Use of fokienia hodginsii ethanol extract in preparation of blood sugar lowering drugs

Abstract

The application discloses application of Fokienia hodginsii ethanol extract in preparation of blood sugar reducing drugs. The Fokienia hodginsii ethanol extract is prepared from Fokienia hodginsii leaves as raw materials through 75% ethanol soaking extraction and low-temperature drying. In a type 2 diabetes mouse model induced by high fructose and high fat feed, the result of oral starch tolerance experiment shows that the extract can dose-dependently significantly reduce postprandial blood sugar, and the mechanism is related to inhibition of starch digestion pathway. The application provides a basis for application of the Fokienia hodginsii extract in preparation of blood sugar reducing drugs, prevention or treatment of diabetes functional products.

Description

Technical Field

[0001] This invention relates to novel pharmaceutical uses of plant extracts, specifically the application of an ethanol extract of the leaves of *Fokienia hodginsii* in the preparation of a drug for lowering postprandial blood glucose, belonging to the field of natural product chemistry and pharmacology. Background Technology

[0002] Diabetes mellitus is a chronic metabolic disease caused by defects in insulin secretion and / or utilization due to multiple etiologies, characterized primarily by hyperglycemia. Of these, 90%–95% are type 2 diabetes. Overall hyperglycemia is closely related to postprandial hyperglycemia and is considered a significant risk factor for the occurrence, development, and complications of diabetes. Existing synthetic drugs have limitations, including limited glycemic control efficacy, significant side effects, and high treatment costs. Therefore, developing highly effective, inexpensive, and low-toxicity plant-derived natural drugs for lowering blood sugar and preventing or treating diabetes is of significant clinical importance.

[0003] Fujian cypress (Cupressus hominis) is an evergreen tree belonging to the genus *Cupressus* in the family Cupressaceae. It is distributed in Fujian, Jiangxi, Sichuan, Guizhou, southern Zhejiang, southern Hunan, northern Guangdong, and southeastern Yunnan provinces of my country. Traditional records indicate its effects in regulating qi, relieving pain, and suppressing nausea and vomiting. Modern research shows that its main components include diterpenoids, sesquiterpenoids, phenylpropanes, and flavonoids, but its pharmacological activities in lowering blood sugar and preventing or treating diabetes have not yet been reported. Summary of the Invention

[0004] The purpose of this invention is to provide a new pharmaceutical use for the ethanol extract of *Platycladus orientalis*, namely, its application in the preparation of drugs that lower postprandial blood glucose.

[0005] To achieve the above objectives, the technical solution provided by the present invention is as follows: The application of the ethanol extract of *Platycladus orientalis* leaves in the preparation of drugs for lowering postprandial blood glucose. The hypoglycemic, preventative, or therapeutic effects on diabetes are based on a unique mechanism of inhibiting the starch digestion pathway.

[0006] In one embodiment, the preparation method of the Fujian cypress leaf ethanol extract is as follows: Fresh Fujian cypress leaves are taken, washed, and air-dried at room temperature. After being chopped, they are added to a 75% (v / mL) ethanol aqueous solution at a material-to-liquid ratio of 1:10 (g / mL). The mixture is then soaked and extracted in a sealed container at room temperature for 3 days. After extraction, the soaking liquid is collected and dried under reduced pressure or normal pressure at 42℃ until constant weight is obtained, yielding a brownish-yellow to brownish-brown extract. This extract should be sealed, protected from light, and stored in a dry place.

[0007] The pharmacodynamic experiments were conducted using a type 2 diabetic mouse model induced by a high-fructose, high-fat diet. The hypoglycemic activity and mechanism of the extract were studied by comparing the results of oral starch tolerance test and oral glucose tolerance test.

[0008] The experimental results showed that in the oral starch tolerance test, compared with the model control group, the ethanol extract of *Platycladus orientalis* leaves significantly reduced the area under the postprandial blood glucose curve in a dose-dependent manner. The differences were statistically significant at extract doses of 0.8 g / kg, 1.0 g / kg, and 3.0 g / kg (p<0.05), and it significantly inhibited the rise in blood glucose at 60, 90, and 120 minutes after gavage. Notably, in the oral glucose tolerance test, the area under the postprandial blood glucose curve in the same dose range of the extract intervention group did not show statistically significant differences compared with the model control group.

[0009] The results of the comparative experiments above indicate that the hypoglycemic and diabetes prevention or treatment effects of this extract are only observed when carbohydrates are ingested in the form of starch, and have no significant effect on the body's ability to directly process monosaccharides (glucose). This strongly demonstrates that the mechanism of action of the ethanol extract of *Platycladus orientalis* leaves in lowering postprandial blood glucose is not through promoting insulin secretion or improving insulin resistance, but specifically through inhibiting the digestive enzyme pathway of starch in the small intestine.

[0010] Based on the above-described mechanism of action, the drug dosage form of the present invention is preferably an oral formulation. In one specific embodiment, the oral formulation is a solution, prepared by dispersing a therapeutically effective amount of ethanol extract of *Platycladus orientalis* in a vegetable oil. The vegetable oil is preferably olive oil, which not only serves as a safe excipient but may also have the benefit of aiding in metabolic improvement.

[0011] The application provided by this invention offers a novel drug option with a natural plant-derived mechanism of action for postprandial blood glucose management in type 2 diabetes, particularly suitable for patients whose diet consists mainly of carbohydrates. The extract is simple to prepare, inexpensive, and shows promising development potential. Attached Figure Description

[0012] Figure 1 Figure 1 shows the experimental results of this invention. In the figure, A is the blood glucose curve of each group in OST; B is the area under the curve (AUC) of OST; C is the blood glucose curve of each group in OGTT; and D is the area under the curve (AUC) of OGTT. Detailed Implementation

[0013] The technical solution of the present invention will be further described in detail below with reference to specific embodiments and accompanying drawings. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

[0014] Example 1: Fresh, disease-free leaves of *Platycladus orientalis* were collected, washed with running water to remove surface dust, and air-dried at room temperature. The leaves were then cut into small pieces approximately 0.5-1.0 cm². 100 g of the chopped leaves were accurately weighed and placed in a suitable container. 1000 mL of a 75% (v / v) ethanol aqueous solution was added, stirred thoroughly, and sealed. The container was then soaked at room temperature in the dark for 3 days. After soaking, the extract was filtered through four layers of gauze and collected. The solvent was concentrated under reduced pressure using a rotary evaporator at 42°C, and then vacuum-dried at the same temperature to constant weight to obtain the dried ethanol extract of *Platycladus orientalis* leaves. The extract was then sealed in a brown desiccator and stored in the dark for later use.

[0015] Example 2: A type 2 diabetes model was established using 6-week-old SPF-grade male ICR mice fed a high-fructose, high-fat diet for 8 consecutive weeks. Fasting blood glucose was measured via tail vein after 10 hours of fasting, and mice with a fasting blood glucose ≥7.0 mmol / L were designated as successful model mice. The successful model mice were randomly divided into 5 groups according to body weight and fasting blood glucose: a model control group (olive oil), a positive control group (acarbose 10 mg / kg for the OSTTT test; metformin 125 mg / kg for the OGTT test), and high, medium, and low dose groups of Fujian cypress extract (doses of 3.0 g / kg, 1.0 g / kg, and 0.8 g / kg, respectively, all prepared with olive oil as the solvent). The gavage volume for each group was 0.1 mL / 10g body weight.

[0016] In the OSTTT experiment, each group received 3 g / kg corn starch suspension via gavage along with the corresponding intervention; in the OGTT experiment, each group received 4 g / kg glucose solution via gavage along with the corresponding intervention. Blood samples were collected from the tail vein at specified time points, and blood glucose levels were measured using a glucometer. The area under the curve (AUC) was used as the evaluation index for the overall postprandial blood glucose exposure level. One-way ANOVA was used for inter-group comparisons, and p < 0.05 was considered statistically significant.

[0017] The results confirmed that, in the OSTTT model, compared with the model control group, the postprandial blood glucose AUC and blood glucose values ​​at multiple time points in all groups treated with Fujian cypress extract were significantly reduced in a dose-dependent manner (p<0.05), while in the OGTT model, there was no statistically significant difference in AUC among the groups. These results clearly indicate that its hypoglycemic mechanism lies in inhibiting starch digestion, rather than affecting glucose metabolism itself.

[0018] In conclusion, the extract of *Platycladus orientalis* significantly reduced postprandial blood glucose only when starch was administered simultaneously, indicating that its hypoglycemic effect is related to the inhibition of starch digestion pathway.

Claims

1. Application of ethanol extract of *Platycladus orientalis* in the preparation of hypoglycemic drugs and in the prevention or treatment of diabetes.

2. The application of the ethanol extract of *Platycladus orientalis* according to claim 1 in the preparation of hypoglycemic drugs, characterized in that, The Fujian cypress ethanol extract is an ethanol extract of Fujian cypress leaves.

3. The application of the Fujian cypress ethanol extract according to claim 2 in the preparation of hypoglycemic drugs, characterized in that, The Fujian cypress ethanol extract is prepared by the following method: fresh Fujian cypress leaves are washed, dried, and chopped, then soaked in 75% ethanol at a ratio of 1:

10. After soaking for 3 days, the soaking liquid is collected and dried at 42°C to obtain the extract.

4. The application of the ethanol extract of *Platycladus orientalis* according to claim 1 in the preparation of hypoglycemic drugs, characterized in that, The hypoglycemic, diabetes prevention or treatment drugs work by inhibiting the starch digestion pathway.

5. The application of the ethanol extract of *Platycladus orientalis* according to claim 5 in the preparation of hypoglycemic drugs, characterized in that, The blood sugar lowering, diabetes prevention or treatment drugs mentioned are oral preparations.

6. The application of the ethanol extract of *Platycladus orientalis* according to claim 6 in the preparation of hypoglycemic drugs, characterized in that, The oral preparation is a solution, which is made by dispersing an ethanol extract of Fujian cypress in vegetable oil.

7. The application of the ethanol extract of *Platycladus orientalis* according to claim 7 in the preparation of hypoglycemic drugs, characterized in that, The vegetable oil is olive oil.

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