Periplocoside A, a pregnane glycoside from Periploca sepium Bge, prevents concanavalin A-induced mice hepatitis through inhibiting NKT-derived inflammatory cytokine productions.
Periploca sepium Bge, a traditional Chinese herb medicine, is widely used for treating rheumatoid arthritis in china. Periplocoside A (PSA), a pregnane glycoside, is a new nature product compound isolated from P. sepium Bge. We examined the protective effects of PSA, on concanavaline A (ConA)-induced hepatitis. Pretreatment with PSA dramatically ameliorated ConA-induced liver injury, which was characterized by reducing serum alanine transaminase (ALT), pathogenic cytokines of interleukin (IL)-4 and interferon (IFN)-gamma levels, impeding the liver necrosis, and thus elevating the survival rate. In vitro, PSA inhibited IL-4 and IFN-gamma productions of alpha-galactosylceramide (alpha-GalCer) or anti-CD3-activated Natural killer T (NKT) cells. Enzyme Linked Immunosorbent Assay (ELISA) and Reverse Transcription Polymerase Chain Reaction (RT-PCR) assays revealed PSA suppressed IL-4 transcription and IFN-gamma translation. In conclusion, PSA had significantly preventative effect on ConA-induced hepatitis, which was closely associated with inhibition of NKT-derived inflammatory cytokine productions. These findings suggested that PSA has the therapeutic potential for treatment of human autoimmune-related hepatitis.
Wan
Jin
J
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
Zhu
Yi-Na
YN
Feng
Jia-Quan
JQ
Chen
Hai-Jun
HJ
Zhang
Ru-Jun
RJ
Ni
Jia
J
Chen
Zhen-Hua
ZH
Hou
Li-Fei
LF
Liu
Quan-Fang
QF
Zhang
Jing
J
Yang
Li
L
Tang
Wei
W
Yang
Yi-Fu
YF
Nan
Fa-Jun
FJ
Zhao
Wei-Ming
WM
Zuo
Jian-Ping
JP
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017252:CD3 Complex / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000517:prevention & control*; D003208:Concanavalin A / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis* / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000494:pharmacology; D006027:Glycosides / Q000494:pharmacology*; D007202:Indicators and Reagents; D007694:Killer Cells, Natural / Q000378:metabolism*; D008111:Liver Function Tests; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009844:Oligosaccharides / Q000494:pharmacology; D031109:Periploca / Q000737:chemistry*; D011283:Pregnenes / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D017252:CD3 Complex; D016207:Cytokines; D005699:Galactosylceramides; D006027:Glycosides; D007202:Indicators and Reagents; D009844:Oligosaccharides; D011283:Pregnenes; C493154:alpha-galactosylceramide; C509135:periplocoside E; D003208:Concanavalin A; C056990:periplocoside A; D000410:Alanine Transaminase