Abstract

Three new 11-hydroxyburnamine (1) and rauvoyunnanines A–B (2–3), and fourteen known (4–17) monoterpenoid indole alkaloids were isolated from the total alkaloids extract of Rauvolfia yunnanensis, which exhibited promising immunosuppressive activity on T cell proliferation in preliminary screening. Their structures were determined by analysis of high-resolution electrospray ionization mass (HRESIMS), ultraviolet (UV) and nuclear magnetic resonance (NMR) data, and by comparison with the literature. All the alkaloids were evaluated for inhibitory activity on T cell proliferation. Among them, one new compound (1) and reserpine (6) exhibited moderate immunosuppressive activity, with IC50 values of 5.9 μM and 5.0 μM, respectively.

Highlights

  • Abnormal T cell proliferation plays a very important role in the development of T-cell mediated organ transplantation rejection and autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) [1,2]

  • Its UV spectrum showed absorption maxima at 207 and 293 nm, which is characteristic of a hydroindole/alkylaniline chromophore [18]

  • All isolated compounds were evaluated for the inhibitory activity against human T cell proliferation according to reported protocols [17]

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Summary

Introduction

Abnormal T cell proliferation plays a very important role in the development of T-cell mediated organ transplantation rejection and autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) [1,2]. Sirolimus and everolimus (Target-of-Rapamycin Inhibitors) inhibit nucleotide synthesis and azathioprine [5,6], and mycophenolic acid inhibits inosine monophosphate dehydrogenase and de novo GTP biosynthesis [7]. Their side effects, such as infections and toxicities, prompt scientists to look for new immunosuppressants constantly. Rauvolfia yunnanensis Tsiang (Apocynaceae) is a kind of shrub, mainly distributed in the south of China, such as Yunnan, Guizhou, and Guangxi Provinces. In our ongoing search for immunosuppressive compounds from medicinal plants [17], the total alkaloid extracts of whole R. yunnanensis plants exhibited promising immunosuppressive activity on T cell proliferation. The isolation, structural elucidation, and immunosuppressive activity of the isolated alkaloids are described

Identification of New Compounds
Immunosuppressive Activity Assay
General Experimental Procedures
Plant Material
T Cell Preparation
Cell Proliferation Assay
Statistical Analysis
Conclusions
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