Periplocoside E, an effective compound from Periploca sepium Bge, inhibited T cell activation in vitro and in vivo.
Periploca sepium Bge, a traditional Chinese herb medicine, is used for treating rheumatoid arthritis in China. Followed the bioactivity-guided isolation, the most potent immunosuppressive compound, periplocoside E (PSE), a pregnane glycoside, had been identified from P. sepium Bge. We investigated the immunosuppressive effects of PSE in vitro and in vivo. The results showed that PSE in a dose-dependent manner significantly inhibited the proliferation of splenocytes induced by concanavalin A and mixed lymphocyte culture reaction at no cytotoxic concentrations (<5 microM). Administration of PSE suppressed a delayed-type hypersensitivity reaction, and ovalbumin (OVA) induced antigen-specific immune responses in mice. In vivo treatment with PSE dose dependently suppressed OVA-induced proliferation and cytokine [interleukin (IL)-2 and interferon (IFN)-gamma] production from splenocytes in vitro. Purified T cells from OVA-immunized mice with PSE treatment showed its low ability for activation by OVA plus normal antigen presenting cell stimulation again in vitro. Further studies showed PSE dose dependently inhibited anti-CD3-induced primary T cell proliferation, activation for IL-2Ralpha (CD25) expression, and cytokine (IFN-gamma and IL-2) production also at the transcriptional level. PSE was highly specific and significantly inhibited the activation of extracellular signal-regulated kinase and Jun N-terminal kinase, whereas activation of p38 was not affected in T cells stimulated with anti-CD3. These results demonstrated that PSE is an immunosuppressive compound in P. sepium Bge, which directly inhibits T cell activation in vitro and in vivo. This study provided evidence to understand the therapeutic effects of P. sepium Bge and indicated that this herb is appropriate for treatment of T cell-mediated disorders, such as autoimmune diseases.
Zhu
Yi-Na
YN
Laboratories of Immunopharmacology, Graduate School of the Chinese Academy of Sciences, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, People's Republic of China
Zhao
Wei-Min
WM
Yang
Yi-Fu
YF
Liu
Qun-Fang
QF
Zhou
Yu
Y
Tian
Jia
J
Ni
Jia
J
Fu
Yun-Feng
YF
Zhong
Xiang-Gen
XG
Tang
Wei
W
Zhou
Ru
R
He
Pei-Lan
PL
Li
Xiao-Yu
XY
Zuo
Jian-Ping
JP
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006968:Hypersensitivity, Delayed / Q000188:drug therapy* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D010047:Ovalbumin / Q000276:immunology; D031109:Periploca / Q000737:chemistry*; D024301:Plant Bark / Q000737:chemistry; D011283:Pregnenes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D016207:Cytokines; D004365:Drugs, Chinese Herbal; D007166:Immunosuppressive Agents; D009844:Oligosaccharides; D011283:Pregnenes; C509135:periplocoside E; D010047:Ovalbumin