About Herbs, Botanicals & Other Products

Sho-saiko-to

Common Name

Xiao-chai-hu-tang, minor bupleurum decoction

Clinical Summary

Sho-saiko-to or “Xiao Chai Hu Tang” is a Chinese botanical formulation widely known by its Japanese name. It contains seven herbs and has been used to treat fever, malaria, gastrointestinal disorders and chronic liver diseases. A prescription form has been used extensively in Japan, predominantly for hepatitis ⁽¹⁾. Sho-saiko-to and its isolated chemical components demonstrate marked antiproliferative effects on hepatoma lines and ovarian cancer cell lines ⁽¹⁵⁾. Morphological analysis of cells grown in the presence of Sho-saiko-to show evidence of apoptosis ⁽⁶⁾. Sho-saiko-to has been shown to prevent liver injury and promote liver regeneration in animal models ⁽⁷⁾ and to enhance various aspects of immune function, including effects on killer cells ⁽¹²⁾, interleukins ⁽⁹⁾, interferon ⁽¹⁰⁾ ⁽¹⁸⁾ and macrophages ⁽¹¹⁾ ⁽¹³⁾. Data also indicate that Sho-saiko-to causes enhancement of granulocyte colony-stimulating factor ⁽¹⁴⁾.
A clinical study shows Sho-saiko-to may improve liver pathology in hepatitis C patients who do not respond to interferon based treatment ⁽²²⁾.
Although Sho-saiko-to has a good safety profile, its use has been associated with interstitial pneumonitis ⁽³⁾, liver injuries ⁽¹⁶⁾ hepatitis ⁽¹⁷⁾. It should only be used under the supervision of a qualified practitioner.

Food Sources

Some of the ingredients, such as jujube, ginger and licorice, are commonly found in Asian recipes.

Purported Uses

Cancer prevention
Cancer treatment
Fever
GI disorders
Infections
Liver disease
Malaria

Constituents

Sho-saiko-to is a mixture of seven botanicals:

Bupleurum root (Chai hu)
Pinellia tuber (Ban xia)
Scutellaria root (Huang qin)
Ginseng (Ren shen)
Jujube (da zao)
Licorice (Gan cao)
Ginger (Sheng jiang)

A number of pharmacologically active components have been isolated including:
Baicalin
Baicalein
Glycyrrhizin
Saikosaponins
Ginsenosides
Wogonin
Gingerols
Given the complexity of Sho-saiko-to, it is unlikely that all active components have been identified.
⁽⁴⁾

Mechanism of Action

Sho-saiko-to (SST) appears to have a multi-factorial activity, inhibiting proliferation of hepatocellular carcinoma (HCC) cells, preventing liver injury, promoting liver regeneration and enhancing immune function. Human studies show reduced incidence of HCC in users of ginseng, one of the botanicals in this formula ⁽⁵⁾. SST and its isolated chemical components demonstrate marked antiproliferative effects on hepatoma lines in vitro. Of particular interest is that SST shows only minimal inhibitory effects on normal human peripheral lymphocytes, even at high concentrations. Morphological analysis of cells grown in the presence of SST shows evidence of apoptosis ⁽⁶⁾. SST prevents liver injury and promotes liver regeneration in animal models: rats treated with SST show less fibrosis as indicated by reduced liver hydroxyproline and a smaller increase in serum hyaluronic acid. Moreover, these rats develop fewer preneoplastic lesions ⁽⁷⁾. SST has also been shown to prevent development or metastasis of carcinomas other than HCC ⁽⁸⁾. SST enhances various aspects of immune function including effects on interleukins ⁽⁹⁾, interferon ⁽¹⁰⁾, macrophages ⁽¹¹⁾ ⁽¹³⁾ and killer cells ⁽¹²⁾. Data also indicate that SST causes enhancement of granulocyte colony-stimulating factor ⁽¹⁴⁾.

Pharmacokinetics

Due to the complexity of this formula, only limited data is available. One study indicates that the serum concentration of glycyrrhizin after a normal daily dose is 1.2 mcg/ml.
⁽²⁾

Warnings

Sho-saiko-to may cause interstitial pneumonitis, a potentially fatal condition. Concurrent use of interferon may increase this risk.
⁽³⁾

Contraindications

Women who are nursing or pregnant and patients currently undergoing interferon treatment should not take Sho-saiko-to.

Adverse Reactions

Sho-saiko-to related pneumonitis has been reported in 74 patients (approximately 1 in 20,000) ⁽³⁾.
Liver injuries and hepatitis have been associated with the use of Sho-saiko-to ⁽¹⁶⁾ ⁽¹⁷⁾.

Herb-Drug Interactions

Interferon: Concurrent use may increase the risk of interstitial pneumonitis ⁽³⁾.
Cytochrome P450 enzymes:
Sho-saiko-to upregulated expression of CYP2B, CYP3A1 and CYP4A1 and can alter the plasma concentration of drugs that are metabolized by these enzymes ⁽¹⁹⁾.
Sho-saiko-to interacts with drugs metabolized by CYP3A4, CYP2C9 and CYP1A2 enzymes ⁽²⁰⁾.
Tolbutamide: Sho-saiko-to reduces the bioavailability following concurrent oral administration ⁽²¹⁾.

Herb Lab Interactions

May affect AST/ALT.

Literature Summary and Critique

Oka H, et al. Prospective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9). Cancer</> 1995;76:743-9.
Two hundred and sixty patients with cirrhosis were randomized using age, sex, heptitis B antigen status and liver function strata to treatment with Sho-saiko-to or control. Patients were followed for 5 years with bimonthly alpha-fetopretein measurement and quarterly ultrasonography. Hepatocellular carcinoma diagnoses were confirmed by angiography, computed tomography and, where indicated, biopsy. Sho-saiko-to led to a one-third reduction in the incidence of hepatocellular carcinoma (23% vs 34%) and a 40% reduction in death (24% vs 40%). Analysis of this data suggests that Sho-saiko-to has multifactorial action, both reducing the incidence of hepatocellular carcinoma and acting as a hepatoprotective agent.

References

Bensky D, Gamble A. Chinese Herbal Medicine: Materia Medica. Revised Ed. Seattle: Eastland Press; 1993.

Mizoguchi Y, et al. The effects of sho-saiko-to oninterleukin production by hepatic sinusoidal endothelial cells. J Med Pharm Soc 1989;6:172-6.

Sato A, at al. Pneumonitis induced by the herbal medicine sho-saiko-to in Japan. Nihon Kyobu Shikkan Gakkai Zasshi 1997;35:391-5.

Honso Professional Catalog 2002. Honso USA, Inc. Tempe, Arizona.

Oka H, et al. Prospective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9). Cancer 1995;76:743-9.

Yano H, et al. The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase. Cancer Res 1994;54:448-54.

Sakaida I, et al. Herbal medicine Sho-saiko-to (TJ-9) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet. J Hepatol 1998;28:298-306.

Ito H, et al. Effects of a blended Chinese medicine, xiao-chai-hu-tang, on Lewis lung carcinoma growth and inhibition of lung metastasis, with special reference to macrophage activation. Jpn J Pharmacol 1986;41:307-14.

Yamashiki M, et al. 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;25:1390-7.

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;13:141-6.

Fujiwara K, et al. Regulation of hepatic macrophage function by oral administration of xiao-chai-hu-tang (sho-saiko-to, TJ-9) in rats. J Ethnopharmacol 1995;46:107-14.

Kaneko M, et al. Augmentation of NK activity after oral administration of a traditional Chinese medicine, xiao-chai-hu-tang (shosaiko-to). Immunopharmacol Immunotoxicol 1994;16:41-53.

Nagatsu Y, et al. Modification of macrophage functions by Shosaikoto (kampo medicine) leads to enhancement of immune response. Chem Pharm Bull (Tokyo) 1989;37:1540-2.

Yamashiki M, et al. Herbal medicine ‘Sho-saiko-to’ induces tumour necrosis factor-alpha and granulocyte colony-stimulating factor in vitro in peripheral blood mononuclear cells of patients with hepatocellular carcinoma. J Gastroenterol Hepatol 1996;11:137-42.

Zhu K, et al. Inhibitory effects of herbal drugs on the growth of human ovarian cancer cell lines through the induction of apoptosis. Gynecol Oncol 2005;97(2):405-9.

Itoh S, Marutani K, Nishijima T, et al. Liver injuries induced by herbal medicine, syo-saiko-to (xiao-chai-hu-tang). Dig Dis Sci. 1995 Aug;40(8):1845-8.

Hsu LM, Huang YS, Tsay SH, et al. Acute hepatitis induced by Chinese hepatoprotective herb, xiao-chai-hu-tang. J Chin Med Assoc. 2006 Feb;69(2):86-8.

Kang H, Choi TW, Ahn KS, et al. Upregulation of interferon-gamma and interleukin-4, Th cell-derived cytokines by So-Shi-Ho-Tang (Sho-Saiko-To) occurs at the level of antigen presenting cells, but not CD4 T cells. J Ethnopharmacol. 2009 May 4;123(1):6-14.

Nose M, Tamura M, Ryu N, Mizukami H, Ogihara Y. Sho-saiko-to and Saiko-keisi-to, the traditional Chinese and Japanese herbal medicines, altered hepatic drug-metabolizing enzymes in mice and rats when administered orally for a long time. J Pharm Pharmacol. 2003 Oct;55(10):1419-26.

Takahashi K, Uejima E, Morisaki T, et al. In vitro inhibitory effects of Kampo medicines on metabolic reactions catalyzed by human liver microsomes. J Clin Pharm Ther. 2003 Aug;28(4):319-27.

Nishimura N, Naora K, Hirano H, Iwamoto K. A Chinese traditional medicine, sho-saiko-to (xiao-chaihu-tang), reduces the bioavailability of tolbutamide after oral administration in rats. Am J Chin Med. 1999;27(3-4):355-63.

Deng G, Kurtz RC, Vickers A, et al. A single arm phase II study of a Far-Eastern traditional herbal formulation (sho-sai-ko-to or xiao-chai-hu-tang) in chronic hepatitis C patients. J Ethnopharmacol. 2011 Apr 17. [Epub ahead of print]

How It Works

Bottom Line: Because limited research has been performed on sho-saiko-to, it should be used only under the supervision of a doctor. It may have liver-protectant effects. There is no evidence that it can treat or prevent any other type of cancer.

From laboratory and animal studies, sho-saiko-to appears to act in multiple ways to prevent liver injury and enhance immunity. Sho-saiko-to and its isolated chemical components show an ability to reduce or stop the proliferation of liver cancer cell lines in the laboratory, but have little effect on normal human white blood cells (this is an advantage because most chemotherapy drugs kill healthy human blood cells as well as tumor cells). In rats, sho-saiko-to prevents liver injury, promotes liver regeneration, and prevents the development of pre-cancerous growths in the liver. Other cancers have also been shown to be sensitive to sho-saiko-to in laboratory tests. In addition, scientists have shown through laboratory tests that sho-saiko-to may stimulate many aspects of the immune system. It is not known whether these effects occur in the human body, but it has been documented that people who use ginseng, one of the herbs found in sho-saiko-to, have a lower risk of hepatocellular carcinoma (liver cancer).

Purported Uses

To prevent and treat cancer
One clinical trial showed that sho-saiko-to was associated with a decreased risk of developing hepatocellular carcinoma (liver cancer) in patients with cirrhosis of the liver. Clinical trials are now being performed to determine whether sho-saiko-to can increase survival in patients with hepatocellular carcinoma.
To reduce fevers
No scientific evidence supports this use.
To treat gastrointestinal disorders
There are no data to back this claim.
To treat infections
No scientific evidence supports this use.
To treat liver diseases, such as cirrhosis and hepatitis
Laboratory and animal studies suggest that sho-saiko-to has a protective effect on the liver. A clinical study show it may improve liver pathology in hepatitis C patients.
To treat malaria
This use is not backed by research.

Research Evidence

Cirrhosis of the liver:
Patients with cirrhosis of the liver are at a greater risk of developing hepatocellular carcinoma (liver cancer). A clinical trial studied the ability of sho-saiko-to to prevent the development of hepatocellular carcinoma in 260 patients with cirrhosis. Patients were randomly given sho-saiko-to or a placebo pill. After five years of follow-up, fewer patients taking sho-saiko-to had developed hepatocellular carcinoma (23% vs 34% in the placebo group) and fewer had died (24% vs 40% in the placebo group). This suggests that sho-saiko-to may act as a liver-protectant.

Patient Warnings

Sho-saiko-to may cause interstitial pneumonitis, a potentially fatal condition. Use of interferon at the same time may increase this risk.
Because it is not regulated by the FDA, this product may be contaminated with other botanicals and/or the concentration listed on the label may be inaccurate.

Do Not Take If

You are pregnant or nursing
You are currently undergoing interferon treatment (This can increase the risk of interstitial pneumonitis, a potentially fatal condition).
You are taking medications that are metabolized by Cytochrome P450 enzymes (Sho-saiko-to upregulated expression of CYP2B, CYP3A1 and CYP4A1 and can alter the plasma concentration of drugs that are metabolized by these enzymes. Sho-saiko-to also interacts with drugs metabolized by CYP3A4, CYP2C9 and CYP1A2 enzymes).
You are taking Tolbutamide (Sho-saiko-to reduces the bioavailability following concurrent oral administration.)

Side Effects

Sho-saiko-to related pneumonitis has been reported in 74 patients (approximately 1 in 20,000).
Liver injuries and hepatitis have been associated with the use of Sho-saiko-to.

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Last updated: May 19, 2011