A composition for helping to maintain healthy blood sugar levels, and methods of making and using the same

Abstract

The present application relates to a composition for maintaining healthy blood sugar level and its preparation method and application, and belongs to the technical field of health products. The composition for maintaining healthy blood sugar level comprises mulberry leaf extract, cactus extract, prunus domestica extract, glyceryl tributyrate and capsaicin. The present application has the beneficial effect of providing a composition of active ingredients which can effectively reduce the level of cortisol, significantly reduce the blood sugar level, and protect the activity of pancreatic beta cells. The composition is good for restoring insulin sensitivity and controlling weight. The present combination formula is reasonable, the product performance is stable, the preparation is simple, and the industrialized production is easy to realize.

Description

Technical Field

[0001] This invention relates to the field of health product technology, and in particular to a composition that helps maintain healthy blood sugar levels, its preparation method, and its application. Background Technology

[0002] With changes in global lifestyles and dietary structures, diabetes has become a major chronic metabolic disease seriously affecting human health. Its core pathological mechanism centers on an imbalance in blood glucose homeostasis, manifesting as a persistent state of hyperglycemia. Scientific research has confirmed that this metabolic disorder is directly linked to a dual pathological basis of impaired pancreatic β-cell function and decreased insulin sensitivity.

[0003] As the sole functional unit for insulin secretion, pancreatic β-cells, when damaged or with reduced activity, directly lead to absolute or relative insulin deficiency. Simultaneously, insulin resistance in peripheral tissues (such as skeletal muscle, liver, and adipose tissue) exacerbates glucose uptake and utilization disorders. This dual effect creates a "hyperglycemic toxicity" environment, further accelerating β-cell apoptosis, thus constituting a vicious cycle.

[0004] Furthermore, recent studies have found that chronic stress-induced abnormally elevated cortisol levels (overactivation of the hypothalamic-pituitary-adrenal axis / HPA axis) have become a significant contributing factor to glycemic instability. On one hand, cortisol inhibits insulin gene transcription and reduces insulin synthesis by activating glucocorticoid receptors (GR); on the other hand, cortisol-driven chronic hyperglycemia induces endoplasmic reticulum stress and increases oxidative damage to β-cell mitochondria. Therefore, lowering cortisol levels is crucial for blood glucose control.

[0005] However, traditional drug interventions and treatments currently have certain limitations and side effects. For example, metformin is currently the most commonly used first-line drug for controlling blood sugar. It lowers fasting blood sugar by inhibiting hepatic gluconeogenesis and output, but it may cause significant gastrointestinal reactions such as nausea, vomiting, and decreased appetite, and long-term use may lead to problems such as vitamin B deficiency. In addition, drugs targeting GLP-1 (glucagon-like peptide-1) receptor agonists, such as liraglutide and semaglutide, are also used to treat type 2 diabetes and obesity. Although they can help lower blood sugar and reduce weight, they not only cause side effects such as decreased appetite and low mood, but also, with increasing clinical studies finding that GLP-1 receptor agonists may cause muscle loss, hair loss, and pancreatitis, these problems have attracted the attention of the medical community. Furthermore, long-term use of GLP-1 receptor agonists may increase the risk of medullary thyroid carcinoma, although this is very rare, it reminds doctors and patients to weigh the benefits of treatment against the potential risks.

[0006] Besides the aforementioned medications, other common blood sugar-controlling ingredients on the market, such as white kidney bean extract, mulberry leaf extract, and L-arabinose, also have certain limitations. For example, white kidney bean extract, as an α-amylase inhibitor, can only block the breakdown of starch into glucose and reduce sugar absorption; its effect on controlling blood sugar in other carbohydrates is not significant. Mulberry leaf extract is an α-glucosidase inhibitor, requiring not only a relatively high daily intake but also affecting the intake of fat-soluble vitamins (such as vitamins D and K). L-arabinose can only inhibit sucrase activity, is almost ineffective at low doses, and can easily cause osmotic diarrhea at high doses. These blood sugar-controlling and fat-reducing ingredients target fewer carbohydrates, cannot protect pancreatic β-cells, and cannot regulate cortisol levels; therefore, their mechanisms of action are relatively simple, and their blood sugar-controlling effects are not ideal.

[0007] In recent years, many studies abroad have shown that plant extracts such as cactus extract, mulberry leaf extract, and capsaicin have demonstrated the effects of controlling blood sugar and regulating weight. However, it is unclear whether they can regulate hormone levels and protect insulin cells, and the effective concentration ratios among various plant extracts are still unknown.

[0008] Currently, numerous studies have reported on the use of animal models to study diabetes and obesity and their complications. Among these studies, the most commonly used animal models are rats, mice, pigs, and monkeys. Each animal model has its advantages and disadvantages, and no single animal model can fully represent the clinical symptoms of human diabetes. Zebrafish models, due to their numerous advantages not possessed by other model organisms, have gradually gained attention from many researchers and become a very important vertebrate model organism. First, zebrafish are easy to breed due to their small size, large number of eggs, short growth cycle, transparent development, and simple adult reproduction, which can effectively improve experimental efficiency and is suitable for large-scale experimental research. Second, the genetic information of zebrafish is well-documented, and gene manipulation techniques are mature. By targeting and inducing or knocking out certain genes and altering their expression levels, some human disease states can be easily expressed in zebrafish. Therefore, zebrafish are very suitable for modeling and studying the mechanisms of human diseases. Most importantly, zebrafish models have unique characteristics and advantages in endocrine gland function and glucose metabolism, and this model has been applied to the study of metabolic diseases such as diabetes and obesity in humans.

[0009] Given the shortcomings of the existing technologies, it is necessary to find a safer and more effective composition that lowers blood sugar and cortisol levels while effectively protecting pancreatic β cells through zebrafish testing systems, in order to reduce or avoid the potential side effects of existing drugs and methods. Summary of the Invention

[0010] The purpose of this invention is to overcome the shortcomings of the prior art and provide a composition that helps maintain healthy blood sugar levels, as well as its preparation method and application.

[0011] To achieve the above objectives, the technical solution adopted by the present invention is as follows: In a first aspect, the present invention provides a composition that helps maintain healthy blood sugar levels, comprising mulberry leaf extract, cactus extract, apricot kernel extract, capsaicin, and tributyric acid glyceride in a mass ratio of 1:5-10:5-7:1-5:1-5.

[0012] The present invention obtains a composition by selecting a specific mass ratio of mulberry leaf extract, cactus extract, apricot kernel extract, capsaicin, and tributyric acid glyceride, which has a significant effect on maintaining healthy blood sugar levels.

[0013] Preferably, the composition comprises mulberry leaf extract, cactus extract, apricot kernel extract, capsaicin, and glyceryl tartrate in a mass ratio of 1:7:6:3:2.

[0014] The present invention has found that the combination of mulberry leaf extract, cactus extract, apricot kernel extract, capsaicin, and tributyric acid glyceride in the above-mentioned specific mass ratio has a significant effect on maintaining healthy blood sugar levels and can effectively regulate cortisol levels and protect insulin cells.

[0015] In a second aspect, the present invention provides the use of the composition described in the first aspect in the preparation of health products that help maintain healthy blood sugar levels.

[0016] Preferably, the health product dosage form is any one of powder, ointment, pill, tablet, capsule, or oral liquid.

[0017] Thirdly, the present invention provides a capsule that helps maintain healthy blood sugar levels, the capsule containing the composition described in the first aspect that helps maintain healthy blood sugar levels.

[0018] Preferably, the capsule also includes excipients acceptable for health supplements.

[0019] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention provides a composition comprising mulberry leaf extract, cactus extract, apricot kernel extract, capsaicin, and tributyric acid glyceride. Studies have found that, under specific ratios, this composition can synergistically lower blood sugar, regulate cortisol levels, and protect pancreatic β-cells. Its possible mechanism of action is as follows: Mulberry leaf extract: Rich in polyphenolic compounds, it possesses antioxidant and anti-inflammatory properties. It helps scavenge free radicals, reduce oxidative stress damage to pancreatic β-cells, and assists in improving glucose metabolism by regulating gut microbiota.

[0020] Cactus extract: Contains flavonoids and polysaccharides, which help improve insulin sensitivity and inhibit excessive glycogenolysis. Furthermore, it may help alleviate stress responses by regulating the HPA axis (hypothalamic-pituitary-adrenal axis).

[0021] Prunus japonica seed extract: Traditionally used to promote metabolism, its active ingredients may help regulate lipid metabolism and reduce metabolic stress.

[0022] Capsaicin: It promotes energy consumption and enhances glucose uptake by activating TRPV1 receptors, and also has a certain anti-inflammatory effect.

[0023] Tributyrate: As a precursor to butyric acid (a short-chain fatty acid), it can release butyric acid in the intestine, thereby helping to protect the integrity of the intestinal barrier, inhibit intestinal inflammation, and indirectly participate in regulating the levels of glucocorticoids such as cortisol through the gut-brain axis.

[0024] Synergistic effect mechanism integration: The combination of these five ingredients may produce synergistic effects through multiple targets and pathways: Synergistic metabolism and absorption: The gut health environment maintained by tributyrate may enhance the absorption and utilization of other active ingredients; capsaicin-promoted blood circulation may accelerate the distribution and metabolism of various components.

[0025] Anti-inflammatory and antioxidant network: The antioxidant effects of mulberry leaf and cactus extracts, combined with the anti-inflammatory pathways of capsaicin and tributyrate, work together to reduce inflammation and oxidative damage in pancreatic tissue, providing complex protection for β cells.

[0026] The combined regulation of endocrine and metabolic functions: the regulation of the HPA axis by cactus extract and the gut-brain axis effect of tributyric acid glyceride, supplemented by the metabolic balance of Prunus japonica seed extract, synergistically regulate blood glucose and stress hormone levels from multiple dimensions.

[0027] In summary, the composition provided by this invention constructs a multi-target, multi-pathway synergistic network through the combination of mulberry leaf extract, cactus extract, apricot kernel extract, capsaicin, and tributyrate. Its core lies in: enhancing overall bioavailability based on the gut health maintained by tributyrate; collectively reducing pancreatic β-cell damage and improving insulin function through the anti-inflammatory and antioxidant effects of mulberry leaf and cactus extracts, the metabolic activation of capsaicin, and the metabolic regulation of apricot kernel extract; and simultaneously synergistically regulating the HPA axis to comprehensively regulate blood glucose and cortisol levels from both metabolic and endocrine dimensions. Attached Figure Description

[0028] Figure 1 The attached figure is for Test Example 2. Detailed Implementation

[0029] To better illustrate the purpose, technical solution, and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0030] The sources of some of the raw materials used in this invention are as follows: Mulberry leaf extract: purchased from Mufan Biotechnology; Cactus extract: purchased from Mufan Biotechnology; Capsaicin: Purchased from Akay Natural Ingredients Private Limited; Tributyric acid glyceride: purchased from NutriScience Innovations LLC; The experimental animals used in this invention are zebrafish, which are raised in fish farming water at 28 ℃ (water quality: 200 mg of instant sea salt added per 1 L of reverse osmosis water, conductivity 450~550 μS / cm; pH 6.5~8.5; hardness 50~100 mg / L CaCO3). They were bred and provided by Hangzhou Baihuan Biotechnology Fish Farming Center. The experimental animal use license number is: SYXK (Zhejiang) 2022-0004. The breeding and management meet the requirements of international AAALAC certification (certification number: 001458).

[0031] The instruments, consumables and reagents used in this invention: Dissecting microscope (SZX7, OLYMPUS, Japan); CCD camera (VertA1, Shanghai Tusen Vision Technology Co., Ltd., China); Motorized focusing continuous zoom fluorescence microscope (AZ100, Nikon, Japan); Precision electronic balance (CP214, OHAUS, USA); High-speed centrifuge (TG16G, Shanghai Yihe Biotechnology Co., Ltd., China); Blood glucose meter (ACCU-CHEKPerforma, Roche Diagnostics Products (Shanghai) Co., Ltd., China); Microinjection device (IM-300, Narishige, Japan); Needle puller (PC-10, Narishige, Japan); Ultrasonic cleaner (JP-010T, Shenzhen Jiemeng Cleaning Equipment Co., Ltd., China); Multifunctional microplate reader (SPARK, TECAN, Austria).

[0032] Streptozotocin (STZ, batch number K1922114, Shanghai Aladdin Biochemical Technology Co., Ltd., China); Pure egg yolk powder (batch number 20230203, Zhejiang Agribusiness Biotechnology Co., Ltd., China); Glucose (batch number I2209335, Shanghai Aladdin Biochemical Technology Co., Ltd., China); Anhydrous ethanol (batch number 20210107, Sinopharm Chemical Reagent Co., Ltd., China); Blood glucose meter test strips (batch number 478829, Roche Diagnostics Products (Shanghai) Co., Ltd., China); Methylcellulose (batch number C2004046, Shanghai Aladdin Biochemical Technology Co., Ltd., China); Zebrafish Cortisol Elisa Kit (catalog number ml312467, batch number 202309, Shanghai Enzyme-Linked Biotechnology Co., Ltd., China).

[0033] All other raw materials, reagents, and equipment were commercially available.

[0034] Preparation of compositions that help maintain healthy blood sugar levels Composition 1 It is composed of mulberry leaf extract, cactus extract, apricot kernel extract, capsaicin, and glyceryl tartrate in a mass ratio of 1:7:6:3:2; Preparation method: Mix the above raw materials evenly, seal and store in a dark place.

[0035] Composition 2 It is composed of mulberry leaf extract, cactus extract, apricot kernel extract, capsaicin, and glyceryl tartrate in a mass ratio of 1:5:5:1:1; The preparation method is the same as that of composition 1.

[0036] Composition 3 It is composed of mulberry leaf extract, cactus extract, apricot kernel extract, capsaicin, and glyceryl tartrate in a mass ratio of 1:10:7:5:5; The preparation method is the same as that of composition 1.

[0037] Composition ① Unlike composition 1, which lacks mulberry leaf extract, composition ① is composed of cactus extract, apricot kernel extract, capsaicin, and glyceryl tartrate in a mass ratio of 7:6:3:2. The preparation method is the same as that of composition 1.

[0038] Composition ② Unlike composition 1, which lacks cactus extract, composition ② consists of mulberry leaf extract, apricot kernel extract, capsaicin, and glyceryl tartrate in a mass ratio of 1:6:3:2. The preparation method is the same as that of composition 1.

[0039] Composition ③ Unlike composition 1, composition 3 lacks Prunus japonica seed extract. Composition 3 consists of mulberry leaf extract, cactus extract, capsaicin, and glyceryl tartrate in a mass ratio of 1:7:3:2. The preparation method is the same as that of composition 1.

[0040] Composition ④ Unlike composition 1, composition 4 lacks capsaicin and consists of mulberry leaf extract, cactus extract, apricot kernel extract, and glyceryl tartrate in a mass ratio of 1:7:6:2. The preparation method is the same as that of composition 1.

[0041] Composition ⑤ Unlike composition 1, composition 5 lacks glyceryl tributyrate and consists of mulberry leaf extract, cactus extract, apricot kernel extract and capsaicin in a mass ratio of 1:7:6:3. The preparation method is the same as that of composition 1.

[0042] Composition ⑥ Composition ⑥ consists of mulberry leaf extract, cactus extract, apricot kernel extract, capsaicin, and glyceryl tartrate in a mass ratio of 1:3:2:7:6; The preparation method is the same as that of composition 1.

[0043] Test Example 1: Glucose Decrease Test See Table 1 for the test samples and concentrations.

[0044] Wild-type AB strain zebrafish with a 3-day pf (dpf) count were randomly selected and placed in beakers, with 30 zebrafish treated in each beaker. Samples were administered via water-soluble administration (concentrations shown in Table 1). A normal control group and a model control group were also included. Each beaker had a volume of 25 mL. Except for the normal control group, all other groups received an injection of 2 nL STZ (200 μg / mL) into the yolk sac. During the day, a 0.15% egg yolk powder solution was administered via water-soluble administration, and at night, a 3% glucose solution was administered via water-soluble administration to establish a diabetic model of pancreatic β-cell apoptosis in zebrafish. After treatment at 28 ℃ for 2 days, the zebrafish were washed three times with standard dilution water. Data were collected using a glucometer, and the glucose levels of the zebrafish were analyzed and statistically evaluated. The intervention effect on glucose levels was evaluated using the statistical analysis results. Statistical results are expressed as mean ± SE. Statistical analysis showed that p < 0.05 was considered statistically significant.

[0045] Table 1 Effect of the composition on glucose levels

[0046] Compared with the model control group, *p < 0.05, **p < 0.01, ***p < 0.001.

[0047] Under the experimental conditions, compositions 1-3 all had the effect of assisting in lowering blood sugar; compositions ①-⑤ and the single-formula raw material group did not have obvious blood sugar lowering effects; composition ⑥ had a certain blood sugar lowering effect, but its effect was far lower than that of composition 1.

[0048] Test Example 2: Protective efficacy of the composition against pancreatic β-cell damage Transgenic zebrafish with 3 dpf pancreatic β-cells and green fluorescent fluorescence were randomly selected and placed in beakers, with 30 zebrafish treated in each beaker. Samples were administered via water-soluble administration (concentrations shown in Table 2). A normal control group and a model control group were also included, with each beaker containing 25 mL. Except for the normal control group, all other groups received 2 nL STZ (200 μg / mL) injected into the yolk sac. During the day, 0.15% egg yolk powder solution was administered via water-soluble administration, and at night, 3% glucose solution was administered via water-soluble administration to establish a diabetic model of pancreatic β-cell apoptosis in zebrafish. After treatment at 28 ℃ for 2 days, 10 zebrafish from each group were randomly selected and photographed under a fluorescence microscope. Images were saved, and data were analyzed and collected using NIS-Elements D 3.20 advanced image processing software. The fluorescence intensity of zebrafish pancreatic β-cells was analyzed and statistically analyzed to evaluate the protective efficacy against pancreatic islet damage (pancreatic β-cell fluorescence intensity). Statistical results are expressed as mean ± SE. Statistical analysis of the results showed that p < 0.05 was statistically significant.

[0049] Table 2. Protective effect of the composition on pancreatic β cells

[0050] Compared with the model control group, *p < 0.05, **p < 0.01, ***p < 0.001.

[0051] Under the experimental conditions, compared with the model control group, the cactus extract and capsaicin in the single-ingredient group had certain protective effects against pancreatic β-cell damage, while the protective effects of combinations 1-3 and combination 6 on pancreatic β-cell damage were extremely significant, specifically manifested by increasing the fluorescence intensity of pancreatic β-cells; however, the mulberry leaf extract, apricot kernel extract and glyceryl tartrate in the single-ingredient group did not have any protective effects against pancreatic β-cell damage, and the protective effects of combinations 1-5 in the formulation group on pancreatic β-cell damage were not obvious.

[0052] Effect of the composition in Test Example 3 on cortisol levels Wild-type AB strain zebrafish with a 3-day pf growth rate (dpf) were randomly selected and placed in beakers, with 30 zebrafish treated in each beaker. Samples were administered via water-soluble solutions (concentrations shown in Table 3). A normal control group and a model control group were also included. Each beaker had a volume of 25 mL. Three biological replicates were performed. Except for the normal control group, all other groups received 2 nL STZ (200 μg / mL) injected into the yolk sac. During the day, 0.15% egg yolk powder solution was administered via water-soluble solution, and at night, 3% glucose solution was administered via water-soluble solution to establish a diabetic model of pancreatic β-cell apoptosis in zebrafish. After treatment at 28 ℃ for 2 days, data were collected using a multi-functional microplate reader according to the instructions of the Zebrafish Cortisol Elisa Kit. The cortisol content in each experimental group of zebrafish was analyzed, and the protective efficacy against pancreatic islet damage (cortisol content) was evaluated based on the statistical analysis results. Statistical results are expressed as mean ± SE. Statistical analysis showed that p < 0.05 was considered statistically significant.

[0053] Table 3 Effect of the composition on cortisol content

[0054] Compared with the model control group, *p < 0.05, **p < 0.01, ***p < 0.001.

[0055] As shown in Table 3, under the experimental conditions, cactus extract and glyceryl tributate in the single-ingredient groups had a certain effect in reducing cortisol levels, while the mulberry leaf extract group, apricot kernel extract, and capsaicin group showed no significant effect in reducing cortisol. Combinations 1-3 in the formulation groups all showed highly significant protective effects against pancreatic islet damage, specifically manifested in a substantial reduction in cortisol levels compared to the control group.

[0056] Comparative test results of Examples 1-3 show that compositions 1-3 significantly reduce blood glucose and cortisol levels and have a certain protective effect on pancreatic β cells. Comparison of compositions 1-3 with the results of single-ingredient groups shows that the combined use of the five ingredients has a significant synergistic effect. Comparison of composition 1 with compositions ①-⑤ shows that the absence of any one of the five ingredients significantly reduces the effects of reducing blood glucose and cortisol levels and protecting pancreatic β cells. Comparison of composition 1 with composition ⑥ shows that using the ingredient ratios within the scope defined by this invention results in better effects of reducing blood glucose and cortisol levels and protecting pancreatic β cells.

[0057] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A composition that helps maintain healthy blood sugar levels, characterized in that, It includes mulberry leaf extract, cactus extract, apricot kernel extract, capsaicin, and glyceryl tartrate in a mass ratio of 1:5-10:5-7:1-5:1-5.

2. The composition according to claim 1, characterized in that, The mass ratio of mulberry leaf extract, cactus extract, apricot kernel extract, capsaicin, and glyceryl tartrate is 1:7:6:3:

2.

3. The use of the composition as described in claim 1 or 2 in the preparation of health products that help maintain healthy blood sugar levels.

4. The application as described in claim 3, characterized in that, The health product dosage form is any one of powder, ointment, pill, tablet, capsule, or oral liquid.

5. A capsule that helps maintain healthy blood sugar levels, characterized in that, The capsule comprises the composition of claim 1 or 2 that helps maintain healthy blood sugar levels.

6. The capsule as described in claim 5, characterized in that, The capsules also contain excipients acceptable for health supplements.

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