Immunosuppressive constituents from Urtica dentata Hand.
A novel biscoumarin, 6,6',7,7'-tetramethoxyl-8,8'-biscoumarin (1), was isolated from the ethyl acetate extract of Urtica dentata Hand, together with five known compounds named as 7,7'-dihydroxy-6,6'-dimethoxy-8,8'-biscoumarin (2), 7,7'-dimethoxy-6,6'-biscoumarin (3), scoparone (4), vanillic acid (5), and daucosterol (6). Structures of the isolated compounds were elucidated on the basis of spectroscopic analysis including 2D NMR experiments. Compounds 1 and 2 were confirmed to be a rare carbon-carbon linked symmetrical biscoumarin. Compounds 1-4, especially 1 (IC(50) = 8.18 x 10(- 5) mol/l), showed potent immunosuppressive activities as determined by the Cell Counting Kit-8 assay for lymphocyte proliferation. Also, in the FACS analysis, 1 (IC(50) = 5.19 x 10(- 4) mol/l) promoted the differentiation of CD4(+)CD25(+)Foxp3(+) T regulatory cells distinctly compared to the normal control. Thus, 1 possessed specific immunosuppressive property by eliciting T regulatory cells, which may provide a potential treatment strategy for autoimmune diseases.
Hou
Wen-Rui
WR
Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Su
Zhi-Qiang
ZQ
Pi
Hui-Fang
HF
Yao
Guang-Min
GM
Zhang
Peng
P
Luo
Xiang
X
Xie
Sheng-Nan
SN
Xiang
Ming
M
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D027003:Urticaceae / Q000737:chemistry*
C552008:6,6',7,7'-tetramethoxyl-8,8'-biscoumarin; D015704:CD4 Antigens; D003374:Coumarins; D004365:Drugs, Chinese Herbal; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit