CN-110522743-B - Application of toyophyllol as active ingredient in immunosuppressant

Abstract

The invention discloses application of toyophyllitol as an active ingredient in immunosuppressants, which screens out toyophyllitol with remarkable calmodulin phosphatase (CN) inhibition activity from the cashew fruits, has an immunosuppression effect equivalent to that of an immunosuppressant cyclosporin A widely used clinically, and has the effect of playing an immunosuppression role in targeting a CN/NFAT signal channel through action mechanism research, has weak cytotoxicity on spleen and is an efficient and low-toxicity immunosuppressant.

Inventors

• XU JING
• LI GANG
• CEN JUREN
• DENG QIN

Assignees

• 海南大学

Dates

Publication Date

20260508

Application Date

20190919

Claims (1)

1. 1. The application of the toyophyllin as an active ingredient in the preparation of immunosuppressive drugs.

Description

Application of toyophyllol as active ingredient in immunosuppressant Technical Field The invention relates to application of toyophyllol, in particular to application of toyophyllol as an active ingredient in immunosuppressant. Background Calmodulin phosphatase (calcineurin, CN) is a Ca 2+ -and calmodulin-dependent serine/threonine-specific phosphatase which is extracted from yeast fermentation broth and is also commonly referred to as calmodulin phosphatase because of its high content in nerve tissue (Klee et al, 1979). When biochemists and neurobiologists studied this novel protein, the immunosuppressant cyclosporin a (CsA), which was inadvertently newly discovered, was combined into a complex with intracellular cyclophilin (cytosolic protein), thereby having a remarkable immunosuppressive effect, and was widely used in organ transplantation surgery (Borel et al, 1976;Handschumacher et al, 1984). Phosphorylation and dephosphorylation of proteins is an extremely important regulatory mechanism in vital activities, which permeates almost every vital activity process as a result of the co-regulation of the dynamic actions of protein kinases (PKase) and protein phosphatases (protein phosphatase, PPase). Protein phosphatases are currently known in fewer classes than protein kinases, and little research is known about the regulatory mechanisms in cellular vital activities. Calmodulin phosphatase (Calcineurin, CN) as a member of the family of protein phosphatases, whose activity is directly regulated by the intracellular second messenger Ca 2+/CaM (calmodulin), plays an extremely important role in immunomodulation, learning memory, cell signal transduction and the like, and, due to its nature, structure and functional particularities, attracts great interest and importance to numerous researchers, and has been studied extensively in the discovery of its substrates, the study of physiological functions, the study of enzyme activity inhibitors and the like, wherein the most breakthrough development has been the study effort to identify calmodulin phosphatase as a specific target enzyme of the immunosuppressive drugs cyclosporin A, csA, FK506 in 1990. However, existing calcineurin phosphatase inhibitors such as cyclosporin a and tacrolimus are currently commonly used immunosuppressants in clinic, but have various adverse reactions such as nephrotoxicity, hyperglycemia, non-specificity to cells, and the like. The invention takes calmodulin phosphatase as target enzyme, screens out compounds with the activity of inhibiting calmodulin phosphatase (CN) in vitro from the cashew, and deeply researches the mechanism of the compounds, thereby having great significance for researching and revealing the function and action mechanism of the calmodulin phosphatase in life activities and providing a new way for developing new high-efficiency low-toxicity immunosuppressants. Disclosure of Invention In view of this, the present invention proposes the use of tolterodine as an active ingredient in immunosuppressants. The technical scheme of the invention is realized as follows: The application of the toyophyllin as an active ingredient in immunosuppressant, wherein the inhibitor is an immunosuppressant drug. According to the invention, through the primary screening of immunosuppressive activity by taking immune calmodulin phosphatase (CN) as a target enzyme and taking pNPP as a substrate, the monomer compound separated from the cashew nut is subjected to the primary screening of immunosuppressive activity, and the fact that the toyol shows better immunosuppressive activity in the primary screening process is found. Further research on the toyol is continued, a PMA/Io induced Jurkat cell activation model is established, and the CN vitality change, the IL-2 content change and the NFAT protein expression condition in Jurkat cells are detected, so that the action mechanism of the toyol is explained. The toyophyllitol has no cytotoxic activity to Jurkat cells or no effect of promoting cell proliferation or inhibiting cell growth within the concentration range of 1-40 mu m. In the toxicity evaluation of the leaf-spitting alcohol on the Jurkat cells, the invention treats the Jurkat cells with different concentrations of the leaf-spitting alcohol for 48 hours, and discovers that the survival rate of the Jurkat cells is not significantly different within the concentration range (1-40 mu M) adopted under different treatment time conditions, and the survival rate of the Jurkat cells is more than 90%. As the concentration of the compound continued to rise, the high dose group (75, 100. Mu.M) of toyol exhibited a slight inhibitory effect on Jurkat cells, with cell viability decreasing below 90%. Showing that the toyophyllitol has no cytotoxic activity on Jurkat cells and no effect of promoting cell proliferation or inhibiting cell growth in the concentration range of 1-40 mu M. Leaf-spitting alcohol is used for inhibiting the activity of Jurkat