Immunosuppressive activity on the murine immune responses of glycyrol from Glycyrrhiza uralensis via inhibition of calcineurin activity.

Abstract

CONTEXT:

Calcineurin (CN), a unique protein phosphatase, plays an important role in immune regulation. Our laboratory has established an effective molecular drug-screening model based on CN activity.

OBJECTIVE:

Our aim is to search for an effective immunosuppressant from Glycyrrhiza uralensis (Leguminosae).

MATERIALS AND METHODS:

As guided by CN inhibitory test, an active compound was purified and identified as glycyrol. Immunosuppressive activity of glycyrol in vitro was assayed by T lymphocytes proliferation and mixed lymphocyte reaction (MLR). In addition, delayed-type hypersensitivity reaction (DTH) and skin allograft test in vivo were also carried out. Further, we have investigated the effect of glycyrol on phorbol 12-myristate 13-acetate (PMA)/ionomycin (Io)-stimulated IL-2 expression in Jurkat cells.

RESULTS:

The enzymatic assay showed glycyrol (IC(50) = 84.6 μM) inhibited calcineurin activity in a dose-dependent manner. Glycyrol, at the non-cytotoxic concentration, significantly inhibited proliferation of murine spleen T lymphocytes induced by Concanavalin A (Con A) and mixed lymphocyte reaction (MLR) in vitro. In addition, mice treated with glycyrol had shown the dose-dependent decrease in delayed type hypersensitivity (DTH) and prolonged the graft survival by 59% compared to the control group (*p < 0.05). RT-PCR showed glycyrol suppressed IL-2 production in a concentration-dependent manner.

DISCUSSION AND CONCLUSION:

Our results show the immunosuppressive activity of glycyrol and this activity should be due to its inhibitory effect on CN activity, thereby suppressing IL-2 production and regulating T lymphocytes. Thus, glycyrol could be a candidate for development as a novel immunomodulatory drug.

• Authors: Jiayu Li, Ying Tu, Li Tong, Wen Zhang, Jianquan Zheng, Qun Wei
• Journal: Pharmaceutical biology (Pharm Biol) Vol. 48 Issue 10 Pg. 1177-84 (Oct 2010) ISSN: 1744-5116 [Electronic] England
• PMID: 20860439 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcineurin Inhibitors
• EGR3 protein, human
• Flavonoids
• Immunosuppressive Agents
• Interleukin-2
• NFATC Transcription Factors
• Plant Extracts
• glycyrol
• Concanavalin A
• Early Growth Response Protein 3

Topics

• Animals
• Calcineurin Inhibitors
• Cell Proliferation (drug effects)
• Concanavalin A (immunology, pharmacology)
• Dose-Response Relationship, Drug
• Early Growth Response Protein 3 (immunology)
• Flavonoids (chemistry, pharmacology)
• Glycyrrhiza uralensis (chemistry)
• Graft Survival (drug effects, immunology)
• Humans
• Hypersensitivity, Delayed (immunology)
• Immunosuppressive Agents (chemistry, pharmacology)
• In Vitro Techniques
• Interleukin-2 (antagonists & inhibitors, biosynthesis)
• Jurkat Cells
• Lymphocyte Activation (drug effects)
• Lymphocyte Culture Test, Mixed
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• NFATC Transcription Factors (metabolism)
• Plant Extracts (chemistry, pharmacology)
• Plant Roots (chemistry)
• Signal Transduction (drug effects, physiology)
• Spleen (drug effects, immunology)
• T-Lymphocytes (drug effects, immunology)