Active ingredients of traditional Japanese (kampo) medicine, inchinkoto, in murine concanavalin A-induced hepatitis.
OBJECTIVE
The traditional Japanese (kampo) medicine inchinkoto (ICKT) is used in Eastern Asia as a choleretic and hepatoprotective agent. Previously, we reported that ICKT ameliorates murine concanavalin A (con A)-induced hepatitis via suppression of interferon (IFN)-gamma and interleukin (IL)-12 production. In the present study, we investigated the active ingredients of ICKT.


METHODS
ICKT and extracts of its component herbs were fractionated, and their effects on liver injury and cytokine production in vivo (biochemical markers of liver injury and cytokine levels in serum) and in vitro (cytokine and nitrite production in the cultures of splenocytes and peritoneal macrophages).


RESULTS
Decoctions of component herbs, Artemisiae Capillari Spica (Artemisia capillaris Thunberg: 'Inchinko' in Japanese), Gardeniae Fructus (Gardenia jasminoides Ellis: 'Sanshishi') and Rhei Rhizoma (Rheum palmatum Linné: 'Daio') were administered orally. Inchinko and Sanshishi decreased serum transaminases and IFN-gamma concentrations. Examination of fractions of component herbs suggested that capillarisin, a component of Inchinko, has potent hepatoprotective activity in vivo. In in vitro studies, capillarisin and genipin, an intestinal metabolite of geniposide that is contained in Sanshishi, were examined. IFN-gamma production was significantly suppressed by capillarisin and genipin in con A-stimulated splenocyte culture. Genipin also suppressed IL-1beta, IL-6, and IL-12p70 synthesis. Capillarisin and genipin decreased nitrite release from IFN-gamma-stimulated macrophages.


CONCLUSIONS
These results suggested that both Inchinko and Sanshishi may contribute to the protective effects of ICKT against con A hepatitis. Capillarisin was found to be potently hepatoprotective, and genipin may also contribute, especially via modulation of cytokine production.
Mase
Akihito
A
Tsumura Research Laboratories, Tsumura & Co., Ami, Ibaraki, Japan. mase akihito@mail.tsumura.co.jp
Makino
Bunsho
B
Tsuchiya
Naoko
N
Yamamoto
Masahiro
M
Kase
Yoshio
Y
Takeda
Shuuichi
S
Hasegawa
Takaaki
T
D000818:Animals; D019306:Artemisia / Q000737:chemistry; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D002867:Chromones / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D003208:Concanavalin A; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D032062:Gardenia / Q000737:chemistry; D006505:Hepatitis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood; D057889:Iridoid Glycosides; D039823:Iridoids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D019684:Magnoliopsida / Q000737:chemistry*; D008297:Male; D020835:Medicine, Kampo; D051379:Mice; D008807:Mice, Inbred BALB C; D009573:Nitrites / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012250:Rheum / Q000737:chemistry; D000637:Transaminases / Q000097:blood
D002867:Chromones; D016207:Cytokines; D057889:Iridoid Glycosides; D039823:Iridoids; D009573:Nitrites; D010936:Plant Extracts; D003208:Concanavalin A; C011185:capillarisin; D007371:Interferon-gamma; C007834:genipin; D000637:Transaminases