Use of jinsiheshen glycoside in inhibiting spleen inflammatory response

Abstract

This invention belongs to the field of pharmaceutical technology and discloses the use of ginsenoside in inhibiting splenic inflammation. Specifically, it discloses the use of compound (I) ginsenoside in the preparation of drugs that inhibit splenic inflammation. Pharmacological experiments have demonstrated that ginsenoside can significantly reduce the levels of LPS-induced inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), and monocyte chemotactic factor-1 (MCP-1) in mouse spleen tissue, exhibiting significant activity in inhibiting splenic inflammation. Therefore, this compound can be used to prepare drugs for the prevention and / or treatment of splenic inflammation and related conditions such as splenic abscess, splenic cyst, splenic tumor, and pancreatitis, demonstrating high clinical application value and development prospects.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology and relates to the use of ginsenoside A in inhibiting inflammatory responses in the spleen. Background Technology

[0002] Inflammation of the spleen is one of the most common pathological processes of the spleen, often occurring in conjunction with various infectious diseases. Based on its pathological characteristics and the speed of its progression, it can be divided into three types: acute inflammatory splenomegaly, necrotizing spleen, and chronic spleen. Common diseases associated with spleen inflammation include splenic abscess, splenic cyst, splenic tumor, and pancreatitis, with clinical manifestations such as poor mental state, fatigue, indigestion, abdominal distension, and abdominal pain. Inflammatory factors and adhesion molecules involved in splenic inflammation include interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), and single-cell chemokine-1 (MCP-1).

[0003] LPS is a major component of the cell wall of Gram-negative bacteria and a potent inducer of inflammatory responses. LPS-induced inflammatory responses have become a classic method for preparing animal models of inflammation and are widely used for screening, evaluating, and studying the mechanisms of drugs with anti-inflammatory activity. Animal studies have shown that intraperitoneal injection of LPS into mice can induce the expression of inflammatory cytokines in tissues.

[0004] Poliumoside (POL) is the main active ingredient in the traditional Chinese medicines *Cistanche sinensis* G. Beck and *Callicarpa kwangtungensis* Chun. Currently, there are few reports on the pharmacological activity of poliumoside, and there are no reports on its use in inhibiting splenic inflammatory responses. Summary of the Invention

[0005] This invention utilizes a mouse model of splenic inflammation induced by intraperitoneal injection of LPS to evaluate the anti-splenic inflammatory activity of ginsenoside. The structural formula of the compound ginsenoside involved in this invention is shown in Formula I:

[0006]

[0007] One of the technical problems to be solved by the present invention is to provide the use of the ginsenoside (I) in related drugs and other products for inhibiting inflammatory responses in the spleen.

[0008] The second technical problem to be solved by the present invention is to provide the use of the ginsenoside (I) in the prevention and / or treatment of diseases such as splenic abscess, splenic cyst, splenic tumor, and pancreatitis caused by splenic inflammatory reactions.

[0009] To solve the technical problem of this invention, the present invention provides the following technical solution:

[0010] The first aspect of the present invention is to provide the use of the compound sclerotinol as shown in formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a drug for inhibiting splenic inflammatory response.

[0011]

[0012] The present invention also provides the use of the compound sclerotinol as shown in formula (I) or a pharmaceutically acceptable salt thereof in the preparation of medicaments for the prevention and / or treatment of diseases caused by inflammatory reactions of the spleen.

[0013] The second aspect of the present invention is to provide the use of a pharmaceutical composition in the preparation of a drug for inhibiting splenic inflammatory response, characterized in that the pharmaceutical composition comprises the compound sclerotinic acid shown in the first aspect formula (I) or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

[0014] The present invention also provides the use of a pharmaceutical composition in the preparation of a medicament for the prevention and / or treatment of diseases caused by inflammatory responses of the spleen, characterized in that the pharmaceutical composition comprises the compound sclerotinic acid of the first aspect (I) or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

[0015] The compound ginsenoside of this invention can significantly reduce the elevated levels of LPS-induced inflammatory response-related factors IL-1β, IL-6, TNFα, and MCP-1 in spleen tissue, indicating that ginsenoside has significant anti-inflammatory activity against spleen inflammation.

[0016] In addition, drugs and other products prepared with ginsenoside as the active ingredient for the prevention and / or treatment of splenic inflammatory response and related diseases such as splenic abscess, splenic cyst, splenic tumor, and pancreatitis are also within the scope of protection of this invention.

[0017] This invention also relates to pharmaceutical compositions of the compounds of this invention and conventional pharmaceutical excipients or adjuvants.

[0018] Pharmaceutical compositions of the compounds of the present invention can be prepared according to methods known in the art. For this purpose, if desired, the compounds of the present invention can be combined with one or more solid or liquid pharmaceutical excipients and / or adjuvants to formulate suitable administration or dosage forms for use as human or veterinary medicine.

[0019] The compounds of this invention or pharmaceutical compositions containing them can be administered in unit dose form via enteral or non-enteric routes, such as oral, intramuscular, subcutaneous, nasal, oral mucosa, skin, peritoneum, or rectum.

[0020] The compounds of this invention or pharmaceutical compositions containing them can be administered via injection. Injection includes intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection, and acupoint injection, etc.

[0021] Dosage forms can be liquid or solid. Liquid dosage forms include true solutions, colloids, microparticles, emulsions, and suspensions. Other dosage forms include tablets, capsules, pellets, aerosols, pills, powders, solutions, suspensions, emulsions, granules, suppositories, and lyophilized powder injections.

[0022] The compounds of this invention can be formulated into conventional formulations, sustained-release formulations, controlled-release formulations, targeted formulations, and various microparticle delivery systems.

[0023] Beneficial technical effects: This compound has outstanding pharmacological activity and is suitable for use in splenic inflammatory reactions and the resulting splenic abscesses, splenic cysts, splenic tumors, pancreatitis, etc. Attached Figure Description

[0024] Figure 1 Effects of ginsenoside on IL-1β levels in LPS-induced mouse spleen tissue. Data are expressed as mean ± SD. Compared with the control group, ##P<0.01; compared with the LPS model group, *P<0.05.

[0025] Figure 2 Effects of ginsenoside on IL-6 levels in LPS-induced spleen tissue of mice. Data are expressed as mean ± SD. Compared with the control group, ##P<0.01; compared with the LPS model group, **P<0.01.

[0026] Figure 3 Effects of ginsenoside on TNFα levels in LPS-induced spleen tissue of mice. Data are expressed as mean ± SD. Compared with the control group, ##P<0.01; compared with the LPS model group, **P<0.01.

[0027] Figure 4 Effects of sclerotin on MCP-1 levels in LPS-induced mouse spleen tissue. Data are expressed as mean ± SD. Compared with the control group, ##P<0.01; compared with the LPS model group, **P<0.01. Detailed Implementation

[0028] Effect of ginsenoside on LPS-induced splenic inflammation in mice

[0029] 1. Experimental Methods

[0030] 1.1 Animal grouping and administration

[0031] The reagent LPS is a product of Sigma Company; the ELISA kits for detecting IL-1β, IL-6, TNFα and MCP-1 are products of Gett-X Yikesai Biotechnology Co., Ltd.

[0032] Experimental animals: Adult male BALB / c mice were purchased from Speifu (Beijing) Biotechnology Co., Ltd. (Certificate No.: SCXK (Beijing) 2024-0001). The animals were reared under normal conditions with a temperature of (25±1℃), a relative humidity of 55% to 65%, a 12-hour light-dark cycle, and free access to food and water.

[0033] Animal grouping and administration: After 3 days of adaptation, the animals were randomly divided into groups: normal control group (vehicle control), LPS model group (LPS), and POL 20mg / kg administration group (LPS+POL 20mg / kg). The normal control group and the LPS model group were intraperitoneally injected with an equal volume of vehicle (normal saline containing 0.1% Tween 80) for 7 consecutive days; the POL 20mg / kg administration group was intragastrically administered for 7 days. After the last administration, the LPS model group and the POL 20mg / kg group were intraperitoneally injected with 5mg / kg of LPS; the vehicle control group was intraperitoneally injected with an equal volume of normal saline. Spleen tissues were collected 6 hours after LPS injection and stored in a -80℃ refrigerator for subsequent ELISA detection.

[0034] 1.2 ELISA Detection

[0035] The tissue from the specific part of the mouse was weighed, and 1mL of pre-cooled normal saline was added per 100mg of tissue. A handheld homogenizer was used for grinding on ice to prepare a homogenate, which was centrifuged at 4500r / min and 4℃ for 15min, and the supernatant was collected. The BCA method was used to determine the protein content, and the ELISA kit was used to detect the contents of IL-1β, IL-6, TNFα and MCP-1. The operation was carried out according to the instructions, and the brief operation steps are as follows: Add the test sample or standard solutions of different concentration gradients to the 96-well ELISA plate, then add the biotinylated antibody working solution, incubate at room temperature for 120min, thoroughly wash and discard the sample and the biotinylated antibody working solution, add HRP-labeled secondary antibody except to the blank wells, and incubate at room temperature for 60min; discard the secondary antibody solution, wash thoroughly, add chromogenic substrate, and incubate at room temperature in the dark for 15min; detect the absorbance at 450nm within 10min after adding the stop solution, and calculate the content of inflammatory factors by drawing a standard curve.

[0036] 2 Experimental Results

[0037] Compared with the normal control group, the levels of inflammatory response-related factors IL-1β, IL-6, TNFα and MCP-1 in the spleen tissue of mice in the LPS model group were significantly increased; while in the POL 20mg·kg -1All treatment groups reduced the level of IL-1β, an inflammation-related factor, in LPS-induced mouse spleen tissue (Table 1). Figure 1 ), IL-6 (Table 2, Figure 2 ), TNFα (Table 3, Figure 3 MCP-1 (Table 4) Figure 4 The increase of ).

[0038] Table 1. Effects of POL on IL-1β levels in LPS-induced mouse spleen tissue.

[0039] Group IL-1β (pg / mg protein) normal control group 416.5±83.94 LPS model group 3297±287.7## LPS+POL 20mg / kg group 2841±352.9*

[0040] Table 2. Effects of POL on IL-6 levels in LPS-induced mouse spleen tissue.

[0041] Group IL-6 (pg / mg protein) normal control group 212.0±40.01 LPS model group 357.1±101.9## LPS+POL 20mg / kg group 192.4±22.39**

[0042] Table 3. Effects of POL on TNFα levels in LPS-induced mouse spleen tissue.

[0043]

[0044]

[0045] Table 4. Effects of POL on MCP-1 levels in LPS-induced mouse spleen tissue.

[0046] Group MCP-1 (pg / mg protein) normal control group 11.19±1.557 LPS model group 35.00±2.201## LPS+POL 20mg / kg group 23.71±3.269** .

Claims

1. The use of the compound sclerotinol as shown in formula (I) or a pharmaceutically acceptable salt thereof in the preparation of drugs for inhibiting inflammatory responses of the spleen.

2. The use of the compound sclerotinol as shown in formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the prevention and / or treatment of diseases caused by inflammatory responses of the spleen.

3. The use of a pharmaceutical composition in the preparation of a drug for inhibiting splenic inflammatory response, characterized in that, The pharmaceutical composition comprises the compound sclerotinol of formula (I) of claim 1 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

4. The use of a pharmaceutical composition in the preparation of a medicament for the prevention and / or treatment of diseases caused by inflammatory responses of the spleen, characterized in that, The pharmaceutical composition comprises the compound sclerotinol of formula (I) of claim 2 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

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