New Immunosuppressive Sphingoid Base and Ceramide Analogues in Wild Cordyceps.

Jia-Ning Mi,Junping Kou,Zhi-Hong Jiang,Yingqiong Xu,Jing-Rong Wang,Yuwei Han

doi:10.1038/srep38641

Abstract

A comprehensive identification of sphingoid bases and ceramides in wild Cordyceps was performed by integrating a sequential chromatographic enrichment procedure and an UHPLC-ultrahigh definition-Q-TOF-MS based sphingolipidomic approach. A total of 43 sphingoid bases and 303 ceramides were identified from wild Cordyceps, including 12 new sphingoid base analogues and 159 new ceramide analogues based on high-resolution MS and MS/MS data, isotope distribution, matching with the comprehensive personal sphingolipid database, confirmation by sphingolipid standards and chromatographic retention time rule. The immunosuppressive bioassay results demonstrated that Cordyceps sphingoid base fraction exhibits more potent immunosuppressive activity than ceramide fraction, elucidating the immunosuppressive ingredients of wild Cordyceps. This study represented the most comprehensive identification of sphingoid bases and ceramides from a natural source. The findings of this study provided an insight into therapeutic application of wild Cordyceps.

Highlights

Regulating sphingolipid (SPL) metabolism is a promising strategy for immunomodulation1,2
We carried out a comprehensive identification of sphingoid bases and ceramides in wild Cordyceps by integrating a sequential chromatographic enrichment procedure and an improved sphingolipidomic approach established in our lab13,14
UHPLC-ultrahigh definition (UHD)-Q-TOF-MS was used to analyze Cordyceps sphingoid base and ceramide fractions which were prepared by using silica gel and amino silica gel column chromatographies (Supplementary Figure S1)

Summary

Introduction

Regulating sphingolipid (SPL) metabolism is a promising strategy for immunomodulation. Natural SPLs represent a classical and well-established source of chemical structure diversity for the development of new chemical entities with immunological effects. Natural SPLs represent a classical and well-established source of chemical structure diversity for the development of new chemical entities with immunological effects3,4 With these premises, global profiling of SPLs in herbal medicines provides a promising platform for the discovery and design of SPL-based immunomodulatory agents. N-(2′-hydroxy-tetracosanoyl)-2-amino-1,3,4-trihydroxy-octadec-8E-ene, a ceramide isolated from Cordyceps, has been reported to have immunomodulatory biological activity. N-(2′-hydroxy-tetracosanoyl)-2-amino-1,3,4-trihydroxy-octadec-8E-ene, a ceramide isolated from Cordyceps, has been reported to have immunomodulatory biological activity12 These evidence suggest that sphingoid bases and ceramides should be immunomodulatory active constituents of Cordyceps. The immunosuppressive activity of fractions of these sphingoid base and ceramide were assayed in lipopolysaccharide (LPS) and concanavalin A (Con A)-induced mouse splenic lymphocyte proliferation models

Objectives

Methods

Results

Conclusion