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Table of Contents
REVIEW ARTICLE
Year : 2017  |  Volume : 3  |  Issue : 3  |  Page : 46-50

Xiao chai hu tang for liver diseases: A literature review


1 Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
2 Clinical Research Institute of Integrated Traditional Chinese and Western Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China

Date of Submission01-Sep-2016
Date of Acceptance03-May-2017
Date of Web Publication24-Oct-2017

Correspondence Address:
Sheng-Liang Zhu
Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/wjtcm.wjtcm_4_17

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  Abstract 

The objective of this study is to summarize the pharmacological effects and the mechanisms of action of Xiao Chai Hu Tang (XCHT, Minor Bupleurum Decoction) on liver diseases, so as to give relevant researchers a valuable insight and benefit patients with hepatopathy. PubMed was used to search for and collect scientific publications related to XCHT and liver diseases from 1986 to 2016. The available scientific results or evidence were read, classified, and analyzed. XCHT showed clinical efficacy in patients with hepatic diseases including hepatitis, hepatic fibrosis, and hepatoma. The mechanisms involved the production of cytokines, the regulation of immune function, the suppression of lipid peroxidation, etc., XCHT might work on the metabolism of some medications such as tolbutamide by the regulation of gastric emptying and intragastric pH. XCHT exhibited a very low toxicity profile, such as interstitial pneumonia due to duration of medication, patients' age, and drug combination. XCHT has been a eutherapeutic supplemental remedy for liver diseases. However, many mechanisms of action and effects of XCHT on new types of liver diseases still remain unclear, so more and more animal experiments and human clinical trials are needed to obtain enough proofs for the clinical use of XCHT in new types of hepatosis such as nonalcoholic fatty liver disease and autoimmune liver disease.

Keywords: Hepatic fibrosis, hepatitis, hepatoma, interstitial pneumonia, tolbutamide, Xiao Chai Hu Tang (minor bupleurum decoction)


How to cite this article:
Wang Y, Li L, Cheng YM, Zhu SL. Xiao chai hu tang for liver diseases: A literature review. World J Tradit Chin Med 2017;3:46-50

How to cite this URL:
Wang Y, Li L, Cheng YM, Zhu SL. Xiao chai hu tang for liver diseases: A literature review. World J Tradit Chin Med [serial online] 2017 [cited 2019 May 23];3:46-50. Available from: http://www.wjtcm.net/text.asp?2017/3/3/46/217099


  Introduction Top


Xiao Chai Hu Tang (XCHT, Minor Bupleurum Decoction), also known as Sho-saiko-to in Japan, is a popular Chinese herbal formula applied in Asia, containing seven medicinal plants: bupleurum root, pinellia ternata, scutellaria root, jujubae fructus, panax ginseng, licorice, and ginger. [Table 1] lists the principal constituents of each herb component. This formula is derived from the book Treatise on Cold Damage Diseases, written by Zhang Zhongjing (a famous physician of the late Eastern Han Dynasty, about 200 A.D.), and now, many experimental and clinical researches including prospective, randomized, and placebo-controlled trials have involved the clinic efficacy of XCHT. Although it has been widely used by patients with different kinds of hepatic diseases, such as hepatitis and liver fibrosis, its benefits claimed need an accurate assessment. This review sums up the available scientific findings about XCHT and hepatic diseases, pointing out the direction for further studies.
Table 1: Components and constituents of Xiao Chai Hu Tang

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  Mechanisms of Action Top


Hepatoprotective effects

XCHT helps to maintain the balance among the immunological cytokines, which may have immunological benefits to chronic viral hepatitis.[1] For example, scutellaria root and licorice in XCHT could induce the production of cytokines such as interleukin (IL)-1 β, tumor necrosis factor (TNF)-α, and granulocyte-colony stimulating factor (G-CSF) from monocytes/macrophages.[2] Kakumu et al.[3] found XCHT increased interferon-γ (IFN-γ) and antibody against HBV, strengthening cellular and humoral immune responses. To patients with chronic hepatitis C, Yamashiki et al.[4] pointed out that XCHT could mediate the levels of IL-4, IL-5, and IL-10 to prevent the disease progression. In imprinting control region (ICR) mice with liver injury induced by D-galactosamine, oral administration of XCHT for 14 days resulted in a significant decrease of IL-6 and TNF-α levels in the serum, a similar reduction of Fas mRNA, FasL mRNA, and Bax protein expression, but an increase of the Bcl-2 mRNA expression in the liver tissues, and finally, XCHT relieved this kind of liver injury through the mechanism above.[5]

How XCHT and its components work on the count and proliferation of T-cell subsets in splenic cells and hepatocytes in vitro has also been examined. The data indicated that XCHT selectively inhibited the proliferation of CD8+ T-cell to regulate the CD4/CD8 ratio due to the constituent wogonin-7-O-glucuronide and its metabolin, which might take an essential role in the treatment of chronic hepatitis.[6] In other words, the therapeutic effect of XCHT might be improving body resistance, removing evil pathogen, and strengthening or regulating immune function.[7] The potent synergistic effect of XCHT on opsonic intracavitary of HBV carrier has also been confirmed in a mouse model, which inspires a widespread use of XCHT in immune therapies.[8]

Chang et al.[9] tested the anti-HBV activity of XCHT in HepG(2) 2.2.15 cell model and found XCHT could be supplementary to nucleotide analogs to minimize the recurrence of viremia after its discontinuation; however, this effect might not be mediated by saikosaponin A.

Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of excessive fat in the liver of a patient who has no history of alcohol abuse. Db/db mice fed on a methionine- and choline-deficient diet, as animal models of nonalcoholic steatohepatitis (NASH), and were treated with XCHT for 4 weeks. After biochemical, pathological, and molecular analyses, it was revealed that the value of serum alanine aminotransferase (ALT) and the degree of liver necroinflammation and fibrosis, were dramatically improved by XCHT and meanwhile malondialdehyde levels in liver tissues were lower after treatment. All these suggested XCHT might inhibit hepatic necroinflammation and fibrosis in patients with NASH.[10] Studies of Nammi's laboratory reported the underlying mechanisms of ginger as one component of XCHT formula in regulating hepatic cholesterol and lipid metabolism of high-fat diet (HFD)-fed rats,[11],[12] whose hypercholesterolemia were mainly regulated by increased hepatic low-density lipoprotein receptor and reduced 3-hydroxy-3-methyl-glutaryl-CoA reductase. HFD-induced hepatic inflammation was proved to attenuate because of ginger extract through inhibition of nuclear factor-kB (NF-kB).[13] Gao et al. verified that ethanolic extract of ginger (50 mg/kg) significantly reduced dyslipidemia and hepatic lipid accumulation in fructose-induced NASH by modulation of the hepatic carbohydrate response element-binding protein-mediated pathway.[14]

Antifibrogenic effects

In rats whose bile ducts were ligated, XCHT was found to reduce cholestasis significantly, cut down the collagen content by 50%, and exert antifibrogenic effect by down-regulating hepatic mRNA expression of procollagen alpha-1 type I, type III, and tissue inhibitors of metalloproteinase (TIMP)-1.[15] The balance of matrix metalloproteinases (MMPs) and TIMPs was the further breakthrough point of research on XCHT. MMP had degradative activity against collagen, whereas TIMP controlled the active forms of MMP by blocking the active site of it. Sakaida et al.[16] claimed XCHT raised MMP-2, 13 activities and inhibited TIMP-1, 2 activities of hepatic stellate cells (HSCs) probably by P38 pathway. In an in vitro study,[17] XCHT significantly accumulated the stellate cells, transforming morphologically to myofibroblast-like cells in the G0/G1 phase, and decreased cell number subsequently in G2/M phase. From further insight into XCHT, baicalin and baicalein belonging to flavonoids had the ability to inhibit the activation of HSCs against fibrosis.[18],[19]

XCHT also suppressed fibrogenesis by reduction of lipid peroxides, and this preventive effect was shown in inhibiting both lipid peroxidation in cultured rat hepatic cells which were in the state of oxidative stress, and generation of alpha-smooth muscle actin, type I collagen expression, cell multiplication, and oxidative burst in cultured rat HSCs considered as the main collagen-producing cells.[19],[20] In addition, XCHT showed its dose-dependent suppression to Fe2+/adenosine 5'-diphosphate-induced lipid peroxidation in rat hepatic mitochondria and its ability of free radical elimination.[19]

Ono et al.[21] holded that administration of XCHT brought about an increase in retinoid level and a decrease in hydroxyproline level of liver, inhibiting activation of Ito cells, and then, causing inhibition of collagen production and prevention of liver fibrosis. However, when active constituents of XCHT were taken alone, liver retinoid levels remained low, implying that it was interaction among active constituents of XCHT that suppressed activation of Ito cell.[22]

Antihepatoma effects

XCHT-induced TNF-α and G-CSF in vitro in peripheral blood mononuclear cells of patients with hepatocellular carcinoma (HCC), which might be the source of benefits for patients taking administration of XCHT to deal with hepatoma.[23]

A subsequent study suggested that XCHT prevented hepatocarcinogenesis with inhibition of 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation, which played an important role in oxidative stress.[24] Meanwhile, the vicious circle between the oxidative stress and the alkaline phosphatase inactivation through lipopolysaccharides (LPS)-catecholamines interactions in the gut, liver, and brain could be attenuated by XCHT during CCI4+ ethanol-induced mouse HCC.[25]

Besides, XCHT was proved to suppress the proliferation of the carcinoma cell lines in morphological, DNA, and cell cycle analyses, inducing apoptosis in the early period of exposure and arrest at the G0/G1 phase in the late period of exposure. The suppressive effect of XCHT was stronger than each of its major ingredients, and almost no inhibition was observed in normal human peripheral blood lymphocytes or normal rat hepatic cells.[26] Other researches demonstrated that baicalein, baicalin, and saikosaponin A suppressed cultured human hepatoma cell proliferation in a dose-dependent manner but irrelevant to the cell cycle. Furthermore, it was reported that saikosaponin A possessed strong cell-killing ability, but saikosaponin C, ginsenoside Rb1, and ginsenoside Rg1 did not work on cell proliferation.[27]

Afterward, XCHT was shown to improve the immune function of tumor-bearing mice to inhibit the growth of solid liver cancer.[28]

However, Watanabe et al.[29] found the number of Glutathione S-transferase placental form positive areas within the HCC lesions was smaller in both the control and the lycopene group than that in the XCHT group (P = 0.024 and P = 0.012, respectively), which meant long-term administration of XCHT did not reduce the risk of hepatocarcinogenesis in Long–Evans cinnamon rats.


  Human Clinical Trials Top


Hepatitis

In an in vivo study,[30] XCHT seemed to help eliminate HBeAg in children. Among the 24 chronic hepatitis C patients who were not candidates for IFN-based therapy and received XCHT at the dose of 2.5 g three times daily for 12 months, aspartate aminotransferase of 67% of participants, ALT of 75% of participants, viral load response of 29% of participants and histology activity index scores of 38% of participants were improved according to the assay. The data supported the notion that XCHT could improve liver pathology in selected hepatitis C patients who were not candidates for IFN-based treatment.[31] Another trial, in which 26 healthy participants received XCHT at the dose of 2.5 g twice daily for 5 days and underwent the caffeine test on day 1 and day 5,[32] showed that the mean activity of cytochrome P450 enzymes 1A2 (CYP1A2) reduced by 16% on both 1st day and 5th day compared with the baseline; the mean activity of xanthine oxidase (XO) also dramatically reduced by 25% on 1st day and 20% on 5th day compared with the baseline; the activity of cytochrome P450 enzymes 3A tended to be lower on 5th day than the baseline. In brief, XCHT reduced CYP1A2 and XO activity in human.

Hepatic fibrosis

The herbal medicine XCHT has been administered to a huge number of patients with chronic liver diseases. In patients with HCV-positive liver cirrhosis, the life-extending effect of XCHT was attributed to two of its seven herb components, that was, scutellaria root and licorice. The mechanism might include the promotion of IL-12 production.[33]

Hepatoma

XCHT is known to dramatically inhibit development of hepatoma and plays a role in life prolongation. Oka et al.[34] performed a prospective, randomized, nonblind controlled study that revealed XCHT could help to prevent the progression of HCC in patients with cirrhosis, especially in patients without HBs antigen.


  Potential Drug Interaction Top


Because of current popularity of XCHT in hepatic disease, cancer, and other diseases, it is essential to determine whether it has an effect on cytochrome P450, the hepatic enzyme system in charge of metabolism of many medications.

Nishimura et al.[35] took the attitude that XCHT cut down the bioavailability of tolbutamide (a sulfonylurea hypoglycemic agent) in rats after oral administration, but it made no effect on the intravenous administration of tolbutamide. That was to say, the above change was not related to hepatic metabolism.

Simultaneously, they claimed that XCHT had an inhibition on the gastric emptying and an increase on the intragastric pH, leading to the lower plasma concentration of tolbutamide after oral administration, but it affected neither the intragastric dissolution nor the gastric absorption of tolbutamide. This view contradicts the previous conclusion that XCHT slightly hastened the gastrointestinal absorption of tolbutamide, which might enhance the hypoglycemic effect of the sulfonylurea in the early period after oral administration.[36],[37]


  Side Effects Top


Some case reports have shown the side effects of XCHT, most of which are interstitial pneumonia and acute respiratory failure in Japan.[38] Patients often manifested with coughing, dyspnea, and acute episodes of fever. Chest radiographs revealed diffuse frosted glass shadows and infiltration. There were significant increases above normal in both serum C-reactive protein and lactate dehydrogenase level. Hypoxia was common. Analysis of bronchoalveolar lavage fluid showed abnormally high proportions of lymphocytes and neutrophils and a low CD4/CD8 ratio.[39] As report went, the youngest suffering from interstitial pneumonia attributed to XCHT in Japan was a 7-year-old boy with acute lymphoblastic leukemia complicated by type C hepatitis.[40] At the same time, drug-induced pneumonia due to XCHT occurred in a 71-year-old woman with autoimmune hepatitis.[41] In another autopsy case,[42] it was inferred that the development of interstitial pneumonia was caused by HCV in combination with XCHT-induced lung injury. There was also someone getting hepatic injury and pneumonitis simultaneously after intake of XCHT.[43]

As these case reports show, the morbidity and risk of XCHT-induced interstitial pneumonia are increased by coadministration of IFN,[44],[45] duration of medication, and high in an elderly population.[38] Murakami et al.[46] made it clear that interstitial pneumonia was a side effect of treatment with IFN, and XCHT might potentiate this side effect. A possible mechanism was that XCHT could overstimulate the neutrophils which was caused by IFN to accumulate in the lung. Activated neutrophils released granulocytes elastase and oxygen radicals that might damage lung tissue. When the fibroblasts repaired the damaged tissue, pulmonary fibrosis might occur. Therefore, it is safer for XCHT to be used in patients with hepatic disease who contraindicate IFN. According to Sato,[39] the mean treatment course of XCHT before the occurrence of pneumonitis was 50.2 ± 42.1 days and the mean age was 63.7-year-old.

Nevertheless, Ohtake et al.[47] argued that glycyrrhizin, a metabolite of licorice as one of the primary components in XCHT, raised in vitro IL-6 in anti-CD3 monoclonal antibody (anti-CD3 mAb)-stimulated lung mononuclear cells in a cell-type specific and dose-dependent manner, so XCHT alleviated LPS-induced lung injury at the later phase when lung leak was obvious, but was ineffective on early neutrophil sequestration to the lung in BALB/c mice.


  Conclusions and Other Potential Uses Top


XCHT, a traditional commonly applied Chinese herbal medicine formula, has long been used to patients with hepatic diseases in Asia.[48] In fact, XCHT still has many other effects that have not been exerted. In liver diseases, more and more human clinical trials are needed to obtain enough proofs for the clinical use of XCHT in more aspects, such as NAFLD and autoimmune liver disease. XCHT exhibits a very low toxicity profile and appears to be safe for clinical use and consumption.

Acknowledgment

We would like to thank all those who have contributed their time and knowledge to this manuscript. We also wish to thank two anonymous referees and the academic editors of WJTCM for their very constructive feedback.

Financial support and sponsorship

This work was supported by grants from the Science and Technology Commission Foundation of Shanghai Municipality; China (grants 13401902801).

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Yamashiki M, Kosaka Y, Nishimura A, Takase K, Ichida F. 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;37:111-21.  Back to cited text no. 1
    
2.
Yamashiki M, Nishimura A, Sakaguchi S, Suzuki H, Kosaka Y. Effects of the Japanese herbal medicine 'Sho-saiko-to' as a cytokine inducer. Environ Toxicol Pharmacol 1996;2:301-6.  Back to cited text no. 2
    
3.
Kakumu S, Yoshioka K, Wakita T, Ishikawa T. 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.  Back to cited text no. 3
    
4.
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;25:1390-7.  Back to cited text no. 4
    
5.
Zhou YX, Qiu YQ, Xu LQ, Guo J, Li LJ. Xiao-Chai-Hu Tang in treating model mice with D-galactosamine-induced liver injury. Afr J Tradit Complement Altern Med 2012;9:405-11.  Back to cited text no. 5
    
6.
Ohtake N, Yamamoto M, Takeda S, Aburada M, Ishige A, Watanabe K, et al. The herbal medicine Sho-saiko-to selectively inhibits CD8+ T-cell proliferation. Eur J Pharmacol 2005;507:301-10.  Back to cited text no. 6
    
7.
Liu Z, Xiong M, Zhang H. Experimental study on inhibitory effect of xiaochaihu decoction on duck hepatitis B virus. Zhongguo Zhong Xi Yi Jie He Za Zhi 2000;20:853-5.  Back to cited text no. 7
    
8.
Akbar SM, Yamamoto K, Abe M, Ninomiya T, Tanimoto K, Masumoto T, et al. Potent synergistic effect of Sho-saiko-to, a herbal medicine, during vaccine therapy in a murine model of hepatitis B virus carrier. Eur J Clin Invest 1999;29:786-92.  Back to cited text no. 8
    
9.
Chang JS, Wang KC, Liu HW, Chen MC, Chiang LC, Lin CC. Sho-saiko-to (Xiao-Chai-Hu-Tang) and crude saikosaponins inhibit hepatitis B virus in a stable HBV-producing cell line. Am J Chin Med 2007;35:341-51.  Back to cited text no. 9
    
10.
Takahashi Y, Soejima Y, Kumagai A, Watanabe M, Uozaki H, Fukusato T. Inhibitory effects of Japanese herbal medicines Sho-saiko-to and juzen-taiho-to on nonalcoholic steatohepatitis in mice. PLoS One 2014;9:e87279.  Back to cited text no. 10
    
11.
Nammi S, Sreemantula S, Roufogalis BD. Protective effects of ethanolic extract of Zingiber officinale rhizome on the development of metabolic syndrome in high-fat diet-fed rats. Basic Clin Pharmacol Toxicol 2009;104:366-73.  Back to cited text no. 11
    
12.
Nammi S, Kim MS, Gavande NS, Li GQ, Roufogalis BD. Regulation of low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase expression by Zingiber officinale in the liver of high-fat diet-fed rats. Basic Clin Pharmacol Toxicol 2010;106:389-95.  Back to cited text no. 12
    
13.
Li XH, McGrath KC, Nammi S, Heather AK, Roufogalis BD. Attenuation of liver pro-inflammatory responses by Zingiber officinale via inhibition of NF-kappa B activation in high-fat diet-fed rats. Basic Clin Pharmacol Toxicol 2012;110:238-44.  Back to cited text no. 13
    
14.
Gao H, Guan T, Li C, Zuo G, Yamahara J, Wang J, et al. Treatment with ginger ameliorates fructose-induced Fatty liver and hypertriglyceridemia in rats: Modulation of the hepatic carbohydrate response element-binding protein-mediated pathway. Evid Based Complement Alternat Med 2012;2012:570948.  Back to cited text no. 14
    
15.
Chen MH, Chen JC, Tsai CC, Wang WC, Chang DC, Lin CC, et al. Sho-saiko-to prevents liver fibrosis induced by bile duct ligation in rats. Am J Chin Med 2004;32:195-207.  Back to cited text no. 15
    
16.
Sakaida I, Hironaka K, Kimura T, Terai S, Yamasaki T, Okita K. Herbal medicine Sho-saiko-to (TJ-9) increases expression matrix metalloproteinases (MMPs) with reduced expression of tissue inhibitor of metalloproteinases (TIMPs) in rat stellate cell. Life Sci 2004;74:2251-63.  Back to cited text no. 16
    
17.
Kayano K, Sakaida I, Uchida K, Okita K. Inhibitory effects of the herbal medicine Sho-saiko-to (TJ-9) on cell proliferation and procollagen gene expressions in cultured rat hepatic stellate cells. J Hepatol 1998;29:642-9.  Back to cited text no. 17
    
18.
Shimizu I. Sho-saiko-to: Japanese herbal medicine for protection against hepatic fibrosis and carcinoma. J Gastroenterol Hepatol 2000;15 Suppl:D84-90.  Back to cited text no. 18
    
19.
Shimizu I, Ma YR, Mizobuchi Y, Liu F, Miura T, Nakai Y, et al. Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats. Hepatology 1999;29:149-60.  Back to cited text no. 19
    
20.
Kitade Y, Watanabe S, Masaki T, Nishioka M, Nishino H. Inhibition of liver fibrosis in LEC rats by a carotenoid, lycopene, or a herbal medicine, Sho-saiko-to. Hepatol Res 2002;22:196-205.  Back to cited text no. 20
    
21.
Ono M, Miyamura M, Kyotani S, Saibara T, Ohnishi S, Nishioka Y. Effects of Sho-saiko-to extract on liver fibrosis in relation to the changes in hydroxyproline and retinoid levels of the liver in rats. J Pharm Pharmacol 1999;51:1079-84.  Back to cited text no. 21
    
22.
Miyamura M, Ono M, Kyotani S, Nishioka Y. Effects of Sho-saiko-to extract on fibrosis and regeneration of the liver in rats. J Pharm Pharmacol 1998;50:97-105.  Back to cited text no. 22
    
23.
Yamashiki M, Nishimura A, Nomoto M, Suzuki H, Kosaka Y. 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.  Back to cited text no. 23
    
24.
Shiota G, Maeta Y, Mukoyama T, Yanagidani A, Udagawa A, Oyama K, et al. Effects of Sho-Saiko-to on hepatocarcinogenesis and 8-hydroxy-2'-deoxyguanosine formation. Hepatology 2002;35:1125-33.  Back to cited text no. 24
    
25.
Liu XQ, Hu XJ, Xu HX, Zeng XY. Xiaochaihu Decoction attenuates the vicious circle between the oxidative stress and the ALP inactivation through LPS-catecholamines interactions in gut, liver and brain during CCI4 ethanol-induced mouse HCC. BMC Complement Altern Med 2013;13:375.  Back to cited text no. 25
    
26.
Yano H, Mizoguchi A, Fukuda K, Haramaki M, Ogasawara S, Momosaki S, 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.  Back to cited text no. 26
    
27.
Okita K, Li Q, Murakamio T, Takahashi M. Anti-growth effects with components of Sho-saiko-to (TJ-9) on cultured human hepatoma cells. Eur J Cancer Prev 1993;2:169-75.  Back to cited text no. 27
    
28.
Li J, Xie M, Gan Y. Effect of Xiaochaihu decoction and different herbal formulation of component on inhibiting H22 liver cancer in mice and enhancing immune function. Zhongguo Zhong Yao Za Zhi 2008;33:1039-44.  Back to cited text no. 28
    
29.
Watanabe S, Kitade Y, Masaki T, Nishioka M, Satoh K, Nishino H. Effects of lycopene and Sho-saiko-to on hepatocarcinogenesis in a rat model of spontaneous liver cancer. Nutr Cancer 2001;39:96-101.  Back to cited text no. 29
    
30.
Tajiri H, Kozaiwa K, Ozaki Y, Miki K, Shimuzu K, Okada S. Effect of sho-saiko-to(xiao-chai-hu-tang) on HBeAg clearance in children with chronic hepatitis B virus infection and with sustained liver disease. Am J Chin Med 1991;19:121-9.  Back to cited text no. 30
    
31.
Deng G, Kurtz RC, Vickers A, Lau N, Yeung KS, Shia J, et al. Asingle 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;136:83-7.  Back to cited text no. 31
    
32.
Saruwatari J, Nakagawa K, Shindo J, Nachi S, Echizen H, Ishizaki T. The in-vivo effects of Sho-saiko-to, a traditional Chinese herbal medicine, on two cytochrome P450 enzymes (1A2 and 3A) and xanthine oxidase in man. J Pharm Pharmacol 2003;55:1553-9.  Back to cited text no. 32
    
33.
Yamashiki M, Nishimura A, Huang XX, Nobori T, Sakaguchi S, Suzuki H. Effects of the Japanese herbal medicine “Sho-saiko-to” (TJ-9) on interleukin-12 production in patients with HCV-positive liver cirrhosis. Dev Immunol 1999;7:17-22.  Back to cited text no. 33
    
34.
Oka H, Yamamoto S, Kuroki T, Harihara S, Marumo T, Kim SR, et al. Prospective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9). Cancer 1995;76:743-9.  Back to cited text no. 34
    
35.
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;27:355-63.  Back to cited text no. 35
    
36.
Nishimura N, Naora K, Hirano H, Iwamoto K. Effects of sho-saiko-to (xiao chai hu tang), a Chinese traditional medicine, on the gastric function and absorption of tolbutamide in rats. Yakugaku Zasshi 2001;121:153-9.  Back to cited text no. 36
    
37.
Nishimura N, Naora K, Hirano H, Iwamoto K. Effects of Sho-saiko-to on the pharmacokinetics and pharmacodynamics of tolbutamide in rats. J Pharm Pharmacol 1998;50:231-6.  Back to cited text no. 37
    
38.
Lee JK, Kim JH, Shin HK. Therapeutic effects of the oriental herbal medicine Sho-saiko-to on liver cirrhosis and carcinoma. Hepatol Res 2011;41:825-37.  Back to cited text no. 38
    
39.
Sato A, Toyoshima M, Kondo A, Ohta K, Sato H, Ohsumi A. Pneumonitis induced by the herbal medicine Sho-saiko-to in Japan. Nihon Kyobu Shikkan Gakkai Zasshi 1997;35:391-5.  Back to cited text no. 39
    
40.
Wada Y, Kubo M. Acute lymphoblastic leukemia complicated by type C hepatitis during treatment and further by acute interstitial pneumonia due to Sho-saiko-to in 7-year-old. Arerugi 1997;46:1148-55.  Back to cited text no. 40
    
41.
Katou K, Mori K. Autoimmune hepatitis with drug-induced pneumonia due to Sho-saiko-to. Nihon Kokyuki Gakkai Zasshi 1999;37:641-6.  Back to cited text no. 41
    
42.
Tomioka H, Hashimoto K, Ohnishi H, Fujiyama R, Sakurai T, Tada K, et al. An autopsy case of interstitial pneumonia probably induced by Sho-saiko-to. Nihon Kokyuki Gakkai Zasshi 1999;37:1013-8.  Back to cited text no. 42
    
43.
Daibo A, Yoshida Y, Kitazawa S, Kosaka Y, Bando T, Sudo M. A case of pneumonitis and hepatic injury caused by a herbal drug (sho-saiko-to). Nihon Kyobu Shikkan Gakkai Zasshi 1992;30:1583-8.  Back to cited text no. 43
    
44.
Tojima H, Yamazaki T, Tokudome T. Two cases of pneumonia caused by Sho-saiko-to. Nihon Kyobu Shikkan Gakkai Zasshi 1996;34:904-10.  Back to cited text no. 44
    
45.
Nakagawa A, Yamaguchi T, Takao T, Amano H. Five cases of drug-induced pneumonitis due to Sho-saiko-to or interferon-alpha or both. Nihon Kyobu Shikkan Gakkai Zasshi 1995;33:1361-6.  Back to cited text no. 45
    
46.
Murakami K, Okajima K, Sakata K, Takatsuki K. A possible mechanism of interstitial pneumonia during interferon therapy with sho-saiko-to. Nihon Kyobu Shikkan Gakkai Zasshi 1995;33:389-94.  Back to cited text no. 46
    
47.
Ohtake N, Suzuki R, Daikuhara H, Nakai Y, Yamamoto M, Amagaya S, et al. Modulation of lung local immune responses by oral administration of a herbal medicine Sho-saiko-to. Int J Immunopharmacol 2000;22:419-30.  Back to cited text no. 47
    
48.
Chen YW, Tsai MY, Pan HB, Tseng HH, Hung YT, Chou CP. Gadoxetic acid-enhanced MRI and sonoelastography: Non-invasive assessments of chemoprevention of liver fibrosis in thioacetamide-induced rats with Sho-Saiko-To. PLoS One 2014;9:e114756.  Back to cited text no. 48
    



 
 
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