Use of jincheshen glycoside in inhibiting inflammation reaction of brain striatum

Abstract

This invention belongs to the field of pharmaceutical technology and discloses the use of ginsenoside in the preparation of drugs that inhibit inflammatory responses in the striatum of the brain. Specifically, it discloses the use of ginsenoside (Formula I) in the preparation of drugs for inhibiting inflammatory responses in the striatum of the brain. 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), monocyte chemotactic factor-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) in the striatum of mouse brain tissue, exhibiting significant activity in inhibiting inflammatory responses in the striatum of the brain. Therefore, this compound can be used to prepare drugs for the prevention and / or treatment of inflammatory responses in the striatum of the brain, possessing 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 striatum of the brain. Background Technology

[0002] The striatum, located deep within the brain, comprises the caudate nucleus, putamen, and globus pallidus, and is primarily responsible for regulating motor, cognitive, and emotional responses. Situated in the basal ganglia, it is a component of the extrapyramidal system. Damage to the striatum can lead to dystonia, manifesting as hypertonia, reduced facial expression, involuntary movements, and tremors of the hands and feet. Inflammatory factors and adhesion molecules involved in striatal inflammation include interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), single-cell chemokine-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-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 inflammatory responses in the striatum of the brain. Summary of the Invention

[0005] This invention utilizes an intraperitoneal injection LPS-induced mouse inflammatory response model to evaluate the effect of ginsenoside on the inflammatory response of the striatum. 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 drugs and other products related to the inhibition of inflammatory responses in the striatum of the brain.

[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 caused by inflammatory reactions in the brain striatum.

[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 inflammatory responses in the striatum of the brain.

[0011]

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

[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 inflammatory responses in the striatum, characterized in that the pharmaceutical composition comprises the compound sclerotinib (or a pharmaceutically acceptable salt thereof) of the first aspect formula (I), 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 in the striatum, characterized in that the pharmaceutical composition comprises the compound scleroside 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 brain striatal inflammatory response-related factors IL-1β, IL-6, TNFα, MCP-1 and ICAM-1, indicating that ginsenoside has significant anti-brain striatal inflammatory response activity.

[0016] In addition, drugs and other products prepared with ginsenoside as the active ingredient for the prevention and / or treatment of diseases related to the inhibition of inflammatory responses in the striatum 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 inhibiting inflammatory responses in the striatum of the brain. Attached Figure Description

[0024] Figure 1 Effects of ginsenoside on IL-1β levels in LPS-induced striatum 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.

[0025] Figure 2 Effects of ginsenoside on IL-6 levels in LPS-induced striatum 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 striatum tissue of mice. Data are expressed as mean ± SD. Compared with the control group, #P<0.05; compared with the LPS model group, **P<0.01.

[0027] Figure 4 Effects of sclerotin on MCP-1 levels in LPS-induced striatum 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.

[0028] Figure 5 Effects of ginsenoside on ICAM-1 levels in LPS-induced striatum tissue of mice. Data are expressed as mean ± SD. Compared with the control group, #P<0.05; compared with the LPS model group, *P<0.05. Detailed Implementation

[0029] Effect of ginsenoside on LPS-induced inflammatory response in mouse striatum

[0030] 1. Experimental Methods

[0031] 1.1 Animal Grouping and Administration

[0032] Reagent LPS is a product of Sigma Company; the detection kits for IL-1β, IL-6, TNFα, MCP-1 and ICAM-1 are products of Gett-Xeno Biotechnology Co., Ltd.

[0033] Experimental animals: Adult male BALB / c mice were purchased from SPF (Beijing) Biotechnology Co., Ltd. (Animal Quality Certificate No.: SCXK (Beijing) 2024-0001). The animals were reared under normal conditions at a temperature of (25±1℃), a relative humidity of 55% to 65%, with a 12-hour light-dark cycle, and free access to food and water.

[0034] 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 administered by gavage 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. At 6 hours after LPS injection, the brain striatum tissue was collected and frozen in a -80℃ refrigerator for subsequent ELISA detection.

[0035] 1.2 ELISA Detection

[0036] The tissue from the specific site 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, MCP-1, and ICAM-1. The operation was carried out in accordance with 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 biotinylated antibody working solution, add HRP-labeled secondary antibody to all wells except the blank well, 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.

[0037] 2. Experimental Results:

[0038] Compared with the normal control group, the levels of inflammatory response-related factors IL-1β, IL-6, TNFα, MCP-1, and ICAM-1 in the striatum tissue of the LPS model group mice were significantly increased; while the levels of POL 20 mg·kg were significantly increased. -1 All treatment groups reduced the level of IL-1β, an inflammation-related factor, in the striatum of the mouse brain induced by LPS (Table 1). Figure 1 ), IL-6 (Table 2, Figure 2 ), TNFα (Table 3, Figure 3 MCP-1 (Table 4) Figure 4 ), ICAM-1 (Table 5, Figure 5 The increase of ).

[0039] Table 1. Effects of POL on IL-1β levels in LPS-induced striatum of mice.

[0040] Group IL-1β (pg / mg protein) normal control group 75.81±21.63 LPS model group 232.2±32.97## LPS+POL 20mg / kg group 169.0±23.89**

[0041] Table 2. Effects of POL on IL-6 levels in LPS-induced striatum of mice.

[0042]

[0043]

[0044] Table 3. Effects of POL on TNFα levels in LPS-induced striatum of mice.

[0045] Group TNFα (pg / mg protein) normal control group 29.98±13.70 LPS model group 63.20±27.00# LPS+POL 20mg / kg group 19.99±4.998**

[0046] Table 4. Effects of POL on MCP-1 levels in LPS-induced striatum of mice.

[0047] Group MCP-1 (pg / mg protein) normal control group 74.59±75.75 LPS model group 563.1±120.4## LPS+POL 20mg / kg group 3729±8587**

[0048] Table 5. Effects of POL on ICAM-1 levels in LPS-induced striatum of mice.

[0049] Group ICAM-1 (pg / mg) normal control group 137.2±109.7 LPS model group 507.2±290.2# LPS+POL 20mg / kg group 223.3±147.1* .

Claims

1. 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 inflammatory responses in the striatum of the brain.

2. 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 responses in the brain striatum.

3. The use of a pharmaceutical composition in the preparation of a drug for inhibiting inflammatory responses in the striatum, 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 in the striatum, 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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