(1E)-1,5-diphenyl-1-penten-3-one and its pharmaceutical composition and its preparation method and application

Abstract

The present invention provides (1 E )-1,5-diphenyl-1-penten-3-one[(1 E )-1,5-Diphenyl-1-penten-3-one, PFX38] and its pharmaceutical composition and its preparation method and application, belong to the field of pharmaceutical technology. The present invention adopts the method of chromatographic separation to obtain Aquilaria sinensis Compound PFX38 was prepared from the ethanol extract of agarwood produced from the (Lour.) Spreng. agarwood germplasm. This compound has significant anti-inflammatory activity and can be used to prepare anti-inflammatory cosmetics or drugs.

Description

Technical field:

[0001] The present invention belongs to the field of medical technology, and specifically relates to (1E)-1,5-diphenyl-1-penten-3-one, a pharmaceutical composition thereof, a preparation method thereof, and an application thereof in the preparation of anti-inflammatory cosmetics or drugs. Background technology:

[0002] Inflammation refers to the body's defensive response to maintain tissue homeostasis when damaged, and excessive inflammatory responses can also trigger or aggravate various inflammatory diseases [Zhou Qin, Zeng Jia, Liu Zhidan, Wang Jitong, Zhang Yu, Zhao Fan, Wang Jiamiao, Liu Minchen, Du Ruofei. Research progress of bee venom peptide in the treatment of inflammatory diseases. Chinese Journal of Modern Applied Pharmacy, 2023, 40(9): 1270–1277]. Excessive production of nitric oxide (NO) by iNOS, one of the pro-inflammatory enzymes, can lead to a variety of diseases, including asthma, arthritis, multiple sclerosis, colitis, psoriasis, neurodegenerative diseases, and tumor development. Currently, widely used anti-inflammatory drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) have side effects such as peptic ulcer, liver and kidney damage, headache, and insomnia [Guo Yang, Peng Yanfeng, Yang Yongjing, Zhang Benyin, Zhang Dejun. Exploring the mechanism of action of Oxytropis falciparum flavonoids on inflammation based on network pharmacology and experimental verification. Chinese Journal of Food Additives, 2023, 34(5): 184–193]. Therefore, it is necessary to develop new anti-inflammatory drugs to provide new therapeutic strategies for the treatment of inflammatory diseases.

[0003] Aquilaria sinensis (Lour.) Spreng, a plant of the Thymelaeaceae family, contains resinous heartwood that has the effects of promoting qi and relieving pain, warming the middle and stopping vomiting, and promoting qi and relieving asthma. It is used to treat chest and abdominal distension and pain, stomach cold, vomiting, hiccups, and kidney deficiency due to qi reversal and asthma [National Pharmacopoeia Committee. Pharmacopoeia of the People's Republic of China (Part I). Beijing: China Medical Science and Technology Press. 2020, 192–193]. Aquilaria sinensis germplasm is an excellent variety of Aquilaria sinensis with the characteristics of fast agarwood formation and high yield [Feng Jian, Hou Wencheng, Chen Lan, Chen Xiqin, Yang Yun, Liu Yangyang, Wei Jianhe. Quality analysis and evaluation of aquilaria produced from aquilaria sinensis germplasm based on the Pharmacopoeia of the People's Republic of China. Modern Chinese Medicine, 2022, 24(3): 432–437].

[0004] There are no reports on the compound (1E)-1,5-diphenyl-1-penten-3-one in the prior art, let alone reports on its anti-inflammatory activity. Summary of the invention:

[0005] In view of the above-mentioned shortcomings of the prior art, the object of the present invention is to provide a compound (1E)-1,5-diphenyl-1-penten-3-one (this compound is discovered for the first time from the genus Aquilaria and belongs to the 1,5-diarylpentane class of components), a pharmaceutical composition thereof, a preparation method thereof, and its use in the preparation of anti-inflammatory cosmetics or drugs.

[0006] In order to achieve the above-mentioned object of the present invention, the present invention provides the following technical solutions:

[0007] The compound shown in the following structural formula is (1E)-1,5-diphenyl-1-penten-3-one,

[0008]

[0009] The present invention also provides a method for preparing compound (1E)-1,5-diphenyl-1-penten-3-one, which comprises the following steps:

[0010] Take agarwood produced by agarwood germplasm from Kynam, crush and sieve it, take 50g of powder each time and put it into the extraction tank, set the temperature to 40℃, the extraction pressure to 35MPa, extract for 3h, and the flow rate of supercritical carbon dioxide to 200L per hour. After the extraction is completed, open the exhaust valve at the bottom of the collection tank to collect the carbon dioxide extract PFX1. Repeat the experiment until all the powder is extracted, and finally obtain PFX1;

[0011] The dried medicinal residue after supercritical carbon dioxide extraction was extracted with 90% ethanol in an ultrasonic extractor at 60°C for 30 minutes each time. The extract was filtered through a Buchner funnel and the operation was repeated five times. The filtrate was then cooled at 60°C to recover the solvent under reduced pressure to obtain the dry extract PFX2.

[0012] The dried extract PFX2 was separated by column chromatography using 80-100 mesh normal phase silica gel, and eluted with dichloromethane, acetone and methanol in that order. The column chromatography was segmented, and the solvent was recovered under reduced pressure to obtain three fractions, namely, a dichloromethane elution fraction, an acetone elution fraction and a methanol elution fraction.

[0013] The dichloromethane elution portion was separated by column chromatography using 100-200 mesh normal phase silica gel, eluted with petroleum ether-ethyl acetate, and the elution gradient was 15:1→0:1. The eluents were combined according to the thin layer chromatography development to obtain 9 components A1~A9; component A2 was the petroleum ether-ethyl acetate elution portion with a 15:1 ratio, and was further chromatographed on a YMC reverse phase silica gel column, using methanol-water as the eluent, and the gradient elution was 40%→100%, and the eluent was 10 mL per bottle. , TLC analysis, the same parts were combined to obtain 9 components A2-1 to A2-9; A2-4 was the 60% methanol elution part, and then it was chromatographed on a hydroxypropyl dextran gel column, eluted with methanol, and TLC analysis was performed. The eluates with the same spots were combined, and the solvent was removed under reduced pressure to obtain 5 components A2-4-1 to A2-4-5. Component A2-4-5 is compound (1E)-1,5-diphenyl-1-penten-3-one, namely PFX38.

[0014] The present invention also provides the use of the compound (1E)-1,5-diphenyl-1-penten-3-one in the preparation of anti-inflammatory drugs, and the use of the compound (1E)-1,5-diphenyl-1-penten-3-one in the preparation of cosmetics.

[0015] The present invention further provides a pharmaceutical composition comprising the compound (1E)-1,5-diphenyl-1-penten-3-one represented by the structural formula and a pharmaceutically acceptable carrier.

[0016] And, use of the pharmaceutical composition in preparing anti-inflammatory drugs.

[0017] Also, a method for preparing the pharmaceutical composition, the method comprising the following steps:

[0018] Take agarwood produced by agarwood germplasm from Kynam, crush and sieve it, take 50g of powder each time and put it into the extraction tank, set the temperature to 40℃, the extraction pressure to 35MPa, extract for 3h, and the flow rate of supercritical carbon dioxide to 200L per hour. After the extraction is completed, open the exhaust valve at the bottom of the collection tank to collect the carbon dioxide extract PFX1. Repeat the experiment until all the powder is extracted, and finally obtain PFX1;

[0019] The dried medicinal residue after supercritical carbon dioxide extraction was extracted with 90% ethanol in an ultrasonic extractor at 60°C for 30 minutes each time. The extract was filtered through a Buchner funnel and the operation was repeated five times. The filtrate was then cooled at 60°C to recover the solvent under reduced pressure to obtain the dry extract PFX2.

[0020] The dried extract PFX2 was separated by column chromatography using 80-100 mesh normal phase silica gel, and eluted with dichloromethane, acetone and methanol in that order. The column chromatography was segmented, and the solvent was recovered under reduced pressure to obtain three fractions, namely, a dichloromethane elution fraction, an acetone elution fraction and a methanol elution fraction.

[0021] The dichloromethane elution portion was separated by column chromatography on 100-200 mesh normal phase silica gel, eluted with petroleum ether-ethyl acetate, with an elution gradient of 15:1→0:1. The eluents were combined according to the thin layer chromatography development to obtain 9 components A1~A9; component A2 was the elution portion of petroleum ether-ethyl acetate 15:1, and was further chromatographed on a YMC reverse phase silica gel column, with methanol-water as the eluent, with a gradient elution of 40%→100%, with 10 mL of eluent per bottle, and TLC After expansion analysis, the same parts were combined to obtain 9 components A2-1 to A2-9; A2-4 was the 60% methanol elution part, which was then subjected to hydroxypropyl dextran gel column chromatography and eluted with methanol. After TLC expansion analysis, the eluates with the same spots were combined, and the solvent was removed under reduced pressure to obtain 5 components A2-4-1 to A2-4-5. Component A2-4-5 is compound (1E)-1,5-diphenyl-1-penten-3-one, and then a pharmaceutically acceptable carrier was added.

[0022] The pharmaceutical composition provided herein comprises the aforementioned compound and a pharmaceutically acceptable carrier. In the present invention, the pharmaceutically acceptable carrier is preferably a solid, semisolid, or liquid diluent, filler, or pharmaceutical product adjuvant. The present invention does not particularly limit the pharmaceutically acceptable carrier; any pharmaceutically acceptable carrier and / or excipient well known in the art that is nontoxic and inert to humans and animals may be selected.

[0023] The present invention has no particular limitation on the preparation method of the pharmaceutical composition. The compound can be directly mixed with a pharmaceutically acceptable carrier. The present invention has no particular limitation on the mixing process. The pharmaceutical composition can be obtained by selecting a process well known in the art.

[0024] The present invention provides the use of the pharmaceutical composition described in the above technical solution in the preparation of anti-inflammatory drugs. There is no special limitation on the method of the application, and any method well known in the art can be used.

[0025] In the present invention, when the compound or pharmaceutical composition is used to prepare an anti-inflammatory drug, the content of the compound in the drug is preferably 0.1-99%; in the pharmaceutical composition, the content of the compound in the pharmaceutical composition is preferably 0.5-90%. The pharmaceutical composition of the present invention is preferably used in the form of a dosage per unit body weight. In the present invention, the prepared drug is preferably administered by injection (intravenous injection, intramuscular injection) and oral administration.

[0026] The present invention also provides cosmetics comprising the compound (1E)-1,5-diphenyl-1-penten-3-one represented by the structural formula and common cosmetic excipients, as well as applications in the preparation of cosmetics.

[0027] In the present invention, the cosmetic preparation method can be a conventional cosmetic preparation method. First, compound (1E)-1,5-diphenyl-1-penten-3-one is prepared according to the above method, and then common cosmetic excipients are added.

[0028] Compared with the prior art, the present invention has the following advantages:

[0029] 1.(1E)-1,5-Diphenyl-1-penten-3-one (PFX38) was discovered from the genus Aquilaria for the first time.

[0030] 2. The anti-inflammatory activity of (1E)-1,5-diphenyl-1-penten-3-one (PFX38) is better than that of the positive control drug.

[0031] 3. (1E)-1,5-Diphenyl-1-penten-3-one (PFX38) has a simple structure, a simple and easy preparation method, low cost, high efficiency, and is conducive to large-scale production. Description of the drawings:

[0032] Figure 1 Schematic diagram of the chemical structure of the compound (1E)-1,5-diphenyl-1-penten-3-one (PFX38) of the present invention. Specific implementation method:

[0033] To better understand the essence of the present invention, the following test examples and examples of the present invention are used in conjunction with the accompanying drawings to further illustrate the preparation method, structural identification and anti-inflammatory activity of the compound PFX38 of the present invention, as well as the preparation method and pharmaceutical composition of the present invention, but the present invention is not limited to these test examples and examples.

[0034] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions of the present invention. Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0035] Example 1:

[0036] Preparation process of PFX1, PFX2 and compound (1E)-1,5-diphenyl-1-penten-3-one (PFX38).

[0037] One kilogram of agarwood from the Aquilaria sinensis (Lour.) Spreng. variety was crushed and sieved, and 50 grams of the powder was placed in an extraction tank at a temperature of 40°C and an extraction pressure of 35 MPa for 3 hours. The supercritical carbon dioxide flow rate was set to 200 liters per hour. After extraction, the exhaust valve at the bottom of the collection tank was opened to collect the carbon dioxide extract (PFX1). The experiment was repeated until all the powder was extracted, resulting in a total of 87 grams of PFX1.

[0038] The dried medicinal residue (591.0 g) after supercritical carbon dioxide extraction was extracted with 90% ethanol in an ultrasonic extractor at 60°C for 30 min each time. The extract was filtered through a Buchner funnel and the operation was repeated 5 times. The filtrate was decompressed and the solvent was recovered at 60°C to obtain a dry extract (PFX2) with a quantitative value of 248.9 g.

[0039] 245.3 g of the dried extract (PFX2) was separated by column chromatography using 80-100 mesh normal phase silica gel. The product was eluted in the order of dichloromethane, acetone and methanol. The column chromatography was performed and the solvent was recovered under reduced pressure to obtain three fractions: the dichloromethane elution fraction (A, 92.1 g), the acetone elution fraction (B, 139.2 g) and the methanol elution fraction (C, 12.0 g).

[0040] The dichloromethane elution fraction (A, 90.1 g) was separated by column chromatography on 100-200 mesh normal phase silica gel using a petroleum ether-ethyl acetate gradient of 15:1 → 0:1. The eluates were combined based on thin layer chromatography (TLC) results to yield nine fractions (A1-A9). Fraction A2 (petroleum ether-ethyl acetate (15:1) elution fraction, 249.3 mg) was chromatographed on a YMC reverse phase silica gel column using a methanol-water gradient of 40% → 100% (10 mL per vial). The eluate was analyzed by TLC. Identical fractions were combined to yield nine fractions (A2-1-A2-9). A2-4 (60% methanol elution fraction, 70.2 mg) was chromatographed on a hydroxypropyl dextran gel column using methanol. The eluates were combined and the solvent removed under reduced pressure to yield five fractions (A2-4-1-A2-4-5). Component A2-4-5 is compound (1E)-1,5-diphenyl-1-penten-3-one (PFX38) (2.5 mg).

[0041] Compound (1E)-1,5-diphenyl-1-penten-3-one (PFX38) (structural formula see Figure 1 ) spectral data and structural identification:

[0042] Compound (1E)-1,5-diphenyl-1-penten-3-one [(1E)-1,5-Diphenyl-1-penten-3-one, PFX38], yellow oil; molecular formula: C 17 H 16 O, CAS No. 39728-15-9; 1 H NMR (CDCl3, 800MHz)δ H 7.55(1H,d,J=16.2Hz,H-1),7.53–7.52(2H),7.40–7.39(3H),7.31–7.29(2H),7.2 5–7.24(2H),7.22–7.20(1H),6.75(1H,d,J=16.2Hz,H-2),3.02(4H,s,H2-4,H2-5); 13 C NMR (CDCl3, 201 MHz) δ C 199.5(C,C-3),142.9(CH,C-1),141.4(C,C-1″),134.6(C,C-1′),130.7(CH,C-2),129.1(CH,C-3′,5′),128.7(CH, EI-MS m / z(rel.int.)236[M] + (26), 131(100), 103(52), 91(30), 77(40). Its nuclear magnetic resonance (NMR) data were basically consistent with the data reported in the literature [Li W., Wu X.-F. Ruthenium-catalyzed conjugate hydrogenation of α, β-enones by insitu generated dihydrogen from paraformaldehyde and water. European Journal of Organic Chemistry, 2015: 331–335], and it was identified as (1E)-1,5-diphenylpent-1-en-3-one.

[0043] Example 2:

[0044] The anti-inflammatory test method is as follows:

[0045] 1. Experimental Principle

[0046] Nitric oxide (NO) has a wide range of important biological regulatory functions and plays an important role in inflammation, tumors and cardiovascular systems. When immune cells are stimulated by microbial endotoxins, inflammatory mediators, etc., a large amount of induced nitric oxide synthase (iNOS) will be generated to produce NO for immune response. Therefore, inhibiting NO production is a direct indicator of the anti-inflammatory activity of the compound. Mouse mononuclear macrophage RAW264.7 was treated with LPS lipopolysaccharide to induce the production of nitric oxide synthase, and the test compound was added at the same time. The culture medium was aspirated and the absorbance value was measured at a wavelength of 570nm by the Griess method to detect nitrite (NO). 2- ).

[0047] 2. Reagents

[0048] Mouse mononuclear macrophage RAW264.7 cells were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences, and DMEM medium and fetal bovine serum were purchased from BI. Griess reagent, lipopolysaccharide (LPS), and the positive control drug NG-monomethyl-L-arginine (L-NMMA) were purchased from Sigma.

[0049] 3. Experimental Methods

[0050] RAW264.7 cells were seeded into 96-well plates and stimulated with 1 μg / ml LPS. Test compounds (PFX1, PFX2, and PFX38) were added simultaneously (final concentrations starting at 50 μg / mL or 50 μM, diluted 2-fold). A drug-free group and an L-NMMA-positive control group served as controls. After overnight incubation, the culture medium was collected and assayed for NO production by measuring absorbance at 570 nm. MTS was added to the remaining culture medium to determine cell viability and to exclude potential toxic effects of the compounds on the cells.

[0051] NO production inhibition rate (%) = (OD 570 nm - Sample group OD 570 nm ) / OD of non-drug treated group 570 nm ×100%

[0052] IC 50 (50% concentration of inhibition) was calculated according to the Reed & Muench method.

[0053] The anti-inflammatory effects of PFX1, PFX2, and PFX38 are shown in Table 1. As can be seen from the table, the anti-inflammatory effect of compound (1E)-1,5-diphenyl-1-penten-3-one (PFX38) is better than that of the positive drug L-NMMA.

[0054] Table 1 IC of samples for inhibition of NO generation 50 value

[0055]

[0056] Formulation Examples

[0057] In the following formulation examples, conventional reagents were selected and the formulations were prepared according to conventional methods. This application example only demonstrates that the compound (1E)-1,5-diphenyl-1-penten-3-one (PFX38) of the present invention can be prepared into different formulations, and does not specifically limit the specific reagents and operations.

[0058] 1. The compound of the present invention (1E)-1,5-diphenyl-1-penten-3-one (PFX38) was dissolved in a small amount of DMSO, and then conventionally added with water for injection, finely filtered, and sterilized by filling to prepare an injection solution with a concentration of 0.5 to 5 mg / mL.

[0059] 2. Dissolve the compound (1E)-1,5-diphenyl-1-penten-3-one (PFX38) of the present invention in a small amount of DMSO, dissolve it in sterile water for injection, stir to dissolve, filter with a sterile suction funnel, and then filter aseptically. The resulting mixture is divided into ampoules, freeze-dried at low temperature, and sealed aseptically to obtain a powder for injection.

[0060] 3. The compound of the present invention (1E)-1,5-diphenyl-1-penten-3-one (PFX38) was added to the excipient at a weight ratio of 9:1 to prepare a powder.

[0061] 4. The compound (1E)-1,5-diphenyl-1-penten-3-one (PFX38) of the present invention was added to the excipients at a weight ratio of 5:1, and the mixture was granulated and tableted.

[0062] 5. The compound of the present invention (1E)-1,5-diphenyl-1-penten-3-one (PFX38) was prepared into an oral solution according to a conventional oral solution preparation method.

[0063] 6. The compound (1E)-1,5-diphenyl-1-penten-3-one (PFX38) of the present invention was added to the excipients at a weight ratio of 5:1 to prepare capsules.

[0064] 7. The compound of the present invention (1E)-1,5-diphenyl-1-penten-3-one (PFX38) was added to the excipient at a weight ratio of 5:1 to prepare granules.

[0065] Cosmetic Formulation Examples

[0066] 1. Whitening cream formula containing the compound of the present invention (1E)-1,5-diphenyl-1-penten-3-one (PFX38) (W%):

[0067]

[0068] The cosmetics of the present invention are prepared by conventional methods for preparing cosmetics.

[0069] 2. Emulsion formula containing the compound of the present invention (1E)-1,5-diphenyl-1-penten-3-one (PFX38) (W%):

[0070]

[0071]

[0072] The cosmetics of the present invention are prepared by conventional methods for preparing cosmetics.

[0073] As can be seen from the above examples, the present invention provides (1E)-1,5-diphenyl-1-penten-3-one (PFX38), its preparation method and application, and pharmaceutical compositions and applications thereof. The compounds provided by the present invention have varying degrees of inhibitory effects on inflammatory cells and can be combined with pharmaceutically acceptable carriers or excipients to form pharmaceutical compositions for the preparation of anti-inflammatory drugs.

[0074] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. The compound shown in the following structural formula (1 E )-1,5-diphenyl-1-penten-3-one preparation method, It is characterized by: The method comprises the following steps: Agarwood from the agarwood germplasm of Kynam was taken, crushed and sieved, and 50 g of powder was taken each time and placed in an extraction tank. The temperature was set at 40 °C, the extraction pressure was 35 MPa, and the extraction was carried out for 3 h. The flow rate of supercritical carbon dioxide was set to 200 L per hour. After the extraction was completed, the exhaust valve at the bottom of the collection tank was opened to collect the carbon dioxide extract PFX1. The experiment was repeated until all the powder was extracted, and PFX1 was finally obtained. The dried medicinal residue after supercritical carbon dioxide extraction was extracted with 90% ethanol in an ultrasonic extractor at 60°C for 30 min each time. The extract was filtered through a Buchner funnel and the operation was repeated five times. The filtrate was then cooled at 60°C to recover the solvent and obtain the dry extract PFX2. The dried extract PFX2 was separated by column chromatography using 80-100 mesh normal phase silica gel, and eluted with dichloromethane, acetone, and methanol in that order. The column chromatography was segmented, and the solvent was recovered under reduced pressure to obtain three fractions: a dichloromethane elution fraction, an acetone elution fraction, and a methanol elution fraction. The dichloromethane elution fraction was separated by column chromatography on 100-200 mesh normal phase silica gel, eluted with petroleum ether-ethyl acetate, elution gradient 15:1→0:1, and the eluents were combined according to the thin layer chromatography development to obtain 9 components A1~A9; component A2 was the petroleum ether-ethyl acetate elution fraction at 15:1, and then subjected to YMC reverse phase silica gel column chromatography, using methanol-water as eluent, 40%→100% gradient elution, 10 mL of eluent per bottle, TLC development analysis, and the same fractions were combined to obtain 9 components A2-1~A2-9; A2-4 was the 60% methanol elution fraction, and then subjected to hydroxypropyl dextran gel column chromatography, eluted with methanol, TLC development analysis, and the eluents with the same spots were combined, and the solvent was removed under reduced pressure to obtain 5 components A2-4-1~A2-4-5. Component A2-4-5 is compound (1 E )-1,5-diphenyl-1-penten-3-one.

2. Compound (1 E A method for preparing a pharmaceutical composition of )-1,5-diphenyl-1-penten-3-one and a pharmaceutically acceptable carrier, characterized in that: The method comprises the following steps: Agarwood from the agarwood germplasm of Kynam was taken, crushed and sieved, and 50 g of powder was taken each time and placed in an extraction tank. The temperature was set at 40 °C, the extraction pressure was 35 MPa, and the extraction was carried out for 3 h. The flow rate of supercritical carbon dioxide was set to 200 L per hour. After the extraction was completed, the exhaust valve at the bottom of the collection tank was opened to collect the carbon dioxide extract PFX1. The experiment was repeated until all the powder was extracted, and PFX1 was finally obtained. The dried medicinal residue after supercritical carbon dioxide extraction was extracted with 90% ethanol in an ultrasonic extractor at 60°C for 30 min each time. The extract was filtered through a Buchner funnel and the operation was repeated five times. The filtrate was then cooled at 60°C to recover the solvent and obtain the dry extract PFX2. The dried extract PFX2 was separated by column chromatography using 80-100 mesh normal phase silica gel, and eluted with dichloromethane, acetone, and methanol in that order. The column chromatography was segmented, and the solvent was recovered under reduced pressure to obtain three fractions: a dichloromethane elution fraction, an acetone elution fraction, and a methanol elution fraction. The dichloromethane elution fraction was separated by column chromatography on 100-200 mesh normal phase silica gel, eluted with petroleum ether-ethyl acetate, elution gradient 15:1→0:1, and the eluents were combined according to the thin layer chromatography development to obtain 9 components A1~A9; component A2 was the petroleum ether-ethyl acetate elution fraction at 15:1, and then subjected to YMC reverse phase silica gel column chromatography, using methanol-water as eluent, 40%→100% gradient elution, 10 mL of eluent per bottle, TLC development analysis, and the same fractions were combined to obtain 9 components A2-1~A2-9; A2-4 was the 60% methanol elution fraction, and then subjected to hydroxypropyl dextran gel column chromatography, eluted with methanol, TLC development analysis, and the eluents with the same spots were combined, and the solvent was removed under reduced pressure to obtain 5 components A2-4-1~A2-4-5. Component A2-4-5 is compound (1 E )-1,5-diphenyl-1-penten-3-one, and then adding a pharmaceutically acceptable carrier.

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