] (1) Effects of extracts and compound of Zingiber officinale Rosc. var. xiao on the viability of HepG2 cells

[0099] As Figure 5As shown in Figure A, compared with the normal control group, within the concentration range of 12.5 - 800 μg / mL, the extracts of Zingiber officinale Rosc., the compound of Zingiber officinale Rosc. and Citrus reticulata Blanco (1:2), the compound of Zingiber officinale Rosc. and Crataegus pinnatifida Bunge (1:2), and the compound of Zingiber officinale Rosc. and Crataegus pinnatifida Bunge (1:3) had no significant effect on the activity of HepG2 cells. Therefore, we selected the extracts of Zingiber officinale Rosc. and their compounds within the above concentration range to determine their regulatory effects on the functions related to glucose metabolism of IR-HepG2 cells.

[0100] (2) Effects of the extracts of Zingiber officinale Rosc. and their compounds on the glucose consumption of IR-HepG2 cells

[0101] The level of glucose consumption is an important indicator for evaluating cell metabolic activity and glucose utilization ability. As Figure 5 shown in Figure B, in the model group of IR-HepG2 cells induced by glucosamine, the glucose consumption was significantly lower than that of the normal control group (P<0.001), indicating successful modeling. For IR-HepG2 cells, the addition of the extracts of Zingiber officinale Rosc. and their compounds and acarbose increased the glucose consumption level of IR-HepG2 cells in a concentration-dependent manner. Compared with the group treated with the extract of Zingiber officinale Rosc. alone, the glucose consumption in the groups treated with the compound of Zingiber officinale Rosc. and Citrus reticulata Blanco (1:2), the compound of Zingiber officinale Rosc. and Crataegus pinnatifida Bunge (1:2), and the compound of Zingiber officinale Rosc. and Crataegus pinnatifida Bunge (1:3) increased significantly. This indicates that these compounds may play a synergistic role in enhancing the glucose uptake and metabolism ability of IR-HepG2 cells. Among them, compared with the model group, at 400 μg / mL, the glucose consumption of IR-HepG2 cells in the groups treated with the extract of Zingiber officinale Rosc., the compound of Zingiber officinale Rosc. and Citrus reticulata Blanco (1:2), the compound of Zingiber officinale Rosc. and Crataegus pinnatifida Bunge (1:2), and the compound of Zingiber officinale Rosc. and Crataegus pinnatifida Bunge (1:3) increased by 16.86%, 18.09%, 22.51%, and 18.97% respectively.

[0102] (3) Effects of the extracts of Zingiber officinale Rosc. and their compounds on the glycogen content of IR-HepG2 cells

[0103] Glycogen synthesis is the core process for regulating blood glucose homeostasis. In normal hepatocytes, insulin inhibits GSK-3β through the PI3K / Akt pathway, relieving its inhibitory effect on glycogen synthase (GS) (dephosphorylation of Ser641), thereby promoting glycogen storage. However, in IR-HepG2 cells, due to abnormal serine phosphorylation of insulin receptor substrate-1 (IRS-1), the activation of Akt is blocked, and the activity of GS is continuously inhibited. As Figure 5As shown in C, the glycogen synthesis in the IR-HepG2 cell model group was significantly lower than that in the normal control group (P<0.001). The extract of small yellow ginger, its compound preparations and acarbose could improve the glycogen synthesis in IR-HepG2 cells. Among them, the glycogen synthesis in the treatment groups of small yellow ginger - tangerine peel compound (1:2), small yellow ginger - hawthorn compound (1:2) and small yellow ginger - hawthorn compound (1:3) was higher than that of the small yellow ginger extract alone, which was consistent with the results of glucose consumption. The experimental results showed that the extract of small yellow ginger, its compound preparations and acarbose might improve the glycogen synthesis ability by repairing the IRS-1 / Akt signal transduction or directly regulating the phosphorylation state of GS, thereby alleviating the metabolic disorders related to insulin resistance.

[0104] Example 4: Study on the hypoglycemic activity of the extract of small yellow ginger and its compound preparations based on the nematode model

[0105] 1. Cultivation and synchronization of nematodes

[0106] NGM medium: containing 1.5 g NaCl, 8 g Agar, 1.25 g peptone, 0.1 g Streptomycin, 487.5 mL of primary water, sterilized at 121 °C for 30 min and kept at 80 °C for 15 min. Add 0.5 mL of 5 mg / mL cholesterol (dissolved in absolute ethanol) sterilized by filter membrane, 0.5 mL of 1 mmol / L CaCl2, 0.5 mL of 1 mmol / L MgSO4, and 12.5 mL of PBS buffer solution with pH 6.0. LB liquid medium: containing 2.1 g of LB medium and 100 mL of primary water, sterilized in the same way as NGM medium.

[0107] 1 mmol / L potassium phosphate buffer solution with pH 6.0: containing 54.195 g of KH2PO4, 17.8465 g of K2HPO4, and 500 mL of primary water. M9 buffer solution: containing 3 g of Na2HPO4, 1.5 g of KH2PO4, 2.5 g of NaCl, 0.125 g of MgSO4·7H2O, and 500 mL of primary water, sterilized at 121 °C for 15 min.

[0108] Cultivation of nematodes: Inoculate 100 μL of E. coli OP50 bacterial solution into 100 mL of LB liquid medium, culture at 37 °C and 170 rpm for 12 h, take it out and store it in the refrigerator at 4 °C for later use. Pipette 200 μL of E. coli OP50 bacterial solution onto the NGM plate, place it at room temperature for 2 days and then store it in the refrigerator at 4 °C for later use. Inoculate the agar medium block containing a large number of nematodes onto the plate and culture it at a constant temperature of 20 °C.

[0109] Nematode synchronization: Adult nematodes were transferred from NGM medium to 2 mL Eppendorf tubes with M9 buffer, centrifuged at 3000 rpm for 2 min. After discarding the supernatant, 1 mL of M9 buffer and 1 mL of sodium hypochlorite lysis solution were added, and vortexed rapidly for several times until the worms were fully lysed. Then centrifuged at 3000 rpm for 2 min, and the precipitate was washed with M9 buffer 3 - 5 times until there was no chlorine smell. Then the precipitate was resuspended with a small amount of M9, and then cultured in an incubator at 20 °C for 12 h to obtain L1 larvae.

[0110] 2. Establishment of the high - glucose model of nematodes

[0111] The glucose solution and E. coli OP50 bacterial solution were mixed at a ratio of 1:9 to prepare a 50 mmol / L glucose solution, which was evenly coated on the NGM medium. The synchronized L1 nematodes were transferred to the medium, and their glucose content was measured after 60 h. Whether the high - glucose model of nematodes was successful was determined according to the glucose content.

[0112] 3. Grouping of nematode experiments

[0113] The experiments were divided into a normal group, a model group, and a sample group (50, 100, and 200 μg / mL). The sample solution was prepared with a glucose solution. The sample and E. coli OP50 bacterial solution were mixed at a ratio of 1:9, coated on the NGM medium, and air - dried at room temperature (22 - 25 °C) in a sterile operating hood for 4 h until the liquid film disappeared, then stored at 4 °C. The normal group and the model group were replaced with sterilized first - grade water instead of the sample. After the synchronized L1 larvae were transferred to the NGM plate with food and cultured for 60 h, the nematodes in each group could be processed according to the test requirements.

[0114] 4. Determination of physiological and biochemical indexes

[0115] After the nematodes were treated, they were collected with M9 buffer into 2 mL centrifuge tubes and washed 3 times with M9 buffer. Fresh M9 buffer and grinding beads were added and ground thoroughly. Centrifuged at 12000 rpm / min for 10 min at 4 °C, and the supernatant was transferred to a new centrifuge tube. The protein concentration, glucose, triglyceride, malondialdehyde, total glutathione content, and total superoxide dismutase activity of the supernatant were measured according to the instructions of the commercial kit. The results were normalized to the protein level.

[0116] 5. Oil Red O staining

[0117] The nematodes at the end of the drug administration treatment were collected into a 2 mL centrifuge tube and washed 3 times with M9 buffer. After being washed clean, an appropriate amount of paraformaldehyde was added, and they were fixed at room temperature for 30 min. After being washed 3 times with M9 buffer, an appropriate amount of Oil Red O staining solution was added, and they were stained at room temperature in the dark for 1 h. After the staining was completed, they were washed several times with M9 buffer, and a small amount of liquid was left. An appropriate amount of 0.01% Triton-X100 was added, and the nematodes were observed under a microscope and photographed. The Image J software was used to analyze and count the staining results of the nematodes.

[0118] 6. Data analysis

[0119] The experimental data of each group were processed by SPSS 26.0 software, and the test results were expressed as mean±SD. The significance between groups was analyzed by one-way analysis of variance (Duncan's test in One-AVOVA). P<0.05 indicates a significant difference. Excel 2021 and Origin 2021 were used to statistically analyze the data and draw charts.

[0120] Results:

[0121] (1) Effects of Zingiber officinale Rosc. extracts and their complexes on the antioxidant capacity of N2 nematodes under high glucose conditions

[0122] Oxidative stress plays a key role in the occurrence and development of diabetes by promoting insulin resistance and β-cell dysfunction; at the same time, hyperglycemia and lipid metabolism disorders related to diabetes can further exacerbate the accumulation of reactive oxygen species (ROS), forming a self-perpetuating vicious cycle. Glutathione (GSH) is a tripeptide containing a sulfhydryl group (-SH) synthesized by cells themselves. By directly neutralizing lipid peroxides (such as MDA) and regenerating vitamin E, it becomes a core molecule of the antioxidant defense system. In addition, the GSH-dependent glutathione peroxidase (GPx) pathway can regulate immune signals such as NF-κB to maintain cellular redox homeostasis. Excessive ROS induces the accumulation of malondialdehyde (MDA) through lipid peroxidation reaction, and the latter can promote tumorigenesis, metabolic disorders and reduce membrane fluidity. As the end product of lipid peroxidation, the concentration of MDA is positively correlated with oxidative stress damage and is a reliable marker for evaluating the level of oxidative damage. Superoxide dismutase (SOD) is the core enzyme that regulates the redox homeostasis of the body. By catalyzing the conversion of superoxide anion (O2 - ) into hydrogen peroxide (H2O2) and oxygen (O2), it specifically scavenges free radicals. Its activity synergizes with the cellular antioxidant defense network (such as the glutathione system) and can significantly reduce DNA and lipid damage induced by oxidative stress. Such as Figure 6As shown, after high-glucose treatment, the GSH content in nematodes decreased significantly (P<0.001), while the MDA content and SOD activity increased significantly (P<0.001). The extracts of Zingiber officinale Rosc. and their compound preparations could increase the GSH level of nematodes treated with high glucose to varying degrees, and decrease the MDA content and SOD activity. Compared with the high-glucose treatment group, at a concentration of 200 μg / mL, the extracts of Zingiber officinale Rosc., the compound preparation of Zingiber officinale Rosc. and Citrus reticulata Blanco (1:2), the compound preparation of Zingiber officinale Rosc. and Crataegus pinnatifida Bunge (1:2), and the compound preparation of Zingiber officinale Rosc. and Crataegus pinnatifida Bunge (1:3) could increase the GSH level by 17.05%, 57.68%, 69.89%, and 64.27% respectively, decrease the MDA content by 13.87%, 23.04%, 37.43%, and 29.29% respectively, and decrease the SOD activity by 21.66%, 32.52%, 46.99%, and 35.07% respectively. The experimental results showed that the extracts of Zingiber officinale Rosc. and their compound preparations had a dual mechanism for scavenging ROS: one was the direct antioxidant effect of the active ingredients; the other was possibly to activate the Nrf2 / ARE signaling pathway, up-regulate the SOD activity and GSH content, and inhibit the generation of lipid peroxidation products such as MDA. This synergistic effect was consistent with the classical mode of the Nrf2 pathway regulating the endogenous antioxidant defense system, suggesting that the samples could alleviate oxidative damage through multi-target intervention.

[0123] (2) Effects of extracts of Zingiber officinale Rosc. and their compound preparations on the glucose level of N2 nematodes under high-glucose environment

[0124] Under high-glucose conditions, the glucose level in nematodes was 0.82 times higher than that in the normal control group ( Figure 7 in A), indicating that glucose could enter nematodes through the body surface penetration or feeding pathway to drive metabolic activities, and the addition of the extracts of Zingiber officinale Rosc. and their compound preparations reduced the glucose accumulation in nematodes and effectively alleviated the metabolic imbalance induced by high glucose. Compared with the high-glucose treatment group, at a concentration of 200 μg / mL, the extracts of Zingiber officinale Rosc., the compound preparation of Zingiber officinale Rosc. and Citrus reticulata Blanco (1:2), the compound preparation of Zingiber officinale Rosc. and Crataegus pinnatifida Bunge (1:2), and the compound preparation of Zingiber officinale Rosc. and Crataegus pinnatifida Bunge (1:3) could reduce the glucose level in nematodes by 36.39%, 54.71%, 66.10%, and 56.21% respectively.

[0125] (3) Effects of extracts of Zingiber officinale Rosc. and their compound preparations on the fat level of N2 nematodes under high-glucose environment

[0126] There is a two-way regulatory relationship in glycolipid metabolism disorders. Acute energy overload can trigger the abnormal activation of the key transcription factor of lipogenesis (SREBP-1c) and induce metabolic imbalance through the PI3K / Akt pathway disorder. Due to the transparent body wall characteristics of Caenorhabditis elegans, lipid visualization detection can be achieved by osmotic staining with the fat-soluble dye Oil Red O. By observing the staining intensity and distribution characteristics under a microscope, the nutritional status and lipid metabolism dynamics of organisms can be quantitatively evaluated, which is a classic model for studying lipid metabolism. As Figure 8 and Figure 7 shown in B and C, the red color of the nematodes in the high-glucose treatment group was significantly darker than that of the nematodes in the normal control group, and the fat content increased. At the same time, the triglyceride content in the nematodes of the high-glucose treatment group increased significantly (P<0.001). When the nematodes treated with high glucose were fed different contents of Zingiber officinale extracts and their compound preparations, the lipid content in the nematodes decreased to varying degrees, the color of the red area of the nematodes became lighter and the covered area decreased significantly, and the triglyceride level in the body also gradually decreased. Compared with the high-glucose treatment group, at a concentration of 200 μg / mL, the Zingiber officinale extract, the Zingiber officinale-Citrus reticulata compound preparation (1:2), the Zingiber officinale-Crataegus pinnatifida compound preparation (1:2), and the Zingiber officinale-Crataegus pinnatifida compound preparation (1:3) could reduce the glucose level in the nematodes by 32.12%, 43.76%, 56.43%, and 48.78% respectively, indicating that the Zingiber officinale extract and its compound preparations also have a positive regulatory effect on lipid metabolism.

[0127] The above embodiments are the preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. The use of a turmeric extract or a compound thereof in the preparation of a blood sugar lowering product, characterized in that: The compound is a compound of turmeric extract and tangerine peel extract, or a compound of turmeric extract and hawthorn extract.

2. The use of the Zingiber officinale extract or its compound according to claim 1 in the preparation of a hypoglycemic product, characterized in that: The blood sugar lowering product is a food that helps maintain a healthy blood sugar level, a health product that helps maintain a healthy blood sugar level, or a blood sugar lowering drug.

3. The use of the Zingiber officinale extract or its compound according to claim 1 or 2 in the preparation of a blood sugar-lowering product, characterized in that: In the compound of the turmeric extract and the tangerine peel extract, the ratio of the turmeric extract to the tangerine peel extract is 1:1.5-2.5, preferably 1:

2.

4. The use of the Zingiber officinale extract or its compound according to claim 1 or 2 in the preparation of a blood sugar-lowering product, characterized in that: In the compound of the turmeric extract and the hawthorn extract, the ratio of the turmeric extract to the hawthorn extract is 1:1.5-3.5; preferably 1:2 or 1:

3.

5. The use of the Zingiber officinale extract or its compound according to claim 1 or 2 in the preparation of a blood sugar-lowering product, characterized in that: The hypoglycemic product is a hypoglycemic drug, and also contains other pharmaceutically acceptable carriers or excipients to be made into a pharmaceutically acceptable dosage form.

6. Use of the Zingiber officinale extract or its compound according to claim 1 or 2 in the preparation of a blood sugar-lowering product, characterized in that: The turmeric extract is prepared by the following steps: weighing turmeric powder, adding ethanol solution, ultrasonic treatment, suction filtration, centrifugal treatment of the filtrate, concentrating the supernatant, freeze-drying, and refrigerating for later use; The tangerine peel extract and hawthorn extract are prepared by the following steps: weighing tangerine peel or hawthorn powder, mixing with water, extracting with hot water, filtering, collecting supernatant by centrifugation, extracting the residue once again according to the above method, vacuum concentrating, and freeze-drying to obtain tangerine peel or hawthorn extract.

7. The use of the Zingiber officinale extract or its compound according to claim 6 in the preparation of a blood sugar-lowering product, characterized in that: The ethanol solution is 50wt% to 90wt% ethanol solution; The ratio of the small yellow turmeric powder to the ethanol solution is 1g:15-20mL; The ultrasonic treatment conditions are 45-55°C, 80-120W, 30-35min; The concentration is concentrated at 45-55°C; The ratio of the tangerine peel extract or hawthorn extract to water is 1g:5-20mL; The hot water extraction conditions are 85-95° C., 1-3 h; The centrifugal conditions are 3000-5000 rpm, 5-15 min; The vacuum concentration is vacuum concentration at 55-65°C.

8. The use of the Zingiber officinale extract or its compound according to claim 6 in the preparation of a blood sugar-lowering product, characterized in that: The ethanol solution is a 71wt% ethanol solution; The ratio of the small yellow turmeric powder to the ethanol solution is 1g:19mL; The ultrasonic treatment conditions are 50°C, 100W, 32min; The ratio of the tangerine peel extract or hawthorn extract to water is 1g:10mL; The hot water extraction conditions are 90° C. and 2 h.

9. A hypoglycemic composition, characterized in that: The invention is composed of the following components in parts by weight: 1 part of turmeric extract and 1.5-2.5 parts of tangerine peel extract, or 1 part of turmeric extract and 1.5-3.5 parts of hawthorn extract.

10. The hypoglycemic composition according to claim 9, characterized in that: The invention is composed of the following components in parts by mass: 1 part of turmeric extract and 2 parts of tangerine peel extract, or 1 part of turmeric extract and 3 parts of hawthorn extract.