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Application of epoxydiene taken as inhibitor of proinflammatory mediators

An epoxydiene, inflammation technology, applied in anti-inflammatory agents, non-central analgesics, medical preparations containing active ingredients, etc., can solve problems such as unreported anti-inflammatory physiological activity

Inactive Publication Date: 2011-04-20
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The compound MycoE was first reported in 1999 (Cai et al., Tetrahedron Letters, 1999, 40, 1479-1482). It was isolated from the fermentation broth of a rare fungus OS-F66617, but the literature did not report that it has anti-inflammatory physiological properties active

Method used

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  • Application of epoxydiene taken as inhibitor of proinflammatory mediators
  • Application of epoxydiene taken as inhibitor of proinflammatory mediators
  • Application of epoxydiene taken as inhibitor of proinflammatory mediators

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Embodiment 1, epoxy diene cytotoxicity experiment

[0028] The cytotoxicity of epoxydiene was detected by MTT assay.

[0029] The test method is as follows:

[0030] RAW264.7 cells (1×10 5 cells / well) into 96-well culture plate for overnight culture, add LPS (100ng / ml) and different concentrations of MycoE (0.1, 1, 5, 10μmol / L, use DMSO as blank control) to act together for 24h or different concentrations of MycoE (0.1, 1, 5, 10 μmol / L) act alone for 24 hours, then add MTT to a final concentration of 0.5 mg / ml for 4 hours, add solution (10% SDS, 0.01mol / L HCL) at 100 μl / well and measure 560nm overnight The absorbance value at (OD 560 ).

[0031] OD 560 Can reflect the growth of cells, so by comparing OD 560 Value to judge whether MycoE has cytotoxicity.

[0032] For the results of the MTT method, see figure 1 , 2 . The test results show that epoxy diene has no cytotoxicity to RAW264.7 cells at the concentration of 0.1-10 μmol / L.

Embodiment 2

[0033] Example 2, the application of epoxydiene in inhibiting the inflammatory response of RAW264.7 cells induced by bacterial lipopolysaccharide

[0034] In the present invention, by detecting the change of the concentration of the cell pro-inflammatory mediator, whether the epoxy diene can inhibit the inflammatory response of the RAW264.7 cell is determined.

[0035] The test method is as follows:

[0036] 1) MycoE concentration gradient. RAW264.7 cells (1×10 5 cells / well) into a 96-well culture plate, after 24h, add LPS to a final concentration of 100ng / ml to stimulate for 6h, and at the same time add different concentrations of MycoE (0.1, 1, 5, 10μmol / L, using DMSO as a blank control), and observe Effect of MycoE on expression of pro-inflammatory mediators stimulated by LPS. The concentrations of three proinflammatory mediators were detected by ELISA detection kit: tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cell culture supernatant, interleukin-1β (IL-...

Embodiment 3

[0041] Example 3, the application of epoxy diene in inhibiting the inflammatory response in mice

[0042] The invention uses a mouse survival rate test and a serum proinflammatory mediator detection test to determine whether the epoxy diene can inhibit the mouse inflammatory response.

[0043] The test method is as follows:

[0044] 1) Mouse survival rate experiment. SPF grade BALB / c mice were used for experiments, and the mice were divided into two groups, with 10 mice in each group: the first group was injected with LPS at 10 mg / kg mouse body weight; the second group was injected with 15 mg / kg mouse weight The body weight was injected with MycoE, and 30 minutes later, LPS was injected at 10 mg / kg mouse body weight. After injection of LPS, the survival of the mice was observed every 12 hours for 5 consecutive days.

[0045] 2) Detection of pro-inflammatory mediators in mouse serum. SPF grade BALB / c mice were used for the experiment, and the mice were divided into two grou...

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Abstract

The invention discloses application of epoxydiene taken as an inhibitor of proinflammatory mediators, and relates to a compound, namely the epoxydiene, in particular to application of the epoxydiene taken as the inhibitor of the proinflammatory mediators in medical field. The invention provides the application of the epoxydiene taken as the inhibitor of the proinflammatory mediators, in particular application in preparing a medicament for treating inflammatory diseases mediated by the proinflammatory mediators such as endotoxin shock and the like, and application in preparing a medicament fortreating inflammatory diseases mediated by the proinflammatory mediators such as rheumatoid arthritis and the like. A pharmacological experiment proves that the epoxydiene has important adjustment effect on the processes of inflammations by inhibiting the expression of a plurality of the proinflammatory mediators, and can be used for preparing anti-inflammatory medicaments. The compound can be obtained by separating from fungus fermentation products, and can also be chemically synthesized.

Description

technical field [0001] The invention relates to a compound epoxydiene (Mycoepoxydiene, abbreviated as MycoE), in particular to the use of an epoxydiene as an inhibitor of proinflammatory mediators in the field of medicine. Background technique [0002] Inflammatory response is one of the important components of the body's immune system. The body regulates it through various channels, but when the inflammatory response is uncontrollable, it will lead to various diseases in the body, such as rheumatoid arthritis (rheumatoid arthritis) , inflammatory bowel disease (inflammatory bowel diseases), neurodegenerative disorders (neurodegenerative disorders) and septic shock (septic shock syndrome), etc. Long-term inflammatory response stimulation can also induce body cancer, which seriously threatens people's physical and mental health Health (Monaco, et al., Curr Drug Targets Inflamm Allergy, 2004, 3, 35-42; Schwartsburd et al., et al., Cancer Metastasis Rev, 2003, 22, 95-102), ther...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61P1/00A61K31/366A61P25/00A61P43/00A61P29/00A61P19/04
Inventor 俞春东黄耀坚赵扬陈强陈腾辉沈月毛
Owner XIAMEN UNIV
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