A B-ring cleaved flavone, its preparation method and uses

Abstract

The present invention discloses a B-ring seco-flavonoid, a preparation method and uses thereof; the B-ring seco-flavonoid is isolated from the bark of Cinnamomum cassia; its structural formula is as shown in formula (I) and / or formula (II):; The present invention is isolated from the dry bark of Cinnamomum cassia, a plant of the genus Cinnamomum in the Lauraceae family, and the hepatoprotective activity is evaluated using an alcohol-induced hepatocyte injury model. It is found that the B-ring seco-flavonoid of the present invention can effectively alleviate alcohol-induced damage to normal hepatocytes in mice and reduce fat accumulation, indicating that the B-ring seco-flavonoid provided by the present invention has hepatoprotective activity and can be applied in the preparation of hepatoprotective drugs, and has good research and development prospects.

Description

Technical Field

[0001] The present invention belongs to the field of natural medicine chemistry, and particularly relates to a B-ring cleaved flavone compound, a preparation method thereof, and uses thereof. Background Art

[0002] Alcoholic liver disease is a liver disease caused by long-term excessive alcohol consumption. Clinically, the disease spectrum of alcoholic liver disease is mainly divided into: alcoholic fatty liver, alcoholic hepatitis, alcoholic liver fibrosis, and alcoholic cirrhosis. Severe alcoholism can induce extensive hepatocyte necrosis and even cause liver failure. According to the "Guidelines for the Prevention and Treatment of Alcoholic Liver Disease in China", having a long-term history of alcohol consumption (generally more than 5 years), with the ethanol equivalent being ≥ 40 g / day for men and ≥ 20 g / day for women; or having a history of heavy alcohol consumption within two weeks, with the ethanol equivalent being greater than 80 g / day, is considered excessive alcohol consumption and there is a relatively high risk of developing alcoholic liver disease.

[0003] The clinical treatment methods for alcoholic liver disease mainly include alcohol abstinence, nutritional support, drug treatment, and liver transplantation. Alcohol abstinence and nutritional support are the most basic treatment measures. Complete alcohol abstinence can enable some patients with mild alcoholic liver disease to return to normal, delay the fibrosis process, and improve the survival rate of patients. However, patients are prone to poor compliance and the improvement effect is not obvious. Moreover, sudden alcohol withdrawal may cause severe withdrawal reactions such as epilepsy, coma, and even cardiac arrest in patients with alcohol dependence. For patients who have difficulty in voluntarily abstaining from alcohol, aldehyde dehydrogenase inhibitors (such as disulfiram), central nervous system inhibitors (such as the opioid receptor antagonist naltrexone, the gamma-aminobutyric acid receptor agonist baclofen), and liver protectants (such as the trace element zinc) can be given to improve the clinical biochemical indexes of patients with alcoholic liver disease. For patients with alcohol withdrawal syndrome, sedative drugs (such as benzodiazepines) can be used. Patients with alcoholic liver disease also require good nutritional support. On the basis of alcohol abstinence, the daily diet should pay attention to high protein, low fat, and timely supplementation of vitamins and folic acid, etc.

[0004] In terms of drug treatment, based on the accumulation of long-term evidence-based medical evidence, silymarin preparations have been listed as liver-protecting drugs in multiple liver disease diagnosis and treatment guidelines. Silymarin can reduce the level of CYP2E1 in hepatocytes of patients with alcoholic liver disease, inhibit the production of ROS, MDA, etc., regulate glutathione metabolism, and also reduce the levels of inflammatory factors such as IL-6 and TNF-α, improving the symptoms of alcoholic liver disease. However, the treatment mechanism of silymarin is not yet clear, and the drug has poor oral bioavailability and a large pharmacodynamic dose. Liver-protecting drugs such as bicyclol, glycyrrhizin preparations, S-adenosylmethionine, and N-acetylcysteine also have a similar effect of improving relevant pathological indicators in patients with alcoholic liver disease. Metadoxine, on the one hand, as an antioxidant, improves the oxidative stress response of hepatocytes; on the other hand, it can accelerate the clearance of alcohol in the body and has a good effect on patients with acute alcohol poisoning. Although there are various palliative therapies for the drug treatment of alcoholic liver disease, they can only improve symptoms, and the relevant treatment mechanisms have not been clarified, and even easily cause adverse reactions such as infection, hepatotoxicity, and hepatorenal syndrome. Generally speaking, most of the existing drugs for the treatment of alcoholic liver disease in clinical practice play an auxiliary treatment role, and the curative effect is limited. Therefore, it is imperative to find effective and safe drugs for anti-alcoholic liver disease.

[0005] Cinnamon (Cinnamomum cassia Presl.) is a medium-sized arbor plant of the genus Cinnamomum in the Lauraceae family. Also known as Jun Gui, Du Gui, Da Gui, Tong Gui, etc., it is widely distributed in the tropical and subtropical regions of East Asia and Southeast Asia. It is a traditional Chinese medicine with both medicinal and edible uses, and has the effects of tonifying fire and assisting yang, guiding fire back to the origin, dispelling cold and relieving pain, and warming and dredging the meridians. B-ring fission flavone compounds are a rare type of plant component and have been less studied currently. The present invention is to discover and isolate a class of B-ring fission flavone compounds from the dry bark of cinnamon, and it has been experimentally proven that they have liver-protecting activity. Summary of the Invention

[0006] The first object of the present invention is to provide a class of B-ring fission flavones;

[0007] The B-ring fission flavones provided by the present invention are isolated from cinnamon bark, and their structural formulas are shown as formula (I) or / and formula (II):

[0008] 。

[0009] The present invention discovers through experiments that the B-ring fission flavones of the present invention have good liver-protecting activity and can be used to prepare liver-protecting drugs.

[0010] Therefore, the second object of the present invention is to provide the application of the above-mentioned B-ring fission flavones in the preparation of liver-protecting drugs.

[0011] The above B-ring fission flavone was isolated from the dry bark of Cinnamomum cassia, a plant of the genus Cinnamomum in the Lauraceae family. The dry Cinnamomum cassia medicinal material was purchased from Qingping Traditional Chinese Medicine Market, Liwan District, Guangzhou City, Guangdong Province in April 2021. The sample was stored in the School of Biotechnology and Pharmaceutical Sciences, Guangdong University of Technology (No.: CC-202104, Location: School of Biotechnology and Pharmaceutical Sciences, Guangdong University of Technology, 100 West Outer Ring Road, Guangzhou Higher Education Mega Center, Guangzhou, China, 510006).

[0012] The preparation method of the above B-ring fission flavone specifically includes the following steps:

[0013] (1) Take the dry bark of Cinnamomum cassia and extract it by heating under reflux with 60% ethanol aqueous solution twice, 2 hours each time. After filtration, the filtrate is concentrated under reduced pressure to obtain a concentrated solution;

[0014] (2) The concentrated solution is extracted with dichloromethane to obtain a dichloromethane extract;

[0015] (3) Perform normal pressure silica gel column chromatography on the obtained dichloromethane extract. Specifically, gradient elution is carried out successively with eluents of cyclohexane-ethyl acetate with volume ratios of 99:1, 97:3, 95:5, 90:10, 85:15, 80:20, 70:30, 60:40, and 0:100 to obtain a total of 17 sub-fractions C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, and C17;

[0016] (4) Subject the sub-fraction C10 eluted with cyclohexane-ethyl acetate with a volume ratio of 80:20 to medium and low pressure reverse phase column chromatography, and elute successively with methanol-water-formic acid with volume ratios of 35:65:0.1, 40:60:0.1, 45:55:0.1, 50:50:0.1, 60:40:0.1, 70:30:0.1, 80:20:0.1, 100:0:0 to obtain a total of 23 sub-fractions C10.1, C10.2, C10.3, C10.4, C10.5, C10.6, C10.7, C10.8, C10.9, C10.10, C10.11, C10.12, C10.13, C10.14, C10.15, C10.16, C10.17, C10.18, C10.19, C10.20, C10.21, C10.22, and C10.23;

[0017] (5) Subject the sub-fraction C10.9 eluted with methanol-water-formic acid with a volume ratio of 45:55:0.1 to preparative reverse phase high performance liquid chromatography, and elute with acetonitrile-water-formic acid with a volume ratio of 32:68:0.1 at a flow rate of 10 mL / min to obtain the compound of formula (Ⅱ);

[0018] (6) The sub-fractions C15 and C16 eluted with cyclohexane-ethyl acetate in a volume ratio of 60:40 were combined and passed through a medium and low pressure reverse phase column chromatography, and eluted successively with methanol-water-formic acid in volume ratios of 25:75:0.1, 30:70:0.1, 35:65:0.1, 40:60:0.1, 45:55:0.1, 50:50:0.1, 55:45:0.1, 60:40:0.1, 65:35:0.1, 70:30:0.1, 80:20:0.1, 100:0:0 to obtain 20 sub-fractions: C15&16.1, C15&16.2, C15&16.3, C15&16.4, C15&16.5, C15&16.6, C15&16.7, C15&16.8, C15&16.9, C15&16.10, C15&16.11, C15&16.12, C15&16.13, C15&16.14, C15&16.15, C15&16.16, C15&16.17, C15&16.18, C15&16.19 and C15&16.20;

[0019] (7) The sub-fraction C15&16.9 eluted with methanol-water-formic acid in a volume ratio of 45:55:0.1 was prepared by reverse phase preparative high performance liquid chromatography, and eluted with methanol-water-formic acid in a volume ratio of 45:55:0.1 at a flow rate of 8 mL / min to obtain the compound of formula (I).

[0020] Another technical solution of the present invention is the application of the above B-ring cleaved flavone in the preparation of hepatoprotective drugs.

[0021] Another technical solution of the present invention is a hepatoprotective drug with B-ring cleaved flavone as the active ingredient.

[0022] Compared with the prior art, the technical solution provided by the present invention has the following technical advantages:

[0023] The technical solution provided by the present invention isolated 2 flavonoid compounds from the bark of Cinnamomum cassia, a plant of the genus Cinnamomum in the Lauraceae family, and evaluated the hepatoprotective activity using an alcohol-induced hepatocyte injury model. It was found that the B-ring cleaved flavone compound of the present invention can effectively alleviate alcohol-induced damage to normal hepatocytes in mice and reduce fat accumulation, indicating that the B-ring cleaved flavone compound provided by the present invention has hepatoprotective activity and can be applied in the preparation of hepatoprotective drugs, and has good research and development prospects. Brief Description of the Drawings

[0024] Figure 1 is the 400 MHz 1H NMR spectrum of the compound of formula (I) in deuterated dimethyl sulfoxide;

[0025] Figure 2It is the 100 MHz carbon nuclear magnetic resonance spectrum of the compound of formula I in deuterated dimethyl sulfoxide;

[0026] Figure 3 It is the 600 MHz proton nuclear magnetic resonance spectrum of the compound of formula II in deuterated methanol;

[0027] Figure 4 It is the 150 MHz carbon nuclear magnetic resonance spectrum of the compound of formula II in deuterated methanol;

[0028] Figure 5 It is the detection chart of the hepatoprotective activity of the B-ring cleaved flavone compound. Specific Embodiments

[0029] The present invention will be further described below in conjunction with specific embodiments, but the implementation manners of the present invention are not limited thereto.

[0030] All the equipment in the following examples is as follows:

[0031] The mass spectrometer is the Bruker amazon SL mass spectrometer produced by Bruker Daltonics, USA. The superconducting nuclear magnetic resonance spectrometers are Bruker AV-400 and Bruker AV-600. The X-ray single crystal diffractometer is Bruker D8 venture. The silica gel GF254 for thin layer chromatography and the column chromatography silica gel (200 - 300 mesh) are all products of Qingdao Ocean Chemical Factory. The reversed-phase ODS packing (50 μ m) is a product of YMC Company, Japan. The medium and low pressure liquid chromatograph is a product of Shanghai LISUI Electronic Technology Co., Ltd. The preparative chromatographic column used for liquid phase separation is Cosmosil Packed C18 column (20.0 × 250 mm, 5 μ m). The acetonitrile or methanol used for liquid chromatography is chromatographically pure, the water is double distilled water, and other reagents are all analytically pure. The multi-functional microplate reader is the Infinite F50 microplate reader of Tecan Company, Switzerland. Normal mouse liver cells are purchased from the Cell Bank of the Chinese Academy of Sciences. Silymarin is a product of Shanghai Aladdin Company.

[0032] Example 1 Preparation of Compounds of Formula (I) - Formula (II)

[0033] 20.0 kg of dried cinnamon bark is refluxed and extracted with 200 L of ethanol-water (60:40, v / v) twice, each time for 2 hours. After filtration, the filtrate is concentrated under reduced pressure to obtain a concentrated solution. The concentrated solution is successively extracted with 39 L of dichloromethane to obtain the dichloromethane extract.

[0034] 434.3 g of dichloromethane extract was subjected to normal pressure silica gel column chromatography, and gradient elution was carried out successively with cyclohexane-ethyl acetate eluents with volume ratios of 99:1, 97:3, 95:5, 90:10, 85:15, 80:20, 70:30, 60:40, and 0:100 to obtain a total of 17 sub-fractions, namely C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, and C17 (see Table 1 for the corresponding sub-fractions eluted with cyclohexane-ethyl acetate of different volume ratios).

[0035] Then, the sub-fraction C10 (8.2 g) eluted with cyclohexane-ethyl acetate with a volume ratio of 80:20 was subjected to medium and low pressure reverse phase column chromatography, and elution was carried out successively with methanol-water-formic acid with volume ratios of 35:65:0.1, 40:60:0.1, 45:55:0.1, 50:50:0.1, 60:40:0.1, 70:30:0.1, 80:20:0.1, and 100:0:0 to obtain a total of 23 sub-fractions, namely C10.1, C10.2, C10.3, C10.4, C10.5, C10.6, C10.7, C10.8, C10.9, C10.10, C10.11, C10.12, C10.13, C10.14, C10.15, C10.16, C10.17, C10.18, C10.19, C10.20, C10.21, C10.22, and C10.23 (see Table 2 for the corresponding fractions eluted with methanol-water-formic acid of different volume ratios).

[0036] The sub-fraction C10.9 (114.3 mg) eluted with methanol-water-formic acid with a volume ratio of 45:55:0.1 was prepared by reverse phase preparative high performance liquid chromatography, and elution was carried out using acetonitrile-water-formic acid with a volume ratio of 32:68:0.1 at a flow rate of 10 mL / min to obtain the compound of formula (II) t R : 83.4 min, 9.8 mg, purity 95%);

[0037]

[0038] Similarly, the sub-fractions C15 and C16 eluted with cyclohexane-ethyl acetate in a volume ratio of 60:40 (15.4 g) were combined and passed through a medium and low pressure reverse phase column chromatography, and eluted successively with methanol-water-formic acid in volume ratios of 25:75:0.1, 30:70:0.1, 35:65:0.1, 40:60:0.1, 45:55:0.1, 50:50:0.1, 55:45:0.1, 60:40:0.1, 65:35:0.1, 70:30:0.1, 80:20:0.1, 100:0:0 to obtain 20 sub-fractions C15&16.1, C15&16.2, C15&16.3, C15&16.4, C15&16.5, C15&16.6, C15&16.7, C15&16.8, C15&16.9, C15&16.10, C15&16.11, C15&16.12, C15&16.13, C15&16.14, C15&16.15, C15&16.16, C15&16.17, C15&16.18, C15&16.19 and C15&16.20 (see Table 3 for the fractions corresponding to cyclohexane-ethyl acetate elution with different volume ratios).

[0039] The sub-fraction C15&16.9 (149.1 mg) eluted with methanol-water-formic acid in a volume ratio of 45:55:0.1 was prepared by reverse phase preparative high performance liquid chromatography. The preparative conditions of the high performance liquid chromatography were as follows: elution was carried out with methanol-water-formic acid in a volume ratio of 45:55:0.1 at a flow rate of 8 mL / min to obtain the compound of formula (I) ( t R : 39.5 min, 13.9 mg, purity 95%).

[0040]

[0041] The physical and chemical constants are as follows:

[0042] Compound of formula (I): white needle-like crystals; m.p. 158.1−160.0 °C; α 25 D +21.7 ( c 0.1, methanol); UV (methanol) λ max (log ε ) 218 (4.34), 270 (3.26) nm; IR (KBr) v max 3449,2934, 2841, 1775, 1624, 1596, 1501, 1152, 1050 cm -1; ESIMS (positive ion) m / z 351.2 [M + H] + ; HRESIMS (positive ion) m / z 351.1076 [M + H] + (Calculated value for C 17 H 19 O8] + , 351.1074), the molecular formula of the compound was determined to be C 17 H 18 O8; The reference for the 1H NMR spectrum Figure 1 , the reference for the 13C NMR spectrum is shown in Figure 2, and the data are listed in Table 4; The single crystal diffraction data of the compound of formula (I) are shown in Table 5

[0043] Compound of formula (II): White amorphous powder; α 25 D +22.5 ( c 0.1, methanol); UV (methanol) λ max (log ε ) 208 (3.91), 233 (3.18) nm; ECD ( c 1.60 ×10 −3 M, methanol) λ max (Δ ε ) 208(4.56); IR (KBr) v max 3449, 2936, 2842, 1778, 1622, 1595, 1503, 1147, 1057 cm -1 ; ESIMS (positive ion) m / z 307.1 [M + H] + ; HRESIMS (positive ion) m / z 329.0996 [M + Na] + (Calculated value for C 16 H 18 O6Na] + , 329.0996), the molecular formula of the compound was determined to be C 16 H 18 O6; The reference for the 1H NMR spectrum Figure 3 , the reference for the 13C NMR spectrum is shown in Figure 4, and the data are listed in Table 4

[0044] Table 1 Association table of sub-fractions obtained with cyclohexane-ethyl acetate eluent at the same volume ratio

[0045]

[0046] Table 2 Correlation Table of Sub-fractions Obtained with Methanol-Water-Formic Acid Eluents with Different Volume Ratios

[0047]

[0048] Table 3 Correlation Table of Sub-fractions Obtained with Cyclohexane-Ethyl Acetate Eluents with Different Volume Ratios

[0049]

[0050] Table 4 Carbon NMR and Proton NMR Data of Compounds of Formula (I) and Formula (II) and Their Assignments

[0051]

[0052] a The test solvent was deuterated dimethyl sulfoxide (proton NMR frequency 400 MHz, carbon NMR frequency 100 MHz).

[0053] b The test solvent was deuterated methanol (proton NMR frequency 600 MHz, carbon NMR frequency 150 MHz).

[0054] Table 5 Single Crystal Diffraction Data of Compound of Formula (I)

[0055]

[0056] Analysis of Hepatoprotective Activity of B-Ring Cleaved Flavone Compounds in Example 2

[0057] The following shows the in vitro hepatoprotective activities of B-ring cleaved flavone compounds of formula (I) and formula (II) and the positive control drug silymarin disclosed in this patent.

[0058] The specific method is as follows:

[0059] Establishment of alcoholic hepatocyte injury model: Mouse normal hepatocytes were seeded at 1×10 μ in 96-well plates (100 μ μL / well) and 24-well plates (500 4 and 5×10 4Plate the cells according to the density, and incubate them adherently for 24 hours. Aspirate the culture medium in the wells. For the treatment group, add a DMEM / F-12 culture medium containing 10 μmol / L of the monomer to be tested (the monomer to be tested is a B-ring cleaved flavone compound with the structural formula shown in Formula (Ⅰ) or a B-ring cleaved flavone compound with the structural formula shown in Formula (Ⅱ)) or 10 μmol / L of the positive control drug silymarin and 1000 mmol / L of absolute ethanol; for the model group, add a DMEM / F-12 culture medium containing 1000 mmol / L of absolute ethanol, and for the blank group, add a blank culture medium, and continue to culture for 24 hours. The cell viability was detected by CCK-8 assay for 96-well plates, and qualitative photography and quantitative detection were performed by Oil Red O staining for 24-well plates.

[0060] Cell viability detection: After culturing the cells in the 96-well plates for 24 hours with modeling and drug administration, aspirate the culture medium in the wells, add a DMEM / F-12 culture medium containing 10% CCK-8 reagent, and incubate in the cell culture incubator at 37°C in the dark for 2.5 hours. Subsequently, use a microplate reader to detect the absorbance values of the above treatment group and blank group at a wavelength of 450 nm. Calculate the cell viability (%) through the formula: cell viability (%) = [A (treatment group) - A (blank group)] × 100%.

[0061] Preparation of Oil Red O stock solution: Weigh 150 mg of Oil Red O solid in the dark, add 25 mL of isopropanol, and dissolve it by ultrasonic treatment.

[0062] Preparation of Oil Red O working solution: In the dark, mix the Oil Red O stock solution and ultrapure water at a ratio of 3:2, and filter it through a 0.22 μ μm microporous filter membrane.

[0063] Cell Oil Red O staining and detection: After culturing the cells in the 24-well plates for 24 hours with modeling and drug administration, aspirate the culture medium in the wells, and wash each well with 500 μ μL of phosphate buffered saline twice. Then add 4% paraformaldehyde and fix it at room temperature in the dark for 30 minutes, rinse it twice with 60% isopropanol, add the Oil Red O working solution and stain it in the dark for 30 minutes, wash the 24-well plates with phosphate buffered saline, and then take pictures under an inverted microscope. Finally, add 250 μ μL of isopropanol to each well and shake gently. Pipette 200 μ μL from each well and transfer it to a 96-well plate, and measure the absorbance value at 492 nm with a microplate reader.

[0064] The results are as Figure 5 shown. From Figure 5 A (cell viability after the B-ring cleaved flavone compound acts on alcohol-induced normal mouse hepatocytes for 24 h), Figure 5 B (Oil Red O quantification after the B-ring cleaved flavone compound acts on alcohol-induced normal mouse hepatocytes for 24 h) in Figure 5C (the ratio of Oil Red O quantification to cell viability of mouse normal hepatocytes induced by alcohol after 24 h treatment with B-ring seco-flavonoid compounds), Figure 5 As can be seen from D (Oil Red O staining pictures of mouse normal hepatocytes induced by alcohol after 24 h treatment with B-ring seco-flavonoid compounds) in Figure 5 , the two B-ring seco-flavonoid compounds of the present invention can significantly alleviate the damage of mouse normal hepatocytes induced by alcohol, reduce fat accumulation, and have good hepatoprotective activity. Therefore, the two B-ring seco-flavonoid compounds of the present invention can be used in the preparation of hepatoprotective drugs.

[0065] The two B-ring seco-flavonoid compounds prepared in this application can significantly alleviate the damage of mouse normal hepatocytes induced by alcohol, reduce fat accumulation, and have good hepatoprotective activity. Therefore, the two B-ring seco-flavonoid compounds of the present invention can be used in the preparation of hepatoprotective drugs.

[0066] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. A method for preparing a compound of formula (II), characterized in that, The structural formula of the compound of formula (II) is as follows: ; Specifically, it includes the following steps: (1) Take the dried bark of cinnamon and extract it by heating under reflux with 60% ethanol aqueous solution twice, 2 hours each time. After filtration, the filtrate is concentrated under reduced pressure to obtain a concentrated solution; (2) Extract the concentrated solution with dichloromethane and collect the extract; (3) Perform normal pressure silica gel column chromatography on the extract, and elute it successively with cyclohexane - ethyl acetate with volume ratios of 99:1, 97:3, 95:5, 90:10, 85:15, 80:20, 70:30, 60:40, and 0:100 to obtain C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, and C17, a total of 17 sub - fractions; (4) Subject the sub - fraction C10 obtained by eluting with cyclohexane - ethyl acetate with a volume ratio of 80:20 to medium - low pressure reverse - phase column chromatography, and elute it successively with methanol - water - formic acid with volume ratios of 35:65:0.1, 40:60:0.1, 45:55:0.1, 50:50:0.1, 60:40:0.1, 70:30:0.1, 80:20:0.1, 100:0:0 to obtain C10.1, C10.2, C10.3, C10.4, C10.5, C10.6, C10.7, C10.8, C10.9, C10.10, C10.11, C10.12, C10.13, C10.14, C10.15, C10.16, C10.17, C10.18, C10.19, C10.20, C10.21, C10.22, and C10.23, a total of 23 sub - fractions; (5) Subject the sub - fraction C10.9 obtained by eluting with methanol - water - formic acid with a volume ratio of 45:55:0.1 to preparative reverse - phase high - performance liquid chromatography, and elute it with acetonitrile - water - formic acid with a volume ratio of 32:68:0.1 at a flow rate of 10 mL / min to obtain the compound of formula (II).

2. A method for preparing compounds of formula (I) and formula (II), characterized in that, The structural formulas of the formula (I) and formula (II) are as follows: ; Specifically, it includes the following steps: (1) Take the dried bark of cinnamon and extract it by heating under reflux with 60% ethanol aqueous solution twice, 2 hours each time. After filtration, the filtrate is concentrated under reduced pressure to obtain a concentrated solution; (2) Extract the concentrated solution with dichloromethane and collect the extract; (3) Perform normal pressure silica gel column chromatography on the extract, and elute it successively with cyclohexane - ethyl acetate with volume ratios of 99:1, 97:3, 95:5, 90:10, 85:15, 80:20, 70:30, 60:40, and 0:100 to obtain C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, and C17, a total of 17 sub - fractions; (4) The sub-fraction C10 eluted with cyclohexane-ethyl acetate with a volume ratio of 80:20 was subjected to medium and low pressure reverse phase column chromatography, and the elution procedure was carried out successively with methanol-water-formic acid with volume ratios of 35:65:0.1, 40:60:0.1, 45:55:0.1, 50:50:0.1, 60:40:0.1, 70:30:0.1, 80:20:0.1, 100:0:0 to obtain C10.1, C10.2, C10.3, C10.4, C10.5, C10.6, C10.7, C10.8, C10.9, C10.10, C10.11, C10.12, C10.13, C10.14, C10.15, C10.16, C10.17, C10.18, C10.19, C10.20, C10.21, C10.22 and C10.23, a total of 23 sub-fractions; (5) The sub-fraction C10.9 eluted with methanol-water-formic acid with a volume ratio of 45:55:0.1 was prepared by reverse phase preparative high performance liquid chromatography, and eluted with acetonitrile-water-formic acid with a volume ratio of 32:68:0.1 at a flow rate of 10 mL / min to obtain the compound of formula (Ⅱ); (6) The sub-fractions C15 and C16 eluted with cyclohexane-ethyl acetate with a volume ratio of 60:40 were combined and subjected to medium and low pressure reverse phase column chromatography, and successively eluted with methanol-water-formic acid with volume ratios of 25:75:0.1, 30:70:0.1, 35:65:0.1, 40:60:0.1, 45:55:0.1, 50:50:0.1, 55:45:0.1, 60:40:0.1, 65:35:0.1, 70:30:0.1, 80:20:0.1, 100:0:0 to obtain C15&16.1, C15&16.2, C15&16.3, C15&16.4, C15&16.5, C15&16.6, C15&16.7, C15&16.8, C15&16.9, C15&16.10, C15&16.11, C15&16.12, C15&16.13, C15&16.14, C15&16.15, C15&16.16, C15&16.17, C15&16.18, C15&16.19 and C15&16.20, a total of 20 sub-fractions; (7) The sub-fraction C15&16.9 eluted with methanol-water-formic acid with a volume ratio of 40:60:0.1 was prepared by reverse phase preparative high performance liquid chromatography, and eluted with methanol-water-formic acid with a volume ratio of 45:55:0.1 at a flow rate of 8 mL / min to obtain the compound of formula (Ⅰ).

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