A polycyclic polyisopentenyl phloroglucinol compound and its preparation method and application

Abstract

The present invention discloses a polycyclic polyisopentenyl phloroglucinol compound and its preparation method and application, belonging to the field of biomedicine technology. The dried aerial part of Hypericum perforatum is used as raw material, and an extract is obtained after diafiltration extraction and concentration, and the extract is suspended in water to obtain a suspension, and a petroleum ether extract is obtained after extraction and concentration; the extract is taken and subjected to positive and reverse phase silica gel column, MCI medium pressure column chromatography, Sephadex LH-20 gel column chromatography separation and high performance liquid chromatography purification to obtain a polycyclic polyisopentenyl phloroglucinol compound, and the structure and configuration of the compound are determined by means of spectral analysis technology, quantum chemical calculation and X-ray single crystal diffraction. This type of compound can inhibit TNF-α protein from exerting an immunosuppressive effect and has the use as an immunosuppressive drug.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, 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 relapsing autoimmune inflammatory skin disease, with an increasing number of patients in my country in recent years. It is most common during adolescence and requires lifelong treatment. It is typically triggered by genetic factors, infection, immune inflammation, endocrine factors, alcohol consumption, smoking, medications, and mental stress. Symptoms include thickening of the stratum corneum, erythema, and scaling. It can occur throughout the body, but is more common on the scalp and extensor surfaces of the limbs. It can cause malnutrition and concurrent anxiety and depression. Without treatment, it can progress to severe psoriasis, causing irreversible damage to organs such as the liver and kidneys. Currently, treatments primarily include glucocorticoids, immunosuppressants, and biologics, with no specific cure available.

[0003] Acute lung injury (ALI) is caused by a variety of direct and indirect factors that damage alveolar epithelial cells and capillary endothelial cells, resulting in diffuse interstitial and alveolar edema and acute hypoxic respiratory failure. Endothelial inflammation and dysfunction play a key role in the development of ALI.

[0004] Hypericum wilfordii, the whole herb of the plant Hypericum perforatum, belongs to the family Garciniaaceae. Several species of the genus Hypericum are medicinal plants. Traditional Chinese medicine believes that plants in this genus have the effects of clearing heat and detoxifying, astringing and stopping bleeding, and promoting diuresis. They are used to treat hemoptysis, blood stasis, intestinal bleeding, traumatic bleeding, rheumatic bone pain, and other symptoms. Recent studies have found that plants in this genus have pharmacological activities such as antidepressant, antitumor, antiviral, analgesic, antibacterial, and anti-inflammatory. Studies have shown that the chemical components of Hypericum wilfordii mainly include two categories: phloroglucinol and ketones. Among them, phloroglucinols are mainly composed of rich and diverse polycyclic polyisopentenyl phloroglucinols, which are also considered to be the main material basis for the numerous pharmacological activities of Hypericum wilfordii berries. 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 shown below:

[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) The crude extract was separated by silica gel column chromatography and eluted with petroleum ether-ethyl acetate in a gradient 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) Fraction C3 was separated into seven main fractions, C3-1 to C3-7, using a Sephadex LH-20 gel column;

[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 using a preparative HPLC column to obtain compounds 1, 4, and fraction C3-2F2;

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

[0018] (9) Fraction C3-2G was purified using a 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 subfractions 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 subfractions D3-3A to D3-3H;

[0020] (11) Fractions D3-3D were 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 isolated and purified six new compounds (1–6) from an ethanol extract of Hypericum perforatum. Using various spectral analysis techniques and other methods, their structures were confirmed to be polycyclic polyisopentenyl phloroglucinol compounds. Evaluation of the protective activity of compounds 1–6 against TNF-α-induced L929 cytotoxicity revealed that compounds 1–6 could effectively inhibit TNF-α. Compound 5, in particular, alleviated skin lesions in psoriatic mice and protected against LPS-induced lung injury in mice, demonstrating that these compounds could serve as lead compounds for the development of anti-inflammatory immunotherapies. 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 following briefly introduces the drawings required for use in the embodiments. 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 any creative work.

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

[0027] Figure 2 The experimental and calculated ECD spectra of compounds 4–6. A represents the experimental and calculated ECD spectra of compound 4, and B represents the comparison of the 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. Among them, A represents the experimental 13 C NMR and 2R,4S,5S,12S,17S,19S,20R,23R,24S,M)-5 calculations 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 calculations 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 MAEs for compounds 5 and 6 based on calculated and experimental NMR chemical shifts ΔΔδ Parameter analysis.

[0030] Figure 5 Comparison of experimental 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 against L929 cells; B shows the protective effect of compounds 1–6 against TNF-α-induced L929 cell toxicity at 40 μM; C shows the protective effect of compound 5 against TNF-α-induced L929 cell toxicity 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 Figures are the 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 rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

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

[0036] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice 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 any conflict with any incorporated document, the contents 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 without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the present invention. The present description and examples are intended to be illustrative only.

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

[0039] Unless otherwise specified, the technical solutions described in the present invention are all conventional solutions in the field, and the reagents or raw materials used, unless otherwise specified, are purchased from commercial channels or are publicly available.

[0040] 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) The crude extract was separated by silica gel column chromatography and eluted with petroleum ether-ethyl acetate in a gradient 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) Fraction C3 was separated into seven main fractions, C3-1 to C3-7, using a Sephadex LH-20 gel column;

[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 using a preparative HPLC column to obtain compounds 1, 4, and fraction C3-2F2;

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

[0051] (9) Fraction C3-2G was purified using a 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 subfractions 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 subfractions D3-3A to D3-3H;

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

[0054] In some specific embodiments, the conditions for 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 embodiments of the present invention also provide the use of the polycyclic polyisopentenyl phloroglucinol compound in the preparation of a drug for preventing and treating psoriasis.

[0057] The embodiments of the present invention also provide 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] Using 20 kg of the dried aerial parts of Hypericum perforatum, the extract was extracted by diafiltration with 95% ethanol for 72 hours at a flow rate of 0.5 L / h. The resulting extract was concentrated and suspended in water to obtain a suspension. The suspension was extracted three 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 using a gradient elution ratio of petroleum ether (PE)-ethyl acetate (EtOAc) (10:1, 5:1, 3:1, 2:1, 1:1, 1:2, v / v) to yield six major fractions (AF).

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

[0062] Fraction C3-2C was purified by preparative HPLC column (MeCN-H2O, 56:44, v / v, 8 mL / min) to give 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 give 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 Fraction C3-2G was purified by preparative HPLC column (MeCN-H2O, 63:37, v / v, 8 mL / min) to give compound 6 (6.5 mg, t R 36.5min).

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

[0065] Fractions D3-3D were 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] Structure 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 tests, 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 As shown), 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 O7Na + The calculated value for 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 O7Na + Calcd 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 O7Na + The calculated value for 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 O7Na + Calcd 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 O7Na + The calculated value for 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 O7Na + The calculated value for 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 (δ in ppm, Jin Hz)

[0077]

[0078]

[0079] Table 2 Compounds 3 and 4 1 H NMR and 13 C NMR data (δ in ppm, 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 a rate of 1.5×10 5 The cells were seeded at a density of 100 μg / 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 (%) was calculated as OD 化合物 / OD 对照 ×100% was used to evaluate the cytotoxicity of compounds in L929 cells.

[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 a rate of 1.5×10 5 The cells were seeded at a density of 100 μg / mL in a 96-well plate. After 24 h of stable growth, 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 (%) 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 cytotoxicity.

[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 a rate of 1.5×10 5 The cells were seeded at a density of 100 μg / 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 cytotoxicity.

[0093] The results are as follows Figure 6 As shown in Figure 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 breeding 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 psoriasis-like mouse models.

[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 petroleum jelly of the same volume as IMQ.

[0099] Before daily dosing, the dynamic changes of the back skin lesions of the mice were observed and recorded. The PASI score was calculated based on the severity of psoriasis (i.e., the degree of scaling, erythema, and thickening of the back skin lesions). Lesion tissues of the mice were obtained for HE staining and immunohistochemistry.

[0100] The results are as follows Figure 7As shown, mice in the IMQ group showed significant skin thickening and erythema, and the clinical severity score (CSS) continued to rise, while compound 5 improved psoriatic dermatitis in a dose-dependent manner, manifested by reduced severity of skin erythema and scaling, reduced thickness of the skin spinous layer, 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 immunohistochemistry results, the compound 5 treatment group showed downregulation of Ki67 and decreased IL-17 expression, indicating that compound 5 can alleviate the epidermal hyperplasia symptoms of psoriasis by inhibiting excessive proliferation of epidermal cells.

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

[0102] After 7-week-old Balb / C male mice were adapted to be raised in an SPF barrier environment for one week, they 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] Three days after oral gavage, each group received an intraperitoneal injection of 12.5 mg / kg LPS to establish an acute lung injury model in mice. Lung tissues were collected for HE staining and immunohistochemistry.

[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 worse 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 the purpose of clearly illustrating the present invention and are not intended to limit the implementation methods of the present invention. A person skilled in the art will be able to make other variations or modifications based on the above description. It is not necessary and impossible to enumerate all implementation methods here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the claims of the present invention.

Claims

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

2. The method for preparing the polycyclic polyisopentenyl phloroglucinol compound according to claim 1, wherein: The following steps are involved: (1) The dried aerial part of Hypericum perforatum is used as raw material, and the extract is extracted by filtration with 95% ethanol by volume, and concentrated to obtain an extract, the extract is suspended in water to obtain a suspension, and the crude extract is extracted with petroleum ether and concentrated; (2) The crude extract was separated by silica gel column chromatography and eluted with petroleum ether-ethyl acetate in a gradient 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) Fraction C3 was separated into seven main fractions, C3-1 to C3-7, using a Sephadex LH-20 gel column; (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 using a preparative HPLC column to obtain compounds 1, 4, and fraction C3-2F2; (8) Fraction C3-2F2 was purified by preparative HPLC to obtain compound 5; (9) Fraction C3-2G was purified using a 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 subfractions 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 subfractions D3-3A to D3-3H; (11) Fractions D3-3D were 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: time of 72 h and flow rate of 0.5 L / h.

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

1.

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

6. Use of the polycyclic polyisopentenyl phloroglucinol compound according to 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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