periplocoside-e and Chemical-and-Drug-Induced-Liver-Injury

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.

Topics: Alanine Transaminase; Animals; Antineoplastic Agents, Phytogenic; CD3 Complex; Cell Proliferation; Cell Separation; Cell Survival; Chemical and Drug Induced Liver Injury; Concanavalin A; Cytokines; Female; Flow Cytometry; Galactosylceramides; Glycosides; Indicators and Reagents; Killer Cells, Natural; Liver Function Tests; Lymphocyte Culture Test, Mixed; Lymphocytes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Monocytes; Oligosaccharides; Periploca; Pregnenes