P-hydroxyphenethyl alcohol a and its use

Abstract

The present application relates to p-hydroxyphenethyl alcohol A and its application. The p-hydroxyphenethyl alcohol A has the following structural formula. The present application takes the acron as raw material, adopts ethanol extraction, organic solvent extraction, chromatography, high performance liquid chromatography and other methods to prepare p-hydroxyphenethyl alcohol A. And further research finds that the compound has the effects of reducing blood sugar and treating diabetes cognitive impairment and social impairment, and can be used for treating diabetes.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and particularly relates to p-hydroxyphenylethanol A and its applications. Background Technology

[0002] Fructus Embeliae, the mature, dried fruit of *Embelia oblongifolia* Hemsl., a plant belonging to the Myrsinaceae family, is mainly distributed in Yunnan, Guangxi, Jiangxi, Fujian, and Guizhou provinces. It is believed to have blood-tonifying and hemostatic effects. In addition to containing certain nutrients, the peel and pulp of Fructus Embeliae also contain anthocyanins, which are highly safe as a coloring agent in processed foods and have considerable development and utilization value.

[0003] Currently, domestic and international researchers mainly focus their studies on the chemical composition of the fruit of the Sour Vine Fruit on its roots and leaves, while there is relatively little research on the chemical composition of its fruit, and related content is also scarce. Summary of the Invention

[0004] In view of the problems existing in the prior art, the present invention provides p-hydroxyphenylethanol A and its applications.

[0005] The technical solution of the present invention to solve the above-mentioned technical problems is as follows:

[0006] This invention provides a p-hydroxyphenylethanol compound, named p-hydroxyphenylethanol A, having the following structural formula:

[0007]

[0008] The beneficial effects of this invention: This invention uses the fruit of the sour vine as raw material to prepare p-hydroxyphenylethanol A for the first time. Further research shows that this compound has a good effect on the treatment of diabetes. p-hydroxyphenylethanol A can lower blood sugar and treat cognitive impairment and social impairment in diabetes.

[0009] The present invention provides a formulation comprising the above-mentioned p-hydroxyphenylethanol A.

[0010] The p-hydroxyphenylethanol A provided by this invention can be widely used in pharmaceuticals, food, health products, and other fields, without special limitations on the dosage form. For example, to meet the needs of treatment or prevention, it can be prepared into a pharmaceutical formulation according to certain dosage form requirements. Other ingredients can be added during the preparation process according to conventional methods in the art.

[0011] The present invention provides a method for preparing p-hydroxyphenylethanol A, comprising the following steps: preparing p-hydroxyphenylethanol A using succulent fruit as raw material.

[0012] Specifically, it includes the following steps:

[0013] (1) The total ethanol extract of the fruit of the vine was dispersed in water and then extracted with petroleum ether, dichloromethane and ethyl acetate in sequence to obtain an ethyl acetate extract.

[0014] (2) The ethyl acetate extract was treated with silica gel column chromatography and eluted with a dichloromethane-methanol gradient.

[0015] (3) A volume ratio of dichloromethane to methanol of 100:7 was selected to elute the fraction, which was then separated by ODS column chromatography with methanol-water gradient elution.

[0016] (4) The fraction prepared by methanol and water in a volume ratio of 60:40 was separated by high performance liquid chromatography and isocratic elution was performed using methanol-water (containing 0.1% formic acid) as the mobile phase.

[0017] The inventors tried different methods in their research and found that the above method was beneficial for the successful preparation of p-hydroxyphenylethanol A.

[0018] Preferably, in step (1), the volume ratio of petroleum ether, dichloromethane, and ethyl acetate can be 1:1:1. In step (3), the ODS undergoes pretreatment. The pretreatment method for the ODS includes: soaking in methanol for 24 hours, loading onto a column, washing with methanol until no turbidity is observed when dropped into water, and then equilibrating with methanol and water as the initial mobile phase, with a methanol to water volume ratio of 5:95. In step (4), the methanol-water mixture has a methanol to water volume ratio of 39:61.

[0019] Adopting the above ratio is beneficial for the successful preparation of p-hydroxyphenylethanol A, and can further improve the yield and purity of p-hydroxyphenylethanol A.

[0020] This invention provides the application of the above-mentioned p-hydroxyphenylethanol A in the preparation of drugs for treating and / or preventing diabetes, which can improve symptoms such as polyuria, polydipsia, and polyphagia.

[0021] This invention provides the application of the above-mentioned p-hydroxyphenylethanol A in the preparation of drugs that lower blood sugar.

[0022] The present invention provides the use of the above-mentioned p-hydroxyphenylethanol A in the preparation of a medicament for treating and / or preventing cognitive impairment, preferably, it can be used for treating and / or preventing diabetic cognitive impairment.

[0023] The present invention provides the use of the above-mentioned p-hydroxyphenylethanol A in the preparation of medicaments for treating and / or preventing social disorders, preferably, for treating and / or preventing social disorders caused by diabetes.

[0024] This invention provides the use of the above-mentioned preparation in the preparation of drugs for the treatment and / or prevention of diabetes, which can improve symptoms such as polyuria, polydipsia, and polyphagia.

[0025] This invention provides the use of the above-mentioned formulation in the preparation of drugs for lowering blood sugar.

[0026] The present invention provides the use of the above-described formulation in the preparation of a medicament for the treatment and / or prevention of cognitive impairment, preferably for the treatment and / or prevention of diabetic cognitive impairment.

[0027] The present invention provides the use of the above-described formulation in the preparation of a medicament for the treatment and / or prevention of social disorders, preferably for the treatment and / or prevention of social disorders caused by diabetes.

[0028] Studies have shown that the p-hydroxyphenylethanol A and preparations containing p-hydroxyphenylethanol A provided by this invention have therapeutic and / or preventive effects on diabetes, and can lower blood sugar and treat and / or prevent cognitive impairment and social impairment in diabetes. Attached Figure Description

[0029] Figure 1 p-Hydroxyphenylethanol A 1 H NMR spectrum (horizontal axis scale from 8 to 0 from left to right);

[0030] Figure 2 p-Hydroxyphenylethanol A 13 C NMR spectrum (horizontal axis scale from 170 to 0 from left to right);

[0031] Figure 3 HSQC spectrum of p-hydroxyphenylethanol A (horizontal axis scale from left to right: 8 to -0.5; vertical axis scale from bottom to top: 180 to 30);

[0032] Figure 4 HMBC spectrum of p-hydroxyphenylethanol A (horizontal axis scale from left to right: 9 to -0.5; vertical axis scale from bottom to top: 180 to 20);

[0033] Figure 5 HR-ESI-MS spectrum of p-hydroxyphenylethanol A;

[0034] Figures 6A to 6C The results of the sugar hydrolysis experiment are as follows, Figure 6A This is a diagram showing the glycolysis of α-L-glucose. Figure 6B This is a diagram showing the glycolysis of β-D-glucose. Figure 6C The image shows the sugar hydrolysis diagram of the sample. Detailed Implementation

[0035] The principles and features of the present invention are described below with reference to the accompanying drawings. The examples given are only for explaining the present invention and are not intended to limit the scope of the present invention.

[0036] In order to make full use of the fruit of the sour vine, this invention takes the mature and dried fruit of the sour vine as the research object and conducts a systematic study on its chemical composition. Unexpectedly, a new p-hydroxyphenylethanol compound was obtained, and the chemical structure, pharmacological activity and uses of the compound were further clarified.

[0037] p-Hydroxyphenylethanol A can be used in the preparation of drugs to lower blood sugar and treat cognitive and social impairments in diabetes, and is used to treat diabetes.

[0038] The structural formula of p-hydroxyphenylethanol A is shown in formula (I).

[0039]

[0040] The preparation method of p-hydroxyphenylethanol A includes the following steps:

[0041] (1) Extraction: The mature, dried fruit of *Embeliae fructus* (family Myrsinaceae) is produced in Yunnan Province. The dried fruit was extracted by heating with 95% industrial alcohol under reflux. The extracts were combined and concentrated under reduced pressure to obtain a total ethanol extract. This total ethanol extract was uniformly dispersed in distilled water and extracted sequentially with petroleum ether, dichloromethane, and ethyl acetate to obtain an ethyl acetate extract.

[0042] (2) Separation: The ethyl acetate extract obtained in step (1) was loaded onto a silica gel column and eluted with a dichloromethane-methanol gradient (dichloromethane to methanol volume ratio of 100:0 to 100:100). The 100:7 fraction (i.e. the fraction obtained by elution with a dichloromethane to methanol volume ratio of 100:7) showed strong dark spots under UV 254nm detection and blue spots under 5% sulfuric acid.

[0043] The obtained product was then separated by pretreated ODS column (Octadecylsilyl, octadecylsilane bonded silica gel packing material) chromatography, eluted with methanol-water gradient to obtain several elution fractions, which were detected by thin-layer chromatography and colorimetrically developed. Each colored elution fraction was concentrated to dryness under reduced pressure to obtain concentrates for later use.

[0044] The obtained fraction was separated by HPLC (high performance liquid chromatography) and isocratic elution was performed using methanol-0.1% formic acid aqueous solution as the mobile phase to finally obtain the compound p-hydroxyphenylethanol A described in this invention.

[0045] Research has shown that the p-hydroxyphenylethanol A provided by this invention can be used in the preparation of drugs for lowering blood sugar and treating cognitive and social impairments in diabetes.

[0046] In this invention, unless otherwise specified, reagents and experimental materials are all conventional reagents and experimental materials in the art, which can be obtained commercially or prepared using conventional methods in the art. Unless otherwise specified, the experimental methods used in this invention are all conventional experimental methods in the art.

[0047] The ODS column model is YMC-Pack ODS-A (5μm, 250×4.6mm).

[0048] The following is a description through specific embodiments.

[0049] Example 1: Extraction and separation of p-hydroxyphenylethanol A

[0050] A total of 30 kg of dried fruit of the *Solanum tuberosum* was extracted three times by heating and reflux with 95% industrial alcohol for 2 hours each time. The extracts were combined and concentrated under reduced pressure to obtain a total ethanol extract. The total ethanol extract was then uniformly dispersed in distilled water and extracted sequentially with petroleum ether, dichloromethane, and ethyl acetate to obtain 80 g of ethyl acetate extract.

[0051] 80g of ethyl acetate extract was loaded onto a silica gel column and eluted using a dichloromethane-methanol gradient (dichloromethane to methanol volume ratio of 100:0 to 100:100). Detection revealed that the 100:7 fraction (i.e., the fraction obtained by elution with a dichloromethane to methanol volume ratio of 100:7) showed strong dark spots under UV 254nm detection and blue spots under 5% sulfuric acid.

[0052] The obtained product (i.e., the 100:7 fraction) was then subjected to pretreated ODS column chromatography (octadecylsilyl, octadecylsilane-bonded silica gel packing material) for separation. Elution was performed using a methanol-water gradient (methanol to water volume ratio of 5:100 to 100:0), yielding several eluent fractions of 5:95, 10:90, 20:80, 30:70, 60:40, 90:10, and 100:0. These fractions were detected by thin-layer chromatography and colorimetric analysis. The 30:70, 60:40, and 90:10 colored eluent fractions were concentrated to dryness under reduced pressure to obtain concentrated fractions (i.e., the distillate) for later use. In the above method, the ODS pretreatment process included: soaking in methanol for 24 hours, loading onto the column, washing with methanol until no turbidity was observed when added to water, and then equilibrating with an initial mobile phase of methanol to water at a ratio of 5:95 (volume ratio).

[0053] The obtained 60:40 fraction was separated by HPLC (high performance liquid chromatography). Isocratic elution was performed using methanol-water (containing 0.1% formic acid) as the mobile phase and methanol and water (39:61, volume ratio) as the solvent to finally obtain the compound p-hydroxyphenylethanol A described in this invention.

[0054] p-Hydroxyphenylethanol A is a brown oily solid (after being dissolved in methanol). It has dark spots under UV light at 254 nm and turns grayish dark spots when it comes into contact with a 10% sulfuric acid ethanol solution (i.e., the volume of sulfuric acid is 10% of the volume of ethanol).

[0055] The structure of hydroxyphenylethanol A was further elucidated.

[0056] p-Hydroxyphenylethanol A 1 H-NMR and 13 C-NMR data are shown in Table 1.

[0057] Table 1 1 H and 13 C NMR data

[0058]

[0059]

[0060] p-Hydroxyphenylethanol A 1 H NMR, 13 1C NMR, 2D-NMR (HSQC, HMBC) spectra and HR-ESI-MS spectra, such as Figures 1 to 5 As shown.

[0061] HR-ESI-TOFMS yielded the [MH] of the compound at m / z 461.1506. - The peak indicates that the molecular formula is C. 23 H 26 O 10 . 1 In the H-NMR (400MHz, DMSO-d6) spectrum, δ H The values ​​of 7.47 (1H, d, J = 15.9 Hz) and 6.25 (1H, d, J = 15.9 Hz) prove the existence of the trans double bond; δ H The integral area at 7.06 is 3, combined with δ H The values ​​of 6.99 (1H, dd, J = 8.1, 1.5 Hz) and 6.77 (1H, d, J = 8.1 Hz) suggest the existence of a 1,2,4-substituted benzene ring structure; while δ H The hydrogen signal with an integral area of ​​3 at 7.06 is determined by δ. H 6.92 (2H, d, J = 8.6 Hz) Predicted δ H The hydrogen signal at position 7.06 is due to the overlap between the hydrogen signal at the para-substituted benzene ring and the hydrogen signal at the 2” position. (δ) H 4.84 (1H, d, J = 7.3Hz) is a typical glycosidic hydrogen signal; while δ HThe carbon spectral data at 3.50 (2H,t,J=7.1Hz) and 2.59 (2H,t,J=7.1Hz) suggest the presence of two linked methylene groups in the structure. Based on their relatively large chemical shift values, it is speculated that they are linked to a benzene ring or a hydroxyl group.

[0062] 13 The C-NMR (100MHz, DMSO-d6) data incorporates our analyzed proton NMR data, and is analyzed via δ¹⁸O₂. C 129.58 (C-2, C-6) and 116.00 (C-3, C-5) determined the structure of the para-substituted benzene ring; while δ C The values ​​of 121.33 (C-6”), 115.74 (C-2”), and 114.72 (C-5”) confirm the existence of the ABX coupling system, combined with the trans double bond and δ C 166.30 (C-9”) proves the existence of the caffeic acid structure and suggests that it is linked to the pyranose ring; δ C 63.33 (C-8) and 38.11 (C-7) indicate that a methylene C-7 is attached to the para-substituted benzene ring, followed by a -CH2OH, which corresponds to the data in the proton NMR spectrum.

[0063] To further determine the linkage order and confirm whether the two methylene groups are attached to the pyranose ring or in the para position, HSQC spectra were analyzed: δ C 38.11 and δ H 2.59 correlation, δ C 63.33 and δ H 3.50 correlation, representing two directly linked methylene signals; δ C 70.00 and δ H 3.22 Related, δ C 73.15 and δ H 3.25 related, δ C 76.39 and δ H 3.28 is related to the signal at the 2', 3', and 4' positions on the glucose molecule; the specific connection order needs to be determined in conjunction with the BC spectrum; δ C 73.72 and δ H 3.64 correlation, representing the signal at the 5' position of the sugar; δ C 63.33 and δ H Correlation between 4.16 and 4.43 suggests a 6' bit signal; δ C 100.44 and δ H 4.84 correlation, attributed to carbon signals at the end group; in the low field region, δ C 113.67 and 145.21 are respectively related to δ HRelated to 6.25 and 7.47, which are signals on the trans double bond. The connection positions of the two methylene groups were determined by the HMBC spectrum: δ C The oxygenated benzene ring carbon signal at δ 155.52 is correlated with the anomeric hydrogen signal of the sugar at δ H 4.84, indicating that the 1'-position is directly connected to the 4-position of the benzene ring, and the methylene groups at the 7- and 8-positions should be connected to the 1-position, as shown in formula (II).

[0064]

[0065] Furthermore, the configuration of glucose was determined by sugar hydrolysis experiment. Take 5 mg of p-hydroxyphenylethyl alcohol A, prepare 2 mol / L hydrochloric acid, take 5 mL, heat and reflux in an oil bath at 100 °C for 2 h (magnetic stirring). After complete hydrolysis, extract three times with dichloromethane, discard the lower layer solution, and continuously add water to the aqueous layer and distill under reduced pressure to neutrality to obtain the sample.

[0066] The peak elution was compared with the sugar standard on an optical rotation liquid phase, and the results are as Figures 6A to 6C shown. Figure 6A It is the sugar hydrolysis diagram of α-L-glucose,[[]] Figure 6B It is the sugar hydrolysis diagram of β-D-glucose,[[]] Figure 6C It is the sugar hydrolysis diagram of p-hydroxyphenylethyl alcohol A. Because Figure 6B and 6C have the same peak elution direction, it can be judged that this compound is β-D-glucoside.

[0067] In summary, based on the high-resolution mass spectrometry combined with nuclear magnetic resonance spectroscopy and the results of sugar hydrolysis experiment, p-hydroxyphenylethyl alcohol A belongs to the p-hydroxyphenylethyl alcohol compounds, and it can be named 6'-O-caffeoyl-p - -hydroxyphenylethyl alcohol-4-O-β-D-glucopyranoside (6'-O-caffeoyl-p-hydroxyphenylethyl alcohol-4-O-β-D-glucopyranoside).

[0068] Example 2 Determination of the hypoglycemic effect of p-hydroxyphenylethyl alcohol A

[0069] 70 male Wistar rats, weighing 240 ± 20 g, 10 - 12 weeks old, SPF grade, were purchased from Changchun Yisi Experimental Animal Technology Co., Ltd., license number: SCXK(Ji)-2018-0007. The rats were randomly divided into a blank control group (referred to as the blank group) and a diabetes model group according to their body weights. There were 10 rats in the blank control group and 60 rats in the diabetes model group. The rats in the model group were continuously fed with a high-sugar and high-fat diet for 4 weeks. After 4 weeks, they were intraperitoneally injected with freshly prepared 1% streptozotocin (STZ) sodium citrate suspension (40 mg·kg -1The blank control group rats were fed a normal diet for 4 consecutive weeks, and then injected intraperitoneally with an equal volume of physiological saline. Both groups of rats had normal drinking water intake during this period. Fasting blood glucose (FBG) levels were measured by tail amputation. Rats with a blood glucose concentration greater than 11.1 mmol / L for three consecutive days were considered successfully modeled diabetic rats.

[0070] The preparation method of 1% streptozotocin (STZ) and sodium citrate suspension includes the following steps: Citric acid (A): 2.10g citric acid dissolved in 100ml distilled water; Sodium citrate (B): 2.94g sodium citrate dissolved in 100ml distilled water; Mix solutions A and B at a volume ratio of 1:1.32, measure the pH value, adjust the pH value to 4.2-4.5, filter through a microporous membrane (Φ=0.22μm) for sterilization, and store at 4℃ for later use. Prepare a 1% solution of STZ powder using the above buffer solution, prepare fresh each time, keep in the dark and on an ice bath, and inject immediately after dissolution, completing the injection within 10 minutes.

[0071] The successfully modeled diabetic rats were divided into a positive drug group, a high-dose p-hydroxyphenylethanol A group (referred to as the high-dose group), a medium-dose p-hydroxyphenylethanol A group (referred to as the medium-dose group), a low-dose p-hydroxyphenylethanol A group (referred to as the low-dose group), and a model group.

[0072] All groups received gavage once daily. During gavage, p-hydroxyphenylethanol A was dissolved in water and administered via gavage.

[0073] Positive drug group: Metformin (15 μmol·kg) -1 ) administered by gavage; the high-dose group was given p-hydroxyphenylethanol A (dose 800 mg·kg) -1 The concentration was 80 mg / mL. The medium-dose group was given p-hydroxyphenylethanol A (dose 400 mg·kg). -1 The high-dose group received p-hydroxyphenylethanol A (concentration 40 mg / mL) via gavage; the low-dose group received p-hydroxyphenylethanol A (dose 200 mg / kg). -1 The drug (at a concentration of 20 mg / mL) was administered by gavage; the blank control group and the model group were administered physiological saline by gavage. The drugs were administered continuously for 4 weeks, once daily, with fasting blood glucose (FBG) measured every other week using a blood glucose meter. The results are shown in Table 2.

[0074] Before administration, comparison showed that the mental state and hair luster of the rats in the blank control group were better than those in the diabetic model group, and the rats in the diabetic model group showed typical symptoms of diabetes such as polyuria, polydipsia, weight loss and polyphagia.

[0075] As shown in Table 2, after administration of p-hydroxyphenylethanol A to rats, compared with the model group, the blood glucose level in the high-dose group was significantly reduced, and the blood glucose levels in the medium-dose and low-dose groups were improved. The rats' body weight increased, and the symptoms of polyuria, polydipsia, and polyphagia were alleviated. This indicates that p-hydroxyphenylethanol A can improve the symptoms of diabetes in rats and has a blood glucose-lowering effect.

[0076] Table 2. Effects of p-hydroxyphenylethanol A on blood glucose levels in diabetic rats

[0077]

[0078] Compared with the control group * P<0.05, ** P<0.01; compared with the model group # P<0.05.

[0079] Example 3: Treatment of Diabetic Cognitive Impairment

[0080] The water maze test was used to determine the intervention effect of p-hydroxyphenylethanol A on cognitive impairment in diabetic rats.

[0081] Eighty Wistar rats were randomly divided into a control group and a model group. The model group was induced into diabetes according to the method described in Example 2. After successful modeling, the model group was randomly divided into three groups of 20 rats each: a positive control group, a treatment group, and a model group. The positive control group received donepezil (2 mg / kg) once daily via gavage. -1 ); Treatment group: p-hydroxyphenylethanol A (800 mg / kg) was administered by gavage once daily. -1 ·d -1 (Concentration of 80 mg / mL); the blank group and the model group were given physiological saline by gavage twice a day.

[0082] On day 60 after modeling, the Morris water maze experiment was conducted. One day prior to the formal experiment, all rats swam freely for 2 minutes in a water maze without platforms or markers to acclimatize to the aquatic environment and avoid stress. The Morris water maze was a circular pool with a diameter of 150 cm and a height of 50 cm, divided into four quadrants by four equidistant points. Different markers—colored cards of triangles, squares, circles, and pentagrams—were affixed to the center of the pool walls in each quadrant. A platform was placed in the center of one quadrant, 2 cm below the water surface, and the water temperature was controlled at (23.0±2.0)℃. The rats underwent the Morris water maze navigation experiment. During the experiment, rats were randomly placed into the water facing the pool walls in three quadrants other than the target quadrant (the quadrant containing the platform). The escape latency was recorded as an indicator of learning performance. After locating the platform, the rats were allowed to remain on it for 10 seconds; the latency period was the time it took for the rat to find the platform. If the rat did not find the platform within 90 seconds, the latency period was recorded as 90 seconds, and the rat was guided onto the platform and remained there for 10 seconds, allowing it to learn and memorize spatial information based on the four quadrants of the reference points. After each training session, the rats were removed and dried to prevent stress caused by hypothermia. Measurements were taken twice daily for each rat for 5 consecutive days. After the orientation and navigation experiment, the platform was removed, and each rat was randomly placed into the water; the number of times the rat traversed the platform within 90 seconds was recorded.

[0083] The experimental results are shown in Tables 3 to 5. In the water maze experiment, the average swimming speed of the model group rats was not statistically different from that of the control group (P>0.05), thus eliminating the interference of swimming speed on the escape latency. Compared with the blank control group, the escape latency of the model group rats was significantly prolonged (P<0.01); compared with the model group, the escape latency of the positive drug group and the drug administration group was significantly shortened (P<0.05). In the spatial exploration experiment, compared with the blank control group, the average swimming speed of the model group rats was not statistically different (P>0.05), but the number of times the model group rats crossed platforms and the time spent active around the platforms were significantly reduced (P<0.05); compared with the model group, the average swimming speed of the positive drug group and the drug administration group was not statistically different (P>0.05), but the number of times the model group rats crossed platforms was significantly increased (P<0.05), and the time spent active around the platforms was significantly prolonged (P<0.05). This indicates that the model group rats with diabetes have cognitive impairment, and administration of p-hydroxyphenylethanol A can treat the cognitive impairment in diabetic rats to a certain extent.

[0084] Table 3. Effects of p-hydroxyphenylethanol A on swimming speed in diabetic rats

[0085]

[0086] Compared with the control group * P<0.05, **P<0.01; compared with the model group # P<0.05.

[0087] Table 4. Effects of p-hydroxyphenylethanol A on the latency period of diabetic rats.

[0088]

[0089] Compared with the control group * P<0.05, ** P<0.01; compared with the model group # P<0.05.

[0090] Table 5. Effects of p-hydroxyphenylethanol A on spatial exploration in diabetic rats (mean ± SD)

[0091]

[0092] Compared with the control group * P<0.05, ** P<0.01; compared with the model group # P<0.05.

[0093] Example 4: Determination of the intervention effect of p-hydroxyphenylethanol A on social impairment in diabetic rats.

[0094] Eighty Wistar rats were randomly divided into a control group and a model group. The model group was induced into diabetes according to the method described in Example 2. After successful modeling, the model group was randomly divided into three groups of 20 rats each: a positive control group, a treatment group, and a model group. The positive control group received donepezil (2 mg / kg) once daily via gavage. -1 ); Treatment group: p-hydroxyphenylethanol A (800 mg / kg) was administered by gavage once daily. -1 ·d -1 (Concentration of 80 mg / mL); the blank group and the model group were given physiological saline by gavage twice a day.

[0095] On the 60th day after modeling, a social interaction behavior experiment was conducted. Before the experiment, the rats were placed in a social behavior box. After they became familiar with the environment, their social ability was judged by the time and number of times they approached the metal cage of another rat from the same batch in the social behavior box within 5 minutes.

[0096] The experimental results are shown in Table 6. The social interaction behavior experiment revealed that the time and frequency of contact between rats and the metal cage were significantly higher in the control group than in the model group. Furthermore, compared to the drug-treated group and the positive control group, the drug-treated group and the positive control group showed higher contact times and frequencies between rats and the cage. This indicates that the model rats with diabetes exhibited social behavioral impairment, and that administration of p-hydroxyphenylethanol A can, to some extent, treat the social behavioral impairment in diabetic rats.

[0097] Table 6. Effects of p-hydroxyphenylethanol A on social behavior disorders in diabetic rats.

[0098]

[0099] Compared with the control group * P<0.05, ** P<0.01; compared with the model group # P<0.05.

[0100] The above description is only a preferred embodiment of the present invention and is not intended to limit 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.

Claims

1. p-Hydroxyphenylethanol A, characterized in that, It has the following structural formula:

2. A formulation, characterized in that, Includes p-hydroxyphenylethanol A as described in claim 1.

3. The use of p-hydroxyphenylethanol A according to claim 1 in the preparation of a medicament for treating and / or preventing diabetes.

4. The use of p-hydroxyphenylethanol A according to claim 1 in the preparation of a drug for lowering blood sugar.

5. The use of p-hydroxyphenylethanol A according to claim 1 in the preparation of medicaments for the treatment and / or prevention of cognitive impairment.

6. The use of p-hydroxyphenylethanol A according to claim 1 in the preparation of a medicament for treating and / or preventing social disorders.

7. The use of the formulation of claim 2 in the preparation of a medicament for treating and / or preventing diabetes.

8. The use of the formulation of claim 2 in the preparation of a drug for lowering blood sugar.

9. The use of the formulation of claim 2 in the preparation of a medicament for treating and / or preventing cognitive impairment.

10. Use of the formulation of claim 2 in the preparation of a medicament for treating and / or preventing social disorders.

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