Clinical and Pharmacological Studies on Liver Diseases Treated with Kampo Herbal Medicine

American Journal of Chinese Medicine, Summer-Fall, 2000 by Jong-Chol Cyong, Sun-Min Kim, Koji Iijima, Takao Kobayashi, Minoru Furuya

Abstracts: Hepatitis C virus (HCV) infection frequently causes chronic hepatitis, which is linked to the development of liver cirrhosis and hepatocellular carcinoma. Most physicians who practice Kampo medicine in Japan have observed that Kampo medicine can be as effective as interferon therapy in the treatment of chronic hepatitis C. In the present study, to evaluate the effect of Kampo medicine on chronic hepatitis C, clinical treatment was assessed in short-term and long-term study, and it was shown that Ninjin-yoei-to (Formula ginseng compositae: TJ-108) was very effective. Therefore, to find the most active herbal component of TJ-108 in the treatment of HCV, Citrus Unshiu Peel, Schisandra Fruit, and Polygala Root, which are specific to TJ-108, were screened using an in vitro HCV infection model. Among the three herbs, Schisandra Fruit was found to be most active. In the next step, Gomisin A, an active component of Schisandra Fruit, was studied using an in vitro model with MOLT-4 cells and an animal model of immunologically induced acute hepatic failures. It is concluded that the therapeutic effect of TJ-108 on chronic hepatitis C is from the inhibitory effect on HCV infection, and also from the protective effect on immunological hepatopathy of Schisandra Fruit and its lignan component, Gomisin A.

More than 170 million people are infected by Hepatitis C virus (HCV) world wide. While interferon is currently the most used single agent therapy, it is reported that interferon is successful in only up to 15% of patients in getting rid of the virus (Gish, 1999). A new effective therapeutic option is expected to be developed for treating HCV. Patients with chronic hepatitis C usually complain of systemic weakness, fatigue and loss of appetite (Luo et al., 1998). Most physicians who practice Kampo medicine have observed that Kampo medicine can easily improve these symptoms (Tajiri et al., 1991). We investigated the clinical effect of Kampo medicine on the course of chronic hepatitis C. In Asian countries, the Schisandra Fruit has traditionally been used for hepatitis and bronchitis. Gomisin A, a lignan component of Schisandra Fruit, has been reported to have hepatoprotective effect (Nomura et al., 1994; Shiota et al., 1996). We have found that Gomisin A has anti-viral-adhesion effect and anti-hepatitis effect, which were screened by using an in vitro model with MOLT-4 (human lymphoblastoma) and an animal model of immunologically induced acute hepatic failures (Arai et al., 1995).

Materials and Methods

Herbal Preparations and Isolation of Active Substances

Ninjin-yoei-to (Formula ginseng compositae: TJ-108), Juzen-taiho-to (Formula decem supplementrum major: TJ-48) and Dai-saiko-to (Formula bupleuri major: TJ-8) (Table 1) were obtained from Tumura Pharmaceutical Company (Tokyo, Japan) as commercial products.

Table 1. Composition of Ninjin-yoei-to, Juzen-taiho-to and Dai-saiko-to

                               Ninjin-yoie-to               TJ- 108

9.0 g (one day dosage) contains 6.0 g of dried extract obtained
from mixed raw herbs in the following ratio:
                               Rehmannia Root               4.0g
                               Japanese Angelica Root       4.0g
                               Atractylodes Rhizome         4.0g
                               Hoelen                       4.0g
                               Ginseng Root                 3.0g
                               Cinnamon Bark                2.5g
                               Polygala Root                2.0g
                               Peony Root                   2.0g
                               Citrus Unshiu Peel           2.0g
                               Astragalus Root              1.5g
                               Glycyrrhiza Root             1.0g
                               Schisandra Fruit             1.0g

                               Juzen-taiho-to               TJ-48

7.5g (one day dosage) contains 5.0g of dried extract obtained from
mixed raw herbs in the following ratio:
                               Astragalus Root              3.05g
                               Cinnamon Bark                2.5g
                               Rehmannia Root               4.0g
                               Peony Root                   2.0g
                               Cnidium Rhizome              3.0g
                               Atractylodes Lancea Rhizome  3.0g
                               Japanese Angelica Root       3.0g
                               Ginseng Root                 3.0g
                               Hoelen                       3.0g
                               Glycyrrhiza Root             1.5g

                               Dai-saiko-to                 TJ-8

7.5g (one day dosage) contains 4.5g of dried extract obtained from
mixed raw herbs in the following ratio:
                               Bupleurum Root               6.0g
                               Pinellia Tuber               4.0g
                               Scutellaria Root             3.0g
                               Peony Root                   3.0g
                               Jujube Root                  3.0g
                               Immature Orange              2.0g
                               Ginger Rhizome               1.0g
                               Rhubarb Rhizome              1.0g