Para-hydroxybenzaldehyde a and its use

Abstract

The present application relates to p-hydroxybenzaldehyde A and its application. The p-hydroxybenzaldehyde A has the following structural formula. The present application takes the acron as the raw material, adopts the ethanol immersion, the organic solvent extraction, the chromatography, the high performance liquid chromatography and the like method to prepare the p-hydroxybenzaldehyde A. And further research finds that the compound has the effect of reducing blood sugar and treating diabetes cognitive impairment, social obstacle, 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-hydroxybenzaldehyde 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-hydroxybenzaldehyde 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-hydroxybenzaldehyde compound, named p-hydroxybenzaldehyde 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-hydroxybenzaldehyde A for the first time. Further research shows that this compound has a good effect on the treatment of diabetes. p-hydroxybenzaldehyde 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-hydroxybenzaldehyde A.

[0010] The p-hydroxybenzaldehyde 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 field.

[0011] This invention provides a method for preparing p-hydroxybenzaldehyde A, comprising the following steps: preparing p-hydroxybenzaldehyde A using succulent fruit as a 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-hydroxybenzaldehyde 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 45:55.

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

[0020] This invention provides the application of the above-mentioned p-hydroxybenzaldehyde 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-hydroxybenzaldehyde A in the preparation of drugs that lower blood sugar.

[0022] The present invention provides the use of the above-mentioned p-hydroxybenzaldehyde A in the preparation of medicaments for the treatment and / or prevention of cognitive impairment, preferably, it can be used for the treatment and / or prevention of diabetic cognitive impairment.

[0023] The present invention provides the use of the above-mentioned p-hydroxybenzaldehyde 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-hydroxybenzaldehyde A and preparations containing p-hydroxybenzaldehyde 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-Hydroxybenzaldehyde A 1 H NMR spectrum (horizontal axis scale from 10 to 0 from left to right);

[0030] Figure 2 p-Hydroxybenzaldehyde A 13 C NMR spectrum (horizontal axis scale from 200 to 0 from left to right);

[0031] Figure 3 HSQC spectrum of p-hydroxybenzaldehyde A (horizontal axis scale from left to right: 11 to -0.5; vertical axis scale from bottom to top: 200 to -10);

[0032] Figure 4 HMBC spectrum of p-hydroxybenzaldehyde A (horizontal axis scale from left to right: 10 to -1; vertical axis scale from bottom to top: 200 to -20);

[0033] Figure 5 HR-ESI-MS spectrum of p-hydroxybenzaldehyde 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-hydroxybenzaldehyde compound was obtained, and the chemical structure, pharmacological activity and uses of the compound were further clarified.

[0037] p-Hydroxybenzaldehyde 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-hydroxybenzaldehyde A is shown in formula (I).

[0039]

[0040] The preparation method of p-hydroxybenzaldehyde 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-hydroxybenzaldehyde A described in this invention.

[0045] Research has shown that the p-hydroxybenzaldehyde 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-hydroxybenzaldehyde 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 (45:55, volume ratio) as the solvent to finally obtain the compound p-hydroxybenzaldehyde A described in this invention.

[0054] p-Hydroxybenzaldehyde 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 hydroxybenzaldehyde A was further analyzed.

[0056] p-Hydroxybenzaldehyde 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-Hydroxybenzaldehyde 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 429.1201. - The peak indicates that the molecular formula is C. 22 H 22 O9. 1 In the H-NMR (400MHz, DMSO-d6) spectrum, δ H The values ​​of 7.81 (2H, d, J = 8.8 Hz) and 7.19 (2H, d, J = 8.8 Hz) suggest the presence of a para-substituted benzene ring structure in the structure; simultaneously, δ H The values ​​of 7.52 (2H, d) and 6.78 (2H, d, J = 8.5 Hz) suggest that the structure also contains a para-substituted benzene ring. H The integral area of ​​hydrogen at position 7.51 is 3, combined with δ H The hydrogen signal at 6.37 (1H, d, J = 16.0 Hz) suggests the presence of a trans-double bond and a hydrogen signal related to δ. H The para-substituted hydrogen signals at position 7.51 overlap, thus forming a structural segment consisting of a p-hydroxycinnamic acid core and a para-substituted benzene ring, while δ H The typical terminal carbon signal of the sugar at 5.13 (1H, d, J = 7.2 Hz) and the high-field signal reveal that the para-substituted benzene ring and the p-hydroxycinnamic acid are linked by a sugar molecule. δ H :4.42(1H,m) and δ H:4.18 (1H, dd, J = 11.9, 7.0 Hz) represents the two hydrogen signals on the methylene group at the 6' position, while δ H: 3.77(1H,m) is the hydrogen signal at the fifth position.

[0062] 13 There are 18 carbon signals in C-NMR (100MHz, DMSO-d6), among which δ C The high carbon signals at 131.48, 130.27, 116.36, and 115.83, combined with chemical shift and proton NMR characteristics, confirm the existence of two para-substituted benzene ring structures in the structure. The three carbon signals above 160 are presumed to be ester bond carbon signals in p-hydroxycinnamic acid and two carbon signals on the benzene ring directly bonded to oxygen; one is bonded to the end group of the sugar, and the other is presumed to be bonded to a hydroxyl group, further verifying the core structure of p-hydroxycinnamic acid. Meanwhile, the δ... C The signals at 144.84 and 113.75 confirm the existence of the trans double bond, further proving the existence of the p-hydroxycinnamic acid core; δ C The carbon signal of 99.36 and the values ​​of 76.27, 73.88, 73.01, 69.88, and 63.20 confirm the presence of sugar in the structure. One side of the para-substituted benzene ring is replaced by a sugar terminal group, while the other side is bound to a δ-terminal group. C: The signal of 191.17 suggests the presence of an aldehyde group.

[0063] Further analysis using HSQC spectra reveals that δ C: 63.20 and δ H: 4.18 and 4.42 are related, and are attributed to the methylene carbon at the 6' position, δ C: 73.88 and δ H: The 3.77 correlation proves it to be a 5' carbon signal, while δ C: 69.88 and δ H: 3.23 related, δ C 76.27, 73.01 and δ H The correlation between 3.33 and 3.30 proves the corresponding order of glucose ring-related signals. And δ C: Both 130.27 and 144.84 are related to δ H: The peak correlation at 7.52 also proves δ H: The hydrogen signal at position 7.52 is due to the overlap between the hydrogen signal (H7”) on the double bond and the hydrogen signal on the benzene ring.

[0064] Combined with HMBC spectrum, δ C: 99.36 and δ H: 3.30 related, prove δ C: 73.01 is the carbon at position 2'; δ C: 73.88 and δH: 4.18 Related, prove δ C: 73.88 is the carbon at position 5'; δ C: 73.01 and δ H: 3.23 is related, and the δ can be seen from the QC spectrum. H: δ is at position 3.23. C: 69.88, therefore δ C: If 69.88 belongs to C3', then C4' is δ. C: 76.27. δ C: 130.45 and δ H: 9.78 correlation, proving that the chemical shift value at position 1 is δ C 130.45; δ C: 191.17 and δ H: If 7.81 is relevant, then it proves δ H: 7.81 represents a 2-bit and a 6-bit hydrogen signal; while δ C: 131.48 represents the 2-bit and 6-bit carbon signal, because δ C: 124.74 and δ H: The hydrogen signal at 6.37 is correlated, indicating it is a 1-bit signal; δ H: 6.78 is also related to the carbon signal, indicating that it is the hydrogen signal at 3”, 5”, hence δ H: 7.19 represents the 3rd and 5th bit hydrogen signals, establishing the connection sequence.

[0065] HSQC and HMBC spectra provide information on all direct hydrogen-carbon bonds in the structure, as shown in equation (II):

[0066]

[0067] The configuration of the compound was further determined by a sugar hydrolysis experiment. The determination method included the following steps: 4 mg of sample was taken, 2 mol / L hydrochloric acid was prepared, 5 mL of the solution was taken, and the mixture was heated under reflux in an oil bath at 100 °C for 2 h (with magnetic stirring). After complete hydrolysis, the mixture was extracted three times with dichloroisocyanuric acid. The lower layer solution was discarded, and the aqueous layer was continuously added to the solution and distilled under reduced pressure until neutral to obtain the sample.

[0068] The peaks were compared with those of the sugar standard in a polarimetric liquid chromatography system, and the experimental results are as follows: Figures 6A to 6C As shown. 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 This is a diagram showing the sugar hydrolysis of p-hydroxybenzaldehyde A. Because... Figure 6B and 6C The consistent peak direction indicates that the compound is a β-D-glucoside.

[0069] In summary, based on the results of high-resolution mass spectrometry, nuclear magnetic resonance spectroscopy, and sugar hydrolysis experiments, p-hydroxybenzaldehyde A belongs to the p-hydroxybenzaldehyde class of compounds and can be named 6'-O-hydroxycinnamic acid-p-hydroxybenzaldehyde-4-O-β-D-glucopyranoside.

[0070] Example 2 Determination of the hypoglycemic effect of p-hydroxybenzaldehyde A

[0071] Seventy male Wistar rats, weighing 240 ± 20 g, 10 - 12 weeks old, of 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 body weight. Among them, 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 a high-sugar and high-fat diet for 4 weeks. After 4 weeks, they were intraperitoneally injected with a freshly prepared 1% streptozotocin (STZ) sodium citrate suspension (40 mg·kg -1 ). The rats in the blank control group were continuously fed a normal diet for 4 weeks. After 4 weeks, they were intraperitoneally injected with an equal volume of normal saline. During this period, the two groups of rats drank water normally. The rats were tail-bled to detect their fasting blood glucose level (FBG). Rats with blood glucose concentrations greater than 11.1 mmol / L for three consecutive days were regarded as successfully modeled diabetic rats.

[0072] The preparation method of the 1% streptozotocin (STZ) STZ sodium citrate suspension includes the following steps: Citric acid (A): 2.10 g of citric acid was dissolved in 100 ml of distilled water; Sodium citrate (B): 2.94 g of sodium citrate was dissolved in 100 ml of distilled water; Solution A and solution B were mixed in a volume ratio of 1:1.32, the pH value was measured, and the pH value was adjusted to 4.2 - 4.5. It was filtered and sterilized with a microporous membrane (Φ = 0.22 μm) and stored in a 4°C refrigerator for later use. The STZ powder was made into a 1% solution with the above buffer solution, prepared immediately before use, protected from light and ice-bathed, and injected immediately after dissolution, and the injection was completed within 10 minutes.

[0073] The successfully modeled diabetic rats were divided into a positive drug group, a high-dose p-hydroxybenzaldehyde A administration group (referred to as the high-dose group), a medium-dose p-hydroxybenzaldehyde A administration group (referred to as the medium-dose group), a low-dose p-hydroxybenzaldehyde A administration group (referred to as the low-dose group), and a model group.

[0074] Each group was gavaged once a day. When gavaging, p-hydroxybenzaldehyde A was dissolved in water for gavage.

[0075] Positive drug group: Metformin (15 μmol·kg) -1 ) administered by gavage; the high-dose group was given p-hydroxybenzaldehyde A (dose 800 mg·kg) -1 The concentration was 80 mg / mL. The medium-dose group was given p-hydroxybenzaldehyde A (dose 400 mg·kg). -1 The high-dose group received p-hydroxybenzaldehyde A (concentration 40 mg / mL) via gavage; the low-dose group received p-hydroxybenzaldehyde 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.

[0076] 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.

[0077] As shown in Table 2, after administration of p-hydroxybenzaldehyde A to rats, compared with the model group, the high-dose group showed a significant decrease in blood glucose levels, while the medium-dose and low-dose groups showed some improvement in blood glucose levels. The rats also experienced an increase in body weight and relief of symptoms such as polyuria, polydipsia, and polyphagia. This indicates that p-hydroxybenzaldehyde A can improve the symptoms of diabetes in rats and has a blood glucose-lowering effect.

[0078] Table 2 Effects of p-hydroxybenzaldehyde A on blood glucose levels in diabetic rats

[0079]

[0080] Compared with the control group * P<0.05, ** P<0.01; compared with the model group # P<0.05.

[0081] Example 3: Treatment of Diabetic Cognitive Impairment

[0082] The water maze test was used to determine the intervention effect of p-hydroxybenzaldehyde A on cognitive impairment in diabetic rats.

[0083] 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-hydroxybenzaldehyde 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.

[0084] 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.

[0085] 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 positive drug group rats crossed platforms and the time spent active around the platforms were significantly increased (P<0.05), indicating that the model group rats with diabetes had cognitive impairment, and administration of p-hydroxybenzaldehyde A can treat the cognitive impairment in diabetic rats to a certain extent.

[0086] Table 3. Effects of p-hydroxybenzaldehyde A on swimming speed in diabetic rats

[0087]

[0088] Compared with the control group * P<0.05, ** P<0.01; compared with the model group # P<0.05.

[0089] Table 4. Effects of p-hydroxybenzaldehyde A on the latency period of diabetic rats.

[0090]

[0091] Compared with the control group * P<0.05, ** P<0.01; compared with the model group # P<0.05.

[0092] Table 5. Effects of p-hydroxybenzaldehyde A on spatial exploration in diabetic rats (mean ± SD)

[0093]

[0094] Compared with the control group * P<0.05, ** P<0.01; compared with the model group # P<0.05.

[0095] Example 4: Determination of the intervention effect of p-hydroxybenzaldehyde A on social impairment in diabetic rats.

[0096] 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-hydroxybenzaldehyde 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.

[0097] 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.

[0098] 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 in the cage. This indicates that the diabetic rats in the model group exhibited social behavioral impairment, and that administration of p-hydroxybenzaldehyde A can, to some extent, treat this impairment.

[0099] Table 6. Effects of p-hydroxybenzaldehyde A on social behavior disorders in diabetic rats.

[0100]

[0101] Compared with the control group * P<0.05, ** P<0.01; compared with the model group # P<0.05.

[0102] 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-Hydroxybenzaldehyde A, characterized in that, It has the following structural formula:

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

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

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

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

6. The use of p-hydroxybenzaldehyde 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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