Polycyclic polyisopentenyl phloroglucinol compound as well as preparation method and application thereof

Abstract

The invention discloses a polycyclic polyisopentenyl phloroglucinol compound as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The method comprises the following steps: by taking a dry overground part of hypericum monogynum as a raw material, performing percolation extraction and concentration to obtain an extract, suspending the extract in water to obtain a suspension, and performing extraction and concentration to obtain a petroleum ether part extract; the extract is taken and subjected to separation through a positive and negative phase silica gel column, MCI medium-pressure column chromatography and Sephadex LH-20 gel column chromatography and purification through high performance liquid chromatography, the polycyclic polyisopentenyl phloroglucinol compound is prepared, and the structure and configuration of the compound are determined by means of a spectrum analysis technology, quantum chemistry calculation, X-ray single crystal diffraction and the like. The compound can inhibit TNF-alpha protein to play an immunosuppressive role, and can be used as an immunosuppressive drug.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to a polycyclic polyisopentenyl phloroglucinol compound and a preparation method and application thereof. Background Art

[0002] Psoriasis is a chronic, difficult to treat and highly recurrent autoimmune inflammatory skin disease. The number of patients has been on the rise in my country in recent years. It is most common during adolescence and requires lifelong treatment. It is usually induced by genetic factors, infection, immune inflammation, endocrine factors, drinking, smoking, drugs and mental stress. The main manifestations are thickening of the stratum corneum, erythema and scaling. It can occur all over the body, and is more common on the scalp and extensor side of the limbs. It can cause malnutrition and concurrent anxiety and depression. If not treated, it can progress to severe psoriasis, with irreversible damage to organs such as the liver and kidneys. Currently, it is mainly treated with glucocorticoids, immunosuppressants, and biological agents, and there is no specific treatment.

[0003] Acute lung injury (ALI) is caused by various direct and indirect factors that damage alveolar epithelial cells and capillary endothelial cells, resulting in diffuse pulmonary interstitial and alveolar edema, leading to acute hypoxic respiratory insufficiency. Endothelial inflammation and dysfunction play an important role in the development of ALI.

[0004] Hypericum, the whole herb of Hypericum perforatum of the family Garciniaceae. Many species of Hypericum are medicinal plants. Traditional Chinese medicine believes that plants of this genus have the effects of clearing away heat and detoxifying, astringing and stopping bleeding, and promoting dampness. It is used to treat hemoptysis, blood transformation, intestinal wind bleeding, traumatic bleeding, rheumatic bone pain and other symptoms. In recent years, studies have found that plants of this genus have pharmacological activities such as anti-depression, anti-tumor, anti-viral, analgesic, antibacterial, and anti-inflammatory. Studies have shown that the chemical components of Hypericum mainly include two categories: phloroglucinol and ketone. Among them, phloroglucinol is mainly composed of rich and diverse polycyclic polyisopentenyl phloroglucinol, which is also considered to be the main material basis for the many pharmacological activities of berry Hypericum. However, there are currently no reports on the use of phloroglucinol drugs for the prevention and treatment of psoriasis and acute lung injury. Summary of the invention

[0005] The purpose of the present invention is to provide a polycyclic polyisopentenyl phloroglucinol compound and a preparation method and application thereof, so as to solve the problems existing in the above-mentioned prior art.

[0006] To achieve the above object, the present invention provides the following solutions:

[0007] One of the technical solutions of the present invention is a polycyclic polyisopentenyl phloroglucinol compound, the structural formula of which is as follows:

[0008]

[0009] The second technical solution of the present invention is a method for preparing the polycyclic polyisopentenyl phloroglucinol compound, comprising the following steps:

[0010] (1) using the dried aerial part of Hypericum perforatum as raw material, extracting and concentrating to obtain an extract, suspending the extract in water to obtain a suspension, extracting and concentrating to obtain a crude extract;

[0011] (2) separating the crude extract by silica gel column chromatography, and eluting with petroleum ether-ethyl acetate in a volume ratio of 10:1, 5:1, 3:1, 2:1, 1:1, and 1:2 to obtain six main fractions A to F;

[0012] (3) Fraction C was separated by MCI medium pressure column chromatography and gradient eluted with methanol-water at a volume ratio of 30:70, 50:50, 70:30, and 90:10 to obtain four subfractions C1 to C4;

[0013] (4) using a Sephadex LH-20 gel column to separate fraction C3 into seven main fractions C3-1 to C3-7;

[0014] (5) Fraction C3-2 was subjected to medium-pressure reverse phase chromatography to obtain ten subfractions C3-2A to C3-2J;

[0015] (6) Fraction C3-2C was purified by preparative HPLC to obtain compound 2;

[0016] (7) Fraction C3-2F was purified by preparative HPLC to obtain compounds 1, 4 and fraction C3-2F2;

[0017] (8) Fraction C3-2F2 was purified by preparative HPLC column to obtain compound 5;

[0018] (9) Fraction C3-2G was purified by preparative HPLC column to obtain compound 6;

[0019] (10) Fraction D was separated by MCI medium pressure column chromatography, and gradient eluted with methanol-water at a volume ratio of 30:70, 50:50, 70:30, and 90:10 to obtain four sub-fractions D1 to D4; fraction D3 was separated into five main fractions D3-1 to D3-5 using a Sephadex LH-20 gel column; fraction D3-3 was subjected to medium pressure reverse phase chromatography to obtain eight sub-fractions D3-3A to D3-3H;

[0020] (11) Fraction D3-3D was purified using a preparative HPLC column to obtain compound 3.

[0021] The third technical solution of the present invention is the use of the polycyclic polyisopentenyl phloroglucinol compound in the preparation of drugs for preventing and treating psoriasis.

[0022] A fourth technical solution of the present invention is the use of the polycyclic polyisopentenyl phloroglucinol compound in the preparation of drugs for preventing and treating acute lung injury.

[0023] Based on the above technical solution, the present invention has the following technical effects:

[0024] The present invention obtains 6 new compounds (1-6) by separating and purifying the ethanol extract of Hypericum perforatum. Using a variety of spectral analysis methods and other methods, it is determined that the structure is a polycyclic polyisopentenyl phloroglucinol compound. By evaluating the TNF-α-induced L929 cell cytotoxicity protection activity of compounds 1-6, it is found that compounds 1-6 can effectively inhibit TNF-α, among which compound 5 can alleviate the skin lesions of psoriasis mice and protect LPS-induced lung damage in mice, proving that these compounds can be used as lead compounds for the development of anti-inflammatory immune drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0026] Figure 1 The X-ray single crystal diffraction structures of compounds 1 and 2.

[0027] Figure 2 The experimental ECD spectra and calculated ECD spectra of compounds 4-6. A represents the experimental ECD spectrum and calculated ECD spectrum of compound 4, and B represents the comparison of experimental ECD spectra of compounds 4-6.

[0028] Figure 3 Experiments for compounds 5 and 6 13 C NMR and calculations 13 Linear correlation diagram of C NMR chemical shift. A represents the experimental 13 C NMR and 2R,4S,5S,12S,17S,19S,20R,23R,24S,M)-5 calculation 13 Linear correlation diagram of C NMR chemical shift, B represents the experimental results of compound 5 13 C NMR and 2R,4S,5S,12R,17S,19S,20R,23R,24S,M)-5 calculation 13 Linear correlation diagram of C NMR chemical shift, C represents the experimental value of compound 6 13C NMR and 2R,4S,5S,12S,17S,19S,20R,23R,24S,M)-6 calculations 13 Linear correlation diagram of C NMR chemical shift, D represents the experimental data of compound 6 13 C NMR and 2R,4S,5S,12R,17S,19S,20R,23R,24S,M)-6 calculations 13 Linear correlation plot of C NMR chemical shifts.

[0029] Figure 4 CP3 calculations and MAE based on calculated and experimental NMR chemical shifts for compounds 5 and 6 ΔΔδ Parameter analysis.

[0030] Figure 5 Comparison of experimental VCD / IR and calculated VCD / IR for compounds 5 and 6.

[0031] Figure 6 A shows the cytotoxicity of compounds 1–6 tested at a fixed concentration of 40 μM in L929 cells; B shows the protective effect of compounds 1–6 against TNF-α-induced L929 cytotoxicity at 40 μM; C shows the protective effect of compound 5 against TNF-α-induced L929 cytotoxicity at different concentrations.

[0032] Figure 7 A is the appearance of the skin and spleen of mice in each group; B is the PASI score of each group; C is the HE and immunohistochemistry detection images.

[0033] Figure 8 The figures are HE and immunohistochemistry results of lung tissues of mice in each group. DETAILED DESCRIPTION

[0034] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0035] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0036] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0037] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present application description and examples are exemplary only.

[0038] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0039] The technical solutions described in the present invention, unless otherwise specified, are all conventional solutions in the art, and the reagents or raw materials used, unless otherwise specified, are purchased from commercial channels or have been disclosed.

[0040] The embodiment of the present invention provides a polycyclic polyisopentenyl phloroglucinol compound, the structural formula of which is shown below:

[0041]

[0042] The embodiment of the present invention also provides a method for preparing the polycyclic polyisopentenyl phloroglucinol compound, comprising the following steps:

[0043] (1) using the dried aerial part of Hypericum perforatum as raw material, extracting and concentrating to obtain an extract, suspending the extract in water to obtain a suspension, extracting and concentrating to obtain a crude extract;

[0044] (2) separating the crude extract by silica gel column chromatography, and eluting with petroleum ether-ethyl acetate in a volume ratio of 10:1, 5:1, 3:1, 2:1, 1:1, and 1:2 to obtain six main fractions A to F;

[0045] (3) Fraction C was separated by MCI medium pressure column chromatography and gradient eluted with methanol-water at a volume ratio of 30:70, 50:50, 70:30, and 90:10 to obtain four subfractions C1 to C4;

[0046] (4) using a Sephadex LH-20 gel column to separate fraction C3 into seven main fractions C3-1 to C3-7;

[0047] (5) Fraction C3-2 was subjected to medium-pressure reverse phase chromatography to obtain ten subfractions C3-2A to C3-2J;

[0048] (6) Fraction C3-2C was purified by preparative HPLC to obtain compound 2;

[0049] (7) Fraction C3-2F was purified by preparative HPLC to obtain compounds 1, 4 and fraction C3-2F2;

[0050] (8) Fraction C3-2F2 was purified by preparative HPLC column to obtain compound 5;

[0051] (9) Fraction C3-2G was purified by preparative HPLC column to obtain compound 6;

[0052] (10) Fraction D was separated by MCI medium pressure column chromatography, and gradient eluted with methanol-water at a volume ratio of 30:70, 50:50, 70:30, and 90:10 to obtain four sub-fractions D1 to D4; fraction D3 was separated into five main fractions D3-1 to D3-5 using a Sephadex LH-20 gel column; fraction D3-3 was subjected to medium pressure reverse phase chromatography to obtain eight sub-fractions D3-3A to D3-3H;

[0053] (11) Fraction D3-3D was purified using a preparative HPLC column to obtain compound 3.

[0054] In some specific embodiments, the conditions of the diafiltration extraction are: using 95% ethanol by volume for diafiltration extraction for 72 hours at a flow rate of 0.5 L / h.

[0055] In some specific embodiments, the extraction conditions are: extraction with petroleum ether, and the volume ratio of petroleum ether to the suspension is 1:1.

[0056] The embodiment of the present invention also provides the use of the polycyclic polyisopentenyl phloroglucinol compound in the preparation of a drug for preventing and treating psoriasis.

[0057] The embodiment of the present invention also provides the use of the polycyclic polyisopentenyl phloroglucinol compound in the preparation of a drug for preventing and treating acute lung injury.

[0058] In some specific embodiments, pharmaceutically acceptable excipients are also included.

[0059] Example 1

[0060] The dried aerial part of Hypericum perforatum (20 kg) was used as raw material, and the extract was extracted by filtration with a volume fraction of 95% ethanol. The filtration extraction time was 72 h, and the filtration extraction flow rate was 0.5 L / h. The extract was concentrated and suspended in water to obtain a suspension, which was extracted 3 times with petroleum ether (1:1, v / v) and concentrated to obtain a crude extract (310 g). The crude extract was separated by silica gel column chromatography and gradient eluted with petroleum ether (PE)-ethyl acetate (EtOAc) (10:1, 5:1, 3:1, 2:1, 1:1, 1:2, v / v) to obtain six main fractions (AF).

[0061] Fraction C (PE-EtOAc, 3:1, v / v) was separated by MCI medium pressure column chromatography and gradient eluted with methanol-water (30:70, 50:50, 70:30, 90:10, v / v) system to obtain four sub-fractions (C1-C4). Fraction C3 was separated into seven main fractions (C3-1-C3-7) using Sephadex LH-20 gel column (CH3OH-CH2Cl2, 1:1, v / v). Fraction C3-2 was separated by medium pressure reverse phase chromatography (CH3OH-H2O, 50:50-90:10, v / v, 6h, 25mL / min) to obtain ten sub-fractions (C3-2A-C3-2J).

[0062] Fraction C3-2C was purified by preparative HPLC column (MeCN-H2O, 56:44, v / v, 8 mL / min) to obtain compound 2 (3.7 mg, t R 26.3min).

[0063] Fraction C3-2F was purified by preparative HPLC column (MeCN-H2O, 63:37, v / v, 8 mL / min) to obtain compound 1 (2.4 mg, t R 23.8min)、4(4.3mg,t R 26.1min) and fraction C3-2F2. Fraction C3-2F2 was purified by preparative HPLC column (MeOH-H2O, 80:20, v / v, 8 mL / min) to give compound 5 (13.7 mg, t R 36.5min). Fraction C3-2G was purified by preparative HPLC column (MeCN-H2O, 63:37, v / v, 8mL / min) to obtain compound 6 (6.5mg, t R 36.5min).

[0064] Fraction D (PE-EtOAc, 2:1, v / v) was separated by MCI medium pressure column chromatography and gradient eluted with methanol-water (30:70, 50:50, 70:30, 90:10, v / v) system to obtain four sub-fractions (D1-D4). Fraction D3 was separated into five main fractions (D3-1-D3-5) using Sephadex LH-20 gel column (CH3OH-CH2Cl2, 1:1, v / v). Fraction D3-3 was separated by medium pressure reverse phase chromatography (CH3OH-H2O, 50:50–90:10, v / v, 6h, 25mL / min) to obtain eight sub-fractions (D3-3A-D3-3H).

[0065] Fraction D3-3D was purified by preparative HPLC column (MeCN-H2O, 55:45, v / v, 8 mL / min) to give compound 3 (5.8 mg, t R 33.7min).

[0066] Example 2

[0067] Structural identification of compounds 1–6:

[0068] Compounds 1–6 were tested by nuclear magnetic resonance, mass spectrometry, optical rotation, infrared spectrum, ultraviolet spectrum, circular dichroism and other data, and compounds 1 and 2 were tested by X-ray single crystal diffraction data (such as Figure 1 As shown), VCD calculation, DP4+ calculation and corresponding CP3 calculation and MAE calculation were performed on compounds 5 and 6. ΔΔδ Parameter analysis (such as Figure 4 ), ECD data calculation was performed on compound 4 (as shown Figure 2 The structures of compounds 1–6 were determined as follows:

[0069]

[0070] Compound 1* (Hypermonol F): colorless crystals; melting point: 153–155°C; –48.3 (methanol, c 0.1); UV (methanol) λ max (logε): 201(4.29)nm; IR (potassium bromide)ν max : 3408, 1968, 2921, 2851, 1762, 1734, 1466, 1382, 1104, 914cm –1 ;(+)-HRESIMS m / z 483.2352[M+Na] + (C 26 H 36 O7 + The calculated value of m / z is 483.2359);1 H and 13 C NMR data are shown in Table 1.

[0071] Compound 2* (Hypermonol G): colorless crystals; melting point: 126–127°C; +41.5 (methanol, c 0.1); UV (methanol) λ max (logε): 202(4.36)nm; IR (potassium bromide)ν max : 3365, 2920, 2850, 1759, 1726, 1958, 1468, 1381, 1237, 1125, 917cm –1 ;(+)-HRESIMS m / z483.2350[M+Na] + (C 26 H 36 O7 + Calculated value for m / z 483.2359); 1 H and 13 C NMR data are shown in Table 1.

[0072] Compound 3* (Hypermonol H): colorless oil; +124.7 (methanol, c 0.1); UV (methanol) λ max (logε): 201(4.43)nm; IR (potassium bromide)ν max : 3433, 1968, 2923, 2852, 1761, 1725, 1459, 1383, 1123, 1015, 899cm –1 ;(+)-HRESIMS m / z 483.2358[M+Na] + (C 26 H 36 O7 + The calculated value of m / z is 483.2359); 1 H and 13 C NMR data are shown in Table 2.

[0073] Compound 4* (Hypermonol I): colorless oil; +134.4 (methanol, c 0.1); UV (methanol) λ max (logε): 202(4.27)nm; IR (potassium bromide)ν max :3443, 2971, 2391, 1765, 1725cm –1 ;(+)-HRESIMS m / z483.2352[M+Na] + (C 26H 36 O7 + Calculated value for m / z 483.2359); 1 H and 13 C NMR data are shown in Table 2.

[0074] Compound 5* (Hypermonol J): colorless oil; +42.5 (methanol, c 0.1); UV (methanol) λ max (logε): 202(4.38)nm; IR (potassium bromide)ν max : 3431, 2921, 2851, 1764, 1737, 1697, 1658, 1467, 1381, 1109, 913cm –1 ;(+)-HRESIMS m / z 497.2511[M+Na] + (C 27 H 38 O7 + The calculated value of m / z is 497.2515); 1 H and 13 C NMR data are shown in Table 3.

[0075] Compound 6* (Hypermonol K): colorless oil; +119.2 (methanol, c 0.1); UV (methanol) λ max (logε): 201(4.55)nm; IR (potassium bromide)ν max :3444, 2967, 2921, 1765, 1738, 1647, 1465, 1381, 1232, 1109, 913cm –1 ;(+)-HRESIMS m / z 497.2517[M+Na] + (C 27 H 38 O7 + The calculated value of m / z is 497.2515); 1 H and 13 C NMR data are shown in Table 3.

[0076] Table 1 Compounds 1 and 2 1 H NMR and 13 C NMR data (δinppm, Jin Hz)

[0077]

[0078]

[0079] Table 2 Compounds 3 and 4 1 H NMR and 13 C NMR data (δinppm, Jin Hz)

[0080]

[0081] Table 3 Compounds 5 and 6 13 C NMR and 13 C NMR data (δ in ppm)

[0082]

[0083]

[0084] Example 3

[0085] 3.1 Toxicity assay of compounds 1–6 on L929 cells

[0086] L929 cells in the logarithmic growth phase were cultured at 1.5×10 5 The cells were inoculated at a density of 100 / mL in a 96-well plate. After 24 h of stable growth, 40 μM of compounds 1-6 were added and incubated for 24 h. The absorbance was measured according to the instructions of the CCK-8 reagent. The survival rate (%) = OD 化合物 / OD 对照 × 100% was used to evaluate the toxicity of compounds in L929 cell assay.

[0087] The results are as follows Figure 6 As shown in Figure A, compounds 1-6 had no toxic effects at 40 μM.

[0088] 3.2 Compounds 1–6 protect L929 cells from TNF-α-induced cytotoxicity

[0089] L929 cells in the logarithmic growth phase were cultured at 1.5×10 5 The cells were inoculated at a density of 100 / mL in a 96-well plate. After stable growth for 24 h, 40 μM of compounds 1–6 were added, and then 2 ng / mL TNF-α and 1 μg / mL actinomycin D were added and incubated for 24 h. The absorbance was measured according to the instructions of the CCK-8 reagent. The survival rate (%) = OD 化合物 / OD 对照 ×100% was used to evaluate the protective effect of the compounds on TNF-α-induced L929 cell toxicity.

[0090] The results are as follows Figure 6 As shown in Figure B, compounds 1–6 protected L929 cells from the killing effect of TNF-α to a certain extent at 40 μM, among which compound 5 had the best effect.

[0091] 3.3 Compound 5 protects L929 cell cytotoxicity induced by TNF-α

[0092] L929 cells in the logarithmic growth phase were cultured at 1.5×10 5 The cells were inoculated at a density of 100 / mL in a 96-well plate. After 24 h of stable growth, different concentrations of compound 5, 2 ng / mL TNF-α and 1 μg / mL actinomycin D were added and incubated for 24 h. The absorbance was measured according to the instructions of the CCK-8 reagent. The survival rate (%) was calculated as OD 化合物 / OD 对照 ×100% was used to evaluate the protective effect of the compounds on TNF-α-induced L929 cell toxicity.

[0093] The results are as follows Figure 6 As shown in C, compound 5 still has a protective effect on TNF-α-induced L929 cell toxicity at 2.5 μM, demonstrating its potential to inhibit TNF-α.

[0094] Example 4

[0095] 4.1 Alleviating effect of compound 5 on skin lesions in psoriasis mice

[0096] After one week of adaptive feeding in an SPF barrier environment, 8-week-old Balb / C male mice were shaved of their mid-back hair with a mouse shaver and randomly divided into 4 groups: blank control group (Normal), imiquimod model group (IMQ), positive drug group (tapinarof), and compound 5 group (1%).

[0097] The mice in the model group, positive drug group and compound 5 group were smeared with 5% IMQ cream (62.5 mg / mouse) once a day for 7 consecutive days to establish a psoriasis-like mouse model.

[0098] The positive drug and compound 5 were dissolved in a mixed solution of 60% anhydrous ethanol and 40% glycerol to a mass volume concentration of 1%. The control group was smeared with vaseline of the same volume as IMQ.

[0099] The dynamic changes of the back skin lesions of mice were observed and recorded before daily administration, and PASI scores were performed according to the severity of psoriasis in mice, i.e., the scales, erythema, and thickening of the back skin lesions. The skin lesion tissues of mice were obtained for HE staining and immunohistochemical detection.

[0100] The results are as follows Figure 7As shown, mice in the IMQ group showed obvious skin thickening and erythema, and the clinical severity score (CSS) continued to rise, while compound 5 improved psoriatic dermatitis in a dose-dependent manner, as shown by reduced severity of skin erythema and scaling, reduced thickness of the skin stratum spinosum, and reduced CSS. HE staining results showed that the skin lesions of mice in the IMQ group had significant histological features such as epidermal hyperplasia, scaling, and inflammatory cell infiltration. However, these symptoms were improved after treatment with compound 5 and the positive drug tapinarof. According to the immunohistochemical results, the compound 5 treatment group showed downregulation of Ki67 and decreased IL-17 expression, indicating that compound 5 can alleviate the symptoms of epidermal hyperplasia in psoriasis by inhibiting excessive proliferation of epidermal cells.

[0101] 4.2 Compound 5 protects against LPS-induced acute lung injury in mice

[0102] After one week of adaptive feeding in an SPF barrier environment, 7-week-old Balb / C male mice were randomly divided into 4 groups: blank control group (Normal), LPS model group (LPS), positive drug group (DEX), and compound 5 group (10 mg / kg).

[0103] After 3 days of intragastric administration, each group was intraperitoneally injected with LPS 12.5 mg / kg to establish an acute lung injury model in mice. Lung tissues of mice were collected for HE staining and immunohistochemical detection.

[0104] The results are as follows Figure 8 As shown, the lung tissue morphology of mice with acute lung injury was also improved, TNF-α expression was reduced, and inflammatory infiltration was reduced; ZO-1 and Occludin expression was increased, the barrier was repaired, the F4 / 80 ratio was decreased, and the number of lung macrophages was also reduced.

[0105] The effects of other compounds (compounds 1-4 and compound 6) on alleviating skin lesions in psoriasis mice and protecting against LPS-induced acute lung injury in mice were slightly weaker than those of compound 5, but they were able to achieve the expected therapeutic effects.

[0106] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation methods of the present invention. For ordinary technical users in the relevant field, other different forms of changes or modifications can be made on the basis of the above description. It is not necessary and impossible to list all the implementation methods here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A polycyclic polyisopentenyl phloroglucinol compound, characterized in that: Its structural formula is as follows:

2. The method for preparing the polycyclic polyisopentenyl phloroglucinol compound according to claim 1, characterized in that: The following steps are involved: (1) using the dried aerial part of Hypericum perforatum as raw material, extracting and concentrating to obtain an extract, suspending the extract in water to obtain a suspension, extracting and concentrating to obtain a crude extract; (2) separating the crude extract by silica gel column chromatography, and eluting with petroleum ether-ethyl acetate in a volume ratio of 10:1, 5:1, 3:1, 2:1, 1:1, and 1:2 to obtain six main fractions A to F; (3) Fraction C was separated by MCI medium pressure column chromatography and gradient eluted with methanol-water at a volume ratio of 30:70, 50:50, 70:30, and 90:10 to obtain four subfractions C1 to C4; (4) using a Sephadex LH-20 gel column to separate fraction C3 into seven main fractions C3-1 to C3-7; (5) Fraction C3-2 was subjected to medium-pressure reverse phase chromatography to obtain ten subfractions C3-2A to C3-2J; (6) Fraction C3-2C was purified by preparative HPLC to obtain compound 2; (7) Fraction C3-2F was purified by preparative HPLC to obtain compounds 1, 4 and fraction C3-2F2; (8) Fraction C3-2F2 was purified by preparative HPLC column to obtain compound 5; (9) Fraction C3-2G was purified by preparative HPLC column to obtain compound 6; (10) Fraction D was separated by MCI medium pressure column chromatography, and gradient eluted with methanol-water at a volume ratio of 30:70, 50:50, 70:30, and 90:10 to obtain four sub-fractions D1 to D4; fraction D3 was separated into five main fractions D3-1 to D3-5 using a Sephadex LH-20 gel column; fraction D3-3 was subjected to medium pressure reverse phase chromatography to obtain eight sub-fractions D3-3A to D3-3H; (11) Fraction D3-3D was purified using a preparative HPLC column to obtain compound 3.

3. The preparation method according to claim 2, characterized in that: The conditions of the diafiltration extraction are: using 95% ethanol by volume for diafiltration extraction, the time is 72 hours, and the flow rate is 0.5 L / h.

4. The preparation method according to claim 2, characterized in that: The extraction conditions are: extraction with petroleum ether, and the volume ratio of petroleum ether to the suspension is 1:

1.

5. Use of the polycyclic polyisopentenyl phloroglucinol compound as claimed in claim 1 in the preparation of a medicament for preventing and treating psoriasis.

6. Use of the polycyclic polyisopentenyl phloroglucinol compound as claimed in claim 1 in the preparation of a medicament for preventing and treating acute lung injury.

7. The use according to claim 5 or 6, characterized in that: The medicine also includes pharmaceutically acceptable excipients.

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