-IBIS-1.7.0-
tx
digestive system
hepatitis
Chinese Formulae

formulas

» acute:

Ji Gu Cao Wan (Abrus pectoralis): reported to cure chronic Hepatitis B.

Gentiana C. (Long Dan Xie Gan Wan) (available as patent); Gentiana 12: Liver and Gall Bladder Invaded by Damp-Heat (Gentiana C.: Hsu, 1980, p. 181; Yeung, p. 154; Dharmananda, 1986, p. 229; Bensky and Barolet, p. 96; patent: Zhu, p. 172; Gentiana 12: Dharmananda, 1990, p. 69)

Capillaris C. (Yin Chen Hao Tang); Shi Lin Tong Pian (patent): Damp-Heat Jaundice (Capillaris C.: Hsu, 1980, p. 519; Yeung, p. 273; Dharmananda, 1986, p. 304; Bensky and Barolet, p. 189; Shi Lin: Zhu, p. 212)

Bupleurum, Cinnamon and Ginger C. (Chai Hu Gui Zhi Gan Jiang Tang); Ji Gu Cao Wan (patent) plus Li Gan Pian (patent): Liver Fire Blazing Upward: fever, sweating, thirst (Bupleurum: Hsu, 1980, p. 85; Bensky and Barolet, p. 138; Ji Gu Cao Wan: Zhu, p. 195; Li Gan Pian: Fratkin, p. 97)

• Major Bupleurum C. (Da Chai Hu Tang) plus gardenia (zhi zi) and phellodendron (huang bai): alternating fever and chills, bitter taste in the mouth, nausea, continuous vomiting, burning diarrhea or no bowel movements, despondency, irritability, yellow tongue coat, wiry pulse

(Hsu, 1980, p. 128; Yeung, p. 61; Dharmananda, 1986, p. 154; Bensky and Barolet, p. 139)

• Bupleurum 12 (patent) plus Isatis 6 (patent) (Dharmananda, 1990: Bupleurum, p. 39: Isatis, p. 71)

Minor Bupleurum Decoction (xiao-chai-hu-tang or sho-saiko-to): a formula commonly used for Hepatitis B in Japan; Bupleurum alone contraindicated in Yin Xu (Deficiency) conditions (Yamashiki M, et al. J Clin Lab Immunol. 1992; 37(3): 111-121; Yamashiki M, et al. Hepatology 1997 Jun;25(6):1390-1397.)

» chronic:

Bupleurum/Gardenia Formula (bupleurum 15%, peony 15% (5% each of peony, red peony, moutan), gardenia 15%, forsythia 15%, astragalus 15%, salvia 15%, tang-kuei 10%): for cases involving more severe viral hepatitis involving both Xue Ye (Blood Stasis) and damp-heat (but not those of Liver/Kidney Yin Xu (Deficiency) or Spleen/Stomach Xu (Deficiency) (Dharmananda, S.)

Bupleurum and Schizonepeta Comb.; Li Gan Pian (patent): Heat.

(Bupleurum and Schizonepeta: Hsu, 1980, p. 624; Li Gan Pian: Zhu, p. 180)

Capillaris C. (Yin Chen Hao Tang); Ji Gu Cao Wan (patent): Damp-Heat: acute or chronic hepatitis with jaundice (Capillaris: Hsu, 1980, p. 519; Yeung, p. 273; Dharmananda, 1986, p. 304; Bensky and Barolet, p. 189; Ji Gu Cao: Zhu, p. 195)

Eclipta Tablets (patent) with Liver/Kidney Yin Xu (Deficiency) complicated by Stomach/Spleen Xu (Deficiency) (Dharmananda, S.)

Shi Gu Wan (patent): Liver Qi Stagnation (Zhu, p. 215)

Linking Decoction (Yi Guan Jian) (add schizandra (wu wei zi) in well patients with elevated liver enzymes): Liver Yin Xu (Deficiency) with Liver Qi Stagnation

(Yeung, p. 271; Bensky and Barolet, p. 271)

Qing Tui Fang: salvia 30 g [vitalize blood and remove heat], red peony 30 g, crataegus 15 g, moutan 15 g, forsythia 30 g [clean toxin, remove damp-heat], gardenia 15 g, dandelion 15 g, ho-shou-wu 15 g [nourish yin and blood], astragalus 30 g [tonify qi to dispel the pathogen], bupleurum 10 g [regulate qi]; decocted and taken in two divided doses each day. (Li Hougen, et al, Chinese Journal of Integrated Traditional and Western Medicine for Liver Diseases (5) 1994; 4(2): 40.)

Salvia Ligustrum (patent): used for Hepatitis B, also used with Hepatitis C

• Shu Gan Li Pi Tang: Liver Qi Xu (Deficiency) with Spleen Qi Xu (Deficiency): intense hypochondriac pain, irritability, insomnia, fatigue, reduced appetite, loose stools, chronic hepatitis (Bensky and Barolet, p. 149)

• Wuchi Pai Feng Wan (patent): Xue Xu (Blood Deficiency) with Qi Xu (Deficiency) (Zhu, p. 247)

• He Che Da Zao Wan (patent): Weakness due to Yin Xu (Deficiency) (Zhu, p. 286)

• Tang Kuei 18 (patent): Xue Xu (Blood Deficiency) and Yin Xu (Deficiency) (Dharmananda, 1990, p. 26)

» key herbs:

• bai hua (Oldenlandia tenelliflora)

• ban zhi lian (Scutellaria barbata): clear Toxin herb, especially with Liver Heat

• chuan lian zi (Meliae toosendan): for liver pain due to hepatitis

• da huang (Rhizoma rhei - rhubarb): very effective for Xue Ye (Blood Stasis), especially constipation (Zhou Z. Chung Kuo Chung Yao Tsa Chih 1989 Aug;14(8):501-3, 512.)

• dan lan gen (Isatis tinctoris)

• gan cao (Glycyrrhiza) (Abe, Y, Ueda, I, Kato, T, et al. Nippon Rinsho 1994;52:1817-1822; Sato H, et al. Antiviral Res 1996 May;30(2-3):171-177. )

• huang qin (Scutellaria baicalensis)

• ku shen (Sophora flavescentus): especially with Damp Heat; active ingredient thought to be matrine and oxymatrine

• pu gong ying (Taraxaci mongolicae): especially with jaundice

• wu wei zi (Fructus Schizandrae): for Yin Xu (Deficiency), especially with sleep disorders; may be used alone (Liu GT. Chin Med J (Engl) 1989 Oct;102(10):740-749.)

• yin chen hao (Artemesia capillaris): especially with jaundice

• yu jin (Curcumae)

• zhi zi (Gardenia jasminoidis)

» interactions:

Bupleurum (Chai Hu) and Interferon: There are several reports of Bupleurum, within the context of Minor Bupleurum Decoction (xiao-chai-hu-tang or sho-saiko-to), causing lung damage when combined with interferon. (See Interferon as an Interactions topic in the Integrative Therapies Materia Medica)

» research:

Subhuti Dharmananda, Ph.D. has summarized the three key points presented by Chen Lihua concerning the traditional Chinese medical analysis of hepatitis C characteristics and corresponding treatments:

1. Toxic pathogens directly enter the nutritive (ying) and blood (xue) levels: most people are infected via blood or plasma transfusion, and the respective pathogen therefore immediately enters the nutritive layer (rather than slowly making its way through the outer defensive layers of the body). The clinical symptom picture seems to support this traditional way of reasoning, since patients usually exhibit little or no symptoms of disease entering the qi level (typically manifesting in fever, jaundice, and digestive symptoms). In response, one should vitalize the blood and resolve toxin: the author suggests the use of herbs that can both move blood and resolve toxin, such as lithospermum, hu-chang, moutan, red peony, rhubarb, curcuma, and oldenlandia.

2. Toxic stasis accumulates easily, smolders chronically, and is hard to disperse: hepatitis C is different from other types of liver disease in that it does not manifest like a warm disease. Although the pathogen directly enters the blood, there are usually no symptoms of rashes, red tongue, bleeding, loss of consciousness, etc. On the contrary, it can be classified as a yin type disease, a damp toxin, which causes damp stagnation, yin coagulation, toxic accumulation, clogging of the collaterals, and obstruction of yang. In response, one should disperse the liver qi and transform phlegm. Due to the characteristics of toxin, blood stasis, phlegm, and dampness, there is usually a chronic disease process that does not respond well to treatment. The author recommends qi-regulating herbs, such as bupleurum, blue citrus, citrus, cyperus, magnolia bark as well as phlegm-transforming herbs such as kelp, laminaria, fritillaria, pinellia.

3. Kidney deficiency promotes infection, and middle aged and old people are primarily afflicted. Since the distinguishing factor of older people is their declining kidney qi, kidney qi weakness seems to have something to do with being prone to the development (worsening) of the disease. [note: this characteristic of affecting older people is mainly due to the long duration of viral quiescence or slow disease progress before significant liver disease causes one to seek medical testing and treatment. However, the situation is changing: diagnosis is being made earlier; still, it is currently rare to receive a diagnosis of hepatitis C prior to age 40]. In older patients, one should tonify the liver and kidney: since there usually are more symptoms of kidney qi deficiency and kidney yang deficiency involved, some of the following herbs should be added in moderate amounts: morinda, epimedium, curculigo, cuscuta, and fenugreek. At the same time some yin tonics should be added to prevent a overheating effect by the yang tonics, such as rehmannia, lycium fruit, and ho-shou-wu.

(Chen Lihua, J Trad Chin Med 1994; (10). )

In a study reported in the 1998 Journal of Traditional Chinese Medicine by in Shi and Wang Yue, 108 patients with hepatitis C were analyzed according to TCM. These patients had not used interferon (or had not had drug treatment for at least 6 months) or Chinese herbs (or had not had herbal treatment for at least 3 months). The proportion of males and females was relatively equal: 65 were male, 43 female, with an age range of 22–71 (average age 55). The high average age of this group, and the relatively more equal distribution among males and females correlates well with the proposal that the main risk factor is blood transfusion rather than "socializing." The patients were then evaluated and assigned into the five categories listed above, revealing:

34 had blood stasis

16 had damp-heat

16 had liver/kidney yin deficiency

12 had spleen/kidney yang deficiency

9 had liver qi stagnation with spleen deficiency

21 were difficult to categorize

Those with a diagnosis of damp-heat had highly-elevated liver enzymes, while those in the other diagnostic categories only had moderate elevation. The authors believe that it is likely that the symptoms generated by severe liver inflammation (abdominal bloating, nausea, loss of appetite, yellowing of eyes and skin) fit the damp-heat category. The high incidence of blood-stasis was described by the authors as a possible outcome of the tendency of hepatitis C to cause liver cirrhosis. This condition leads to hardening of the liver (and, sometimes the spleen) and partial blockage of the portal vein. This group had a moderate proportion of cases of spleen/kidney yang deficiency, as might be expected with patients having an average age of 55.

(Jin Shi and Wang Yue, J Trad Chin Med 1998; 39(4): 233–235.)

Article abstracted by Subhuti Dharmanada, Ph.D. of Institute of Traditional Medicine

In a study reported in the 1998 Journal of Traditional Chinese Medicine (4), 108 patients with hepatitis C were analyzed according to TCM. These patients had not used interferon (or had not had drug treatment for at least 6 months) or Chinese herbs (or had not had herbal treatment for at least 3 months). The proportion of males and females was relatively equal: 65 were male, 43 female, with an age range of 22–71 (average age 55). The high average age of this group, and the relatively more equal distribution among males and females correlates well with the proposal that the main risk factor is blood transfusion rather than "socializing." The patients were then evaluated and assigned into the five categories listed above, revealing:

34 had blood stasis

16 had damp-heat

16 had liver/kidney yin deficiency

12 had spleen/kidney yang deficiency

9 had liver qi stagnation with spleen deficiency

21 were difficult to categorize

Those with a diagnosis of damp-heat had highly-elevated liver enzymes, while those in the other diagnostic categories only had moderate elevation. The authors believe that it is likely that the symptoms generated by severe liver inflammation (abdominal bloating, nausea, loss of appetite, yellowing of eyes and skin) fit the damp-heat category. The high incidence of blood-stasis was described by the authors as a possible outcome of the tendency of hepatitis C to cause liver cirrhosis. This condition leads to hardening of the liver (and, sometimes the spleen) and partial blockage of the portal vein. This group had a moderate proportion of cases of spleen/kidney yang deficiency, as might be expected with patients having an average age of 55.

(Jin Shi and Wang Yue, J Trad Chin Med 1998; 39(4): 233–235.) Article abstracted by Subhuti Dharmanada, Ph.D. of Institute of Traditional Medicine

Comparing hepatitis B and C, Hong Huiwen and his colleagues (3) examined 100 chronic hepatitis B patients and 50 chronic hepatitis C patients. As noted previously, the patients with hepatitis B tend to be younger than those with hepatitis C (32.7

vs. 46.1 years, mean values in this study). These authors thought that hepatitis B tended to be transmitted more with "socializing"—-indulgence in illicit injected drugs and unsafe sexual activity, among other things—which not only accounts for the younger age, but also the tendency for it to affect males (in their group, 89 males and 11 females had hepatitis B; in China it is primarily young men who partake in high-risk "socializing"). Getting a blood transfusion due to diseases of old age was thought to be the reason that hepatitis C tended to involve older individuals and have less sexual differentiation in incidence rates (35 males, 15 females in the hepatitis C group). As to the categories of disorder:

Hepatitis B Hepatitis C

Damp-heat 41% 26%

Blood stasis 1% 12%

Liver and kidney yin deficiency 15% 8%

Liver qi stagnation with spleen qi deficiency 42% 54%

Spleen and kidney yang deficiency 1% 0%

These findings tend to confirm the previous report, which was that there were similarities in frequency of liver and kidney yin deficiency, liver qi stagnation, and spleen/kidney deficiency between the two groups, but that there was more damp-heat with hepatitis B and more blood stasis with hepatitis C. The authors also presented information on the tongue and pulse qualities. Generally, patients with hepatitis B tended to have a pale or dark tongue and a yellow greasy coating and a fine wiry pulse or a wiry slippery pulse; patients with hepatitis C tended to have a dark or dark purple tongue, with a thin white coating, and a fine wiry pulse. These findings lend further support to the contended differentiation into damp-heat and blood stasis categories for hepatitis B and C, respectively.

(Hong Huiwen, et al., J Trad Chin Med 1997; 38(12): 732–734.) Article abstracted by Subhuti Dharmanada, Ph.D. of Institute of Traditional Medicine

In a study of integrated Chinese and Western medical treatment, 64 patients who had a history of blood transfusion and who tested positive for hepatitis C were divided into two groups of 32 patients each. The control group received alpha-interferon and the herb group received alpha-interferon plus herbal decoctions (depending on presenting symptoms and signs); each was treated for three months. As an example, for those classified as presenting liver-qi stagnation and spleen deficiency, the formula has 15 grams bupleurum, 12 grams hoelen, 10 grams atractylodes, 10 grams codonopsis, 10 grams peony, 6 grams chih-ko, 6 grams gardenia, 6 grams curcuma, and 5 grams licorice. For those classified as having accumulated heat toxin, the formula was 15 grams lithospermum, 15 grams hu-chang, 15 grams forsythia, 12 grams scrophularia, 12 grams gardenia, 10 grams raw rehmannia, 10 grams moutan, 10 grams red peony, 6 grams curcuma, and 5 grams licorice. Other herbs might be added to these base formulas for treating specific symptoms. Among the 32 persons treated by herbs, 4 had their antibody tests turn negative, compared to only 2 in the interferon only group. Of the others, 17 in the herb group had major symptoms eliminated and ALT normalized, while 13 in the interferon group attained these results. It appeared that the use of Chinese herbs enhanced the effects of interferon treatment.

(Lu Jiawu. Chinese Journal of Integrated Traditional and Western Medicine 1995;15(6): 371.) Article abstracted by Subhuti Dharmanada, Ph.D. of Institute of Traditional Medicine

In a report of the Hunan Journal of Traditional Chinese Medicine by Deng Desheng, the results of applying Song Zhi Mixture #2 to 30 patients was described. The mixture is said to contain hoelen, gardenia, pseudostellaria, hypericum, and other undisclosed ingredients. These ingredients were apparently made into an extract that was taken one bag each time, three times daily for three months. The researchers used liver enzymes and antibody testing to evaluate the results. A total of 30 patients were tested, some with acute hepatitis C, others with chronic hepatitis C, the latter group further divided into those with or without accompanying hepatitis B. The rate of turning the antibody test from positive to negative was high. For example, among 12 patients who had chronic hepatitis C (without hepatitis B), 10 became negative; liver enzyme levels normalized for all but one of the patients.

(Deng Desheng, Hunan Journal of Traditional Chinese Medicine 1997; 13(6): 27–28.)

Article abstracted by Subhuti Dharmanada, Ph.D. of Institute of Traditional Medicine

footnotes

Abe, Y, Ueda, I, Kato, T, et al. Effectiveness of interferon, glycyrrhizin combination therapy in patients with chronic hepatitis C. Nippon Rinsho 1994;52:1817-1822 . [Article in Japanese]

Chen HC, Chou CK, Kuo YH, Yeh SF. Identification of a protein kinase C (PKC) activator, daphnoretin, that suppresses hepatitis B virus gene expression in human hepatoma cells. Biochem Pharmacol 1996 Oct 11;52(7):1025-1032.

Abstract: We examined the antiviral activity of a crude extract prepared from a Chinese medicinal herb Wikstroemia indica C.A. Mey. One active component, daphnoretin (7-hydroxyl-6-methoxy-3,7'-dicoumarylether), was identified, which showed strong suppressive effects on the expression of the hepatitis B surface antigen (HBsAg) in human hepatoma Hep3B cells. To examine the signaling pathway of daphnoretin on the Hep3B cells, we pretreated Hep3B cells with 12-O-tetradecanoylphorbol-13-O-acetate (200 nM) for 24 hr to down-regulate intracellular protein kinase C (PKC) levels and found that the PKC-down-regulated Hep3B cells did not respond at all to daphnoretin. Furthermore, daphnoretin induced translocation of PKC from the cytosol to the membrane and down-regulated intracellular PKC levels in the Hep3B cells, indicating that it may directly activate PKC. This hypothesis was supported by the observation that daphnoretin directly competed with [3H]phorbol dibutyrate for the binding of PKC in the whole cell and activated purified PKC activity in vitro. Our results demonstrated that daphnoretin, with a structure distinct from phorbol ester, is a PKC activator and has suppressive effects on HBsAg gene expression in human hepatoma cells.

Chen Lihua, Hepatitis C: Characteristics and TCM treatment methods, J Trad Chin Med 1994; (10).

Deng Desheng, 30 cases of hepatitis C treated with Song Zhi Mixture, Hunan Journal of Traditional Chinese Medicine 1997; 13(6): 27–28.

Dharmananda, Subhuti. Hepatitis C: Recent Treatment Strategies. Institute for Traditional Medicine, Portland, OR. www.europa.com/~itm/hepcnew.htm

Fujisawa, K. Interferon therapy in hepatitis C virus (HCV) induced chronic hepatitis: Clinical significance of pretreatment with glycyrhizine. Trop Gastroenterol 1991;12:176-179.

Hong Huiwen, et al., Analysis of clinical and therapeutic specificity in treating chronic hepatitis B and C, J Trad Chin Med 1997; 38(12): 732–734.

Jin Shi and Chen Quanliang, Clinical manifestations of hepatitis C and hepatitis B: A comparative approach utilizing TCM differential diagnostics, J Trad Chin Med 1994; (9).

Jin Shi and Wang Yue, Probing into the relationship between the TCM differentiations of chronic hepatitis C and clinical determination results, J Trad Chin Med 1998; 39(4): 233–235.

Kakumu S, et al. Effects of TJ-9 Sho-saiko-to (kampo medicine) on interferon gamma and antibody production specific for hepatitis B virus antigen in patients with type B chronic hepatitis. Int J Immunopharmacol. 1991; 13(2-3): 141-146.

Li Hougen, et al., Qingtui Fang applied in treating 128 cases of chronic hepatitis C, Chinese Journal of Integrated Traditional and Western Medicine for Liver Diseases (5) 1994; 4(2): 40.

Li Jiqiang, et al., A preliminary study on therapeutic effect of oxymatrine in treating patients with chronic hepatitis C, Chinese Journal of Integrated Traditional and Western Medicine, 1998; 18(4): 227–229.

Lin SC, Lin CC, Lin YH, Shyuu SJ. Hepatoprotective effects of Taiwan folk medicine: wedelia chinensis on three hepatotoxin-induced hepatotoxicity. Am J Chin Med 1994;22(2):155-168.

Abstract: The hepatoprotective effects of a Taiwanese crude herb, Hwang-hua-mih-tsay (Wedelia chinensis (Osbeck) Merr.), were investigated. Acute hepatitis was induced by three hepatotoxins: carbon tetrachloride and acetaminophen in mice, and D(+)-galactosamine in rats. After treatment with W. chinensis (300 mg/kg, p.o.) at 2, 6 and 10 hours, a reduction in the elevation of serum glutamate oxaloacetic transaminase (SGOT) and glutamate pyruvic transaminase (SGPT) levels was observed at 24 hrs after hepatotoxins were administered. These serological observations were confirmed by histopathological examinations. A microscopic examination of the liver showed a marked improvement in groups receiving W. chinensis. In order to further confirm the hepatoprotective effect of W. chinensis, all pharmacological and histopathological effects were compared with Bupleurum chinense DC. (family Umbelliferae), a well documented antihepatotoxicity herb. It was concluded that W. chinensis has a definite hepatoprotective effect against liver injuries.

Lin SC, Lin CC, Lin YH, Yao CJ. Hepatoprotective effects of Taiwan folk medicine: Ixeris chinensis (Thunb.) Nak. on experimental liver injuries. Am J Chin Med 1994;22(3-4):243-254.

Abstract: The hepatoprotective effects of Ixeris chinensis (Thunb.) Nak. were studied on acute hepatitis induced in mice by a single dose of carbon tetrachloride (31.25 microliters/kg, ip) or acetaminophen (600 mg/kg, ip), and in rats by a single dose of beta-D-galactosamine (188 mg/kg, ip). Hepatoprotective activity was monitored by estimating the serum transaminases (SGOT and SGPT) levels and histopathological changes in the livers of experimental animals. The Ixeris chinensis (Thunb.) Nak. extracts significantly inhibited the acute elevation of serum transaminases. Histopathologically, the crude I. chinensis extract significantly ameliorated hepatotoxin-induced histopathological changes in the livers of experimental animals. All pharmacological and histopathological effects of Ixeris chinensis (Thunb.) Nak. were compared with Bupleurum chinense DC., which has been previously reported as a treatment herb for hepatitis.

Liu GT. Pharmacological actions and clinical use of fructus schizandrae. Chin Med J (Engl) 1989 Oct;102(10):740-749.

Abstract: Fructus Schizandrae (FS) is a well-known Chinese herb which has been widely used in ancient China. During recent decades, it has been found to be effective in viral and chemical induced hepatitis. In this paper, we report the studies on the chemical constituents and pharmacological actions of FS on mice liver. The results indicated that FS and its several components can mainly protect liver from injury induced by toxic substances such as CCl4; they have anti-oxidant activities against oxygen free radicals; FS and four components have inducing action on liver cytochrome P-450; they also promote certain anabolic metabolism such as serum protein biosynthesis and glycogenesis. All these activities would be of importance in the protection and repair of the injured liver cells. The clinical use of FS is also presented.

Liu Qingchi, et al., Clinical study of Traditional Chinese Medicine and Western medicine on aplastic anemia complicated with hepatitis C, Chinese Journal of Traditional and Western Medicine 1995; 15(4): 198–201.

Lu Jiawu, 32 chronic hepatitis C patients treated by integrating Chinese herbs and interferon, Chinese Journal of Integrated Traditional and Western Medicine 1995;15(6): 371.

Nakagawa, A, Yamaguchi, T, Takao, T, Amano, H. Five cases of drug-induced pneumonitis due to sho-saiko-to or interferon alpha or both. Nippon Kyobu Gakkai Zasshi 1995 Dec;33:1361-1366 . [Article in Japanese]

Sato H, Goto W, Yamamura J, Kurokawa M, Kageyama S, Takahara T, Watanabe A,

Shiraki K. Therapeutic basis of glycyrrhizin on chronic hepatitis B. Antiviral Res 1996 May;30(2-3):171-177.

Abstract: Glycyrrhizin, a major component of a herb (licorice), has been intravenously used for the treatment of chronic hepatitis B in Japan and improves liver function with occasional complete recovery from hepatitis. This substance modifies the intracellular transport and suppresses sialylation of hepatitis B virus (HBV) surface antigen (HBsAg) in vitro. This study was designed to clarify the pharmacological basis for its effectiveness. The structure-bioactivity relationship of glycyrrhizin, glycyrrhetic acid 3-O-monoglucuronide and glycyrrhetic acid was determined, and glycyrrhetic acid was found to be the most active of them. The amounts of three substances bound to the liver were evaluated in guinea pig after intravenous administration of glycyrrhizin. Glycyrrhizin and glycyrrhetic acid 3-O-monoglucuronide were detected at concentrations of 31.8-1.3 micrograms/g of liver, but glycyrrhetic acid was not detected. When glycyrrhizin attained these concentrations in the cellular fraction of the PLC/PRF/5 cell culture, it suppressed the secretion of HBsAg as reported previously. These results indicated that glycyrrhizin administered intravenously might bind to hepatocytes at the concentration at which glycyrrhizin could modify the expression of HBV-related antigens on the hepatocytes and suppress sialylation of HBsAg.

Sugiyama, H, Nagai, M, Kotajima, F, Yoshizawa, A, Kamimura, M, Horiuchi T, Kudo K, Kabe J, Hayashi, S, Umeda, N. A case of interstitial pneumonia with chronic hepatitis C following interferon-alfa and sho-saiko-to therapy. Arerugi 1995 Jul;44(7):711-714 [Article in Japanese]

Takahara T, Watanabe A, Shiraki K. Effects of glycyrrhizin on hepatitis B surface antigen: a biochemical and morphological study. J Hepatol 1994 Oct;21(4):601-609.

Abstract: Glycyrrhizin, a major component of a herb (licorice), has been widely used to treat chronic hepatitis B in Japan. This substance improves liver function with occasional complete recovery from hepatitis; its effects on the secretion of hepatitis B surface antigen (HBsAg) were examined in vitro. Glycyrrhizin suppressed the secretion of HBsAg and accumulated it dose-dependently in PLC/PRF/5 cells. Its action was further analyzed and determined in the HBsAg-expression system using the varicella-zoster virus. Glycyrrhizin suppressed the secretion of HBsAg, resulting in its accumulation in the cytoplasmic vacuoles in the Golgi apparatus area. HBsAg labeled with 35S-methionine and cysteine accumulated in the cells and its secretion was suppressed dose-dependently in glycyrrhizin-treated culture. The secreted HBsAg was modified by N-linked and O-linked glycans but its sialylation was inhibited dose-dependently by glycyrrhizin. Thus glycyrrhizin suppressed the intracellular transport of HBsAg at the trans-Golgi area after O-linked glycosylation and before its sialylation. HBsAg particles were mainly observed on the cell surface in the glycyrrhizin-treated culture but not in the untreated culture. This suggests that asialylation of HBsAg particles resulted in the novel surface nature of glycyrrhizin-treated HBsAg particles. We elucidated the unique mechanism of action of glycyrrhizin on HBsAg processing, intracellular transport, and secretion.

Wang M, Cheng H, Li Y, Meng L, Zhao G, Mai K. Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: observations with three preparations from different geographic sites. J Lab Clin Med 1995 Oct;126(4):350-352.

Abstract: It has been suggested that herbs of the Phyllanthus family may have antiviral activity. We therefore tested the effects of three different Phyllanthus extracts on the serologic status of 123 patients with chronic hepatitis B. Eleven patients received an extract of Phyllanthus amarus (L) provided by S.P. Thyagarajan, Madras, India. Forty-two patients received Phyllanthus niruri (L), gathered from Hainan Province in China, and 35 patients received an extract of Phyllanthus urinaria (L), which had been gathered in Henan Province. Thirty-five control patients received no herbal therapy. The patients receiving Phyllanthus urinaria (L) were both more likely to lose detectable hepatitis B e-antigen from their serum and more likely to seroconvert hepatitis B e-antibody status from negative to positive than were patients given either of the other two preparations. No patient changed status with respect to hepatitis B s-antigen.

Wu Chunrong, et al., 33 patients with hepatitis C treated by TCM syndrome differentiation, Chinese Journal of Integrated Traditional and Western Medicine for Liver Diseases 1994; 4(1): 44–45.

Yao Zhen, Liu Maocai, and Wang Chaolian, A preliminary report on the affect of 911 Granules on chronic viral hepatitis of the B and C types, Journal of Integrated Traditional and Western Medicine 1995/3.

Yamashiki M, et al. Efficacy of a herbal medicine "sho-saiko-to" on the improvement of impaired cytokine production of peripheral blood mononuclear cells in patients with chronic viral hepatitis. J Clin Lab Immunol. 1992; 37(3): 111-121.

Yamashiki M, Nishimura A, Suzuki H, Sakaguchi S, Kosaka Y. Effects of the Japanese herbal medicine "Sho-saiko-to" (TJ-9) on in vitro interleukin-10 production by peripheral blood mononuclear cells of patients with chronic hepatitis C. Hepatology 1997 Jun;25(6):1390-1397.

Abstract: "Sho-saiko-to" (TJ-9) consists of 7 herbal components. In Japan, it is widely prescribed to patients with chronic viral liver disease. TJ-9 is known to suppress liver cancer development and possess macrobiotic effects, but its mode of action is not fully understood. This study investigated the following: 1) cytokine production levels, mainly interleukin (IL)-10, in peripheral blood mononuclear cells of chronic active hepatitis B and C patients, and healthy volunteers; 2) effects of TJ-9 on these productions; and 3) effects of each of its herb components on cytokine production in cell fractions. Results showed that without stimulants, IL-10 production in mononuclear cells of hepatitis B and C patients was significantly lower than that of healthy subjects (P < .01). IL-10 production induced by either phytohemagglutinin (PHA) or pokeweed mitogen (PWM) in mononuclear cells of hepatitis C patients

were significantly lower than in patients with hepatitis B (P < .01) and healthy subjects (P < .05). IL-10 production induced by anti-CD3 or lipopolysaccharide (LPS) was significantly lower than in healthy subjects (P < .05). The addition of TJ-9 to the cultures strongly induced IL-10, and this induction was mainly attributable to the effects of 2 components (scutellaria root and glycyrrhiza root) on the monocyte/macrophage fraction. The production of IL-4 and IL-5 in cultures with concanavalin A (conA) was significantly higher in patients with hepatitis C than in the healthy subjects (P < .01; P <.05), but the addition of TJ-9 suppressed these increases by 25% to 33% (P < .01). Therefore, TJ-9 could adjust the decreased IL-10 production and the increased IL-4 and IL-5 production of mononuclear cells from patients with hepatitis C. Moderate regulation of the cytokine production system in patients with hepatitis C by using TJ-9 may be useful in the prevention of disease progression.

You Songxin, et al., Clinical research on hepatitis-C treating oral liquid, Journal of Traditional Chinese Medicine 1996; 37(11): 673–675.

Zheng MS, Zhang YZ. [Anti-HBsAg herbs employing ELISA technique]. Chung Hsi Chieh Ho Tsa Chih 1990 Sep;10(9):560-2, 518. [Article in Chinese]

Abstract: With the aid of the ELISA system this schema represented a laboratory approach to the recognition of anti-HBsAg capability of herbs by using 300 herbal extracts. Altogether 10 herbs (3.0%) were identified as effective. When forming a multiplex plan by employing 10 average P/N ratios as exemplified by 5 varying doses of herb (0.3, 0.6, 1.2, 2.5, 5.0 mg/100 microliters), 2 varying concentrations of HBsAg (10.92, 14.26 P/N ratio), and 3 varying contact time periods (immediate, 1h, 2h) for the comprehensive appraisal of herb efficacy index, these 10 effective herbs were listed in the following order: Prunella vulgaris (1.00), Litchi chinensis (1.26), Gossypium herbaceum (1.45), Cudrania cochinochinensis (1.56), Caesalpinia sappan (1.73), Oldenlandia tenelliflora (1.77), Cautis parthenocissus (1.99), Evodia rutaecarpa (2.01), Portulaca grandiflora (2.44), and Anemone hupehensis (2.83).

Zhou Z. [Application and mechanism of radix et rhizoma rhei in treating diseases of the digestive system]. Chung Kuo Chung Yao Tsa Chih 1989 Aug;14(8):501-3, 512. [Article in Chinese]

Abstract: Radix et Rhizoma Rhei is a commonly used Chinese medicinal herb with unique function. The present, study is concerned with the application and mechanism of the herb in the treatment of diseases of digestive system.