Current research on Sho-saiko-to (SST) from PubMed

SST Inhibits Hepatitis C

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.

Yamashiki M, Nishimura A, Suzuki H, Sakaguchi S, Kosaka Y.
Department of Laboratory Medicine, Mie University School of Medicine, Japan.

Hepatology. 1997 Jun;25(6):1390-7.

"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.

SST Prevent Liver Cancer - Chemoprevention

Prospective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9).

Oka H, Yamamoto S, Kuroki T, Harihara S, Marumo T, Kim SR, Monna T, Kobayashi K, Tango T.
Third Department of Internal Medicine, Osaka City University Medical School, Japan.

Cancer. 1995 Sep 1;76(5):743-9.

BACKGROUND. Most hepatocellular carcinomas (HCC) arise in patients with cirrhosis, in whom its incidence is high. The prevention of HCC in patients with cirrhosis is important. METHODS. A prospective, randomized, nonblind controlled study was performed to evaluate the preventive effect of Sho-saiko-to (TJ-9) on HCC development. TJ-9 is a Chinese herbal medicine that contains crude extracts of seven herbs; it has antitumor effects in experimental animals. Two hundred sixty patients with cirrhosis were randomly assigned to two groups, matched for age, sex, presence of hepatitis B surface antigen, and the severity of liver damage. The patients in the trial group were given TJ-9 at a daily oral dose of 7.5 g in addition to the conventional drugs given to the control patients. The patients were prospectively monitored for 60 months and the cumulative incidence of HCC and the survival rate in the two groups were calculated. RESULTS. The cumulative incidence curve for 5 years of the trial group was lower than that of the control group (P = 0.071). For the patients without HBs antigen, the difference was significant (P = 0.024). The survival curve for 5 years of the trial group was higher than that of the control group (P = 0.053). For the patients without HBs antigen, the difference was significant (P = 0.043). CONCLUSIONS. TJ-9 helped to prevent the development of HCC in patients with cirrhosis, particularly in patients without HBs antigen.

SST Inhibits Hepatitis B

Sho-saiko-to (Xiao-Chai-Hu-Tang) and crude saikosaponins inhibit hepatitis B virus in a stable HBV-producing cell line.

Chang JS, Wang KC, Liu HW, Chen MC, Chiang LC, Lin CC.

Department of Health Care Administration, Chung Hwa University of Medical Technology, Tainan Hsien, Taiwan, ROC.

To search for an effective antiviral agent, this study tested the hypothesis that sho-saiko-to (Xiao-Chai-Hu-Tang) and crude saikosaponins possess the activity directly against HBV and could affect the expressions of viral antigens, HBeAg and HBsAg, in HepG(2) 2.2.15 cell model. The viral amount and viral antigens in the suspension were estimated by quantitative real time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The results showed that sho-saiko-to could inhibit the production of HBV (p < 0.0001), 20 microg/ml sho-saiko-to was efficacious at day-3 of treatment and 10 microg/ml at day-6. The calculated IC(50) and CC(50) of sho-saiko-to were 55.76 microg/ml and 372 microg/ml, respectively, with a selectivity index of 6.67. Crude saponin of B. chinense could also inhibit the replication of HBV (p < 0.0001). Owing to the anti-neoplastic activity of sho-saiko-to and saikosaponin, their calculated CC(50) and selectivity index might be under-estimated. Sho-saiko-to also decreased the expression of HBeAg with the minimal effective concentration of 20 microg/ml. Sho-saiko-to contained too little saikosaponin. Therefore, the anti-HBV activity of sho-saiko-to might not be mediated by saikosaponin. Sho-saiko-to could be supplementary to nucleotide analogues to minimize the recurrence of viremia after its discontinuation.

SST prevents liver fibrosis

Sho-saiko-to prevents liver fibrosis induced by bile duct ligation in rats.

Chen MH, Chen JC, Tsai CC, Wang WC, Chang DC, Lin CC, Hsieh HY.

Research Institute of Chinese Medicine, a China Medical University, Taichung, Taiwan.

Hepatic fibrosis is an over-accumulation of extracellular matrix (ECM). It is a result of an imbalance between collagen synthesis and degradation. Matrix metalloproteinase (MMP) has degradative activity against collagen, but tissue inhibitors of metalloproteinase (TIMP) control the active forms of MMP by blocking the active site of MMP. In our study, we established the bile duct ligated model (BDL) in rats to evaluate anti-fibrotic potential of Chinese medicine sho-saiko-to (TJ-9). We assessed the drug's potential in inhibiting collagen accumulation, suppressing procollagen alpha1 types (I) and (III), and TIMP-1 mRNA expression. After administration of TJ-9, hyperbilirubinemia reduced approximately four-fold when compared with BDL-untreated group. TJ-9 also significantly reduced the collagen content and fibrogenic score, as well as downregulated elevated procollagen alpha1 types (I) and (III) and TIMP-1 mRNA level. Finally, we concluded that (1) TJ-9 significantly reduced cholestasis in rats with BDL, (2) TJ-9 markedly reduced the collagen content by 50%, and (3) TJ-9 exerted its antifibrogenic effect by downregulation of the mRNA expression of procollagen alpha1 types (I) and (III), and TIMP-1 in liver tissue.

SST suppresses acute hepatic injury by CCl4 (carbon tetrachloride)

Effects of Sho-saiko-to extract and its components, Baicalin, baicalein, glycyrrhizin and glycyrrhetic acid, on pharmacokinetic behavior of salicylamide in carbon tetrachloride intoxicated rats.

Taira Z, Yabe K, Hamaguchi Y, Hirayama K, Kishimoto M, Ishida S, Ueda Y.

Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan. tairaz@ph.bunri-u.ac.jp

To elucidate the effects of Sho-saiko-to extract and its components, baicalin, baicalein, glycyrrhizin and glycyrrhetic acid, against the effects of longer periods of acute hepatic injury induced by CCl4, we measured serum ALT activity in male Wistar rats for five days after ip administration of CCl4 (0.2 ml/kg), and examined the daily changes of the pharmacokinetic behavior of salicylamide (SAM) for five days. Serum ALT activity rose to a maximum level within a day after administration of CCl4 and then decreased to the control level after three. Sho-saiko-to extract and its components could suppress this acute change in serum ALT activity to less than 50% of CCl4 alone. However, the pharmacokinetics of SAM showed that liver function recovers in a biphasic manner, so that plasma clearance (CL) decreased significantly at days 1 and 3 after administration of CCl4 (P<0.05). We concluded that the CL change at day 1 corresponds to the acute action of CCl4 intoxication, and that the change at day 3 is effect of physiologically reduced liver function due to the liver regeneration for tissue repair after the CCl4 hepatic injury. Sho-saiko-to extract and its components were shown to suppress acute hepatic injury induced by CCl4, and to bring about an early recovery in liver function.

SST exhibits interferon activity

Xiao chai hu tang inhibits CVB1 virus infection of CCFS-1 cells through the induction of Type I interferon expression.

Cheng PW, Ng LT, Lin CC.

Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Road, Kaohsiung 807, Taiwan.

Coxsackie B virus type 1 (CVB1) infection is known to cause high morbidity and mortality in children, however, there is no effective drug for treating this disease. The present study aimed to examine the antiviral activity of xiao chai hu tang (XCHT), a popular herbal drug for treating viral and bacterial infections, against CVB1 infection and its mechanisms of action. Our data showed that XCHT neutralized the CVB1-induced cytopathic effect in human neonatal foreskin fibroblast cell line (CCFS-1/KMC), with IC50 (virus-induced cytopathic effect by 50%) and EC50 (concentration of 50% effectiveness) values around 12.39 and 50.93 microg/ml, respectively. Its CC50 (concentration of 50% cellular cytotoxicity) and SI (selective index) values were 945.75 microg/ml and 18.92, respectively. These results suggest that XCHT possessed anti-CVB1 activity, and showed no effect on CCFS-1 cell viability and growth at concentration 250 microg/ml. The time-of-addition studies showed that XCHT (50, 100 and 200 microg/ml) added at various time of preinfection (-1 to -3 h), coinfection (0 h) and postinfection (1 approximately 3 h) could inhibit CVB1 infection. Interestingly, XCHT also showed an inhibition on viral replication through the induction of IFN-alpha/beta expression. In conclusion, XCHT possessed antiviral activity against CVB1 infection. It interfered the early stage of viral replication (prophylactic effect) and viral replication after infection (therapeutic effect) through the induction of Type I interferon expression.

SST reduces cancer through apoptosis

Inhibitory effects of herbal drugs on the growth of human ovarian cancer cell lines through the induction of apoptosis.

Zhu K, Fukasawa I, Furuno M, Inaba F, Yamazaki T, Kamemori T, Kousaka N, Ota Y, Hayashi M, Maehama T, Inaba N.

Department of Obstetrics and Gynecology, Dokkyo University School of Medicine, 880 kita-Kobayashi, Mibu, Shimotsuga, 321-0293 Tochigi, Japan. k-zhu@dokkyomed.ac.jp

OBJECTIVE: In order to develop and search for more effective and safe treatments for early and advanced stages of ovarian cancer, we examined the direct effects of four extracts of Chinese herbal drugs on ovarian cancer cells in vitro. METHODS: The growth inhibition of four herbal drugs on a total of six cell lines of human ovarian cancer cells was determined by a Cell Counting Kit-8 by counting viable cells. Apoptotic cells induced by herbal drugs were detected by using MEBCYTO Apoptosis Kit. All experiments were performed in triplicate. The significance of the difference was analyzed with a two-sided Student's t test. A P value less than 0.05 was accepted as statistically significant. RESULTS: The MN, A2780, and KF cell lines exhibited significant growth inhibition in the presence of Sho-saiko-to concentrations of 150 microg/ml, 300 microg/ml, and 500 microg/ml, respectively, and at the concentration of 1000 microg/ml, Sho-saiko-to demonstrated a significant apoptotic induction effect on all six kinds of ovarian cancer cell lines. This concentration is the same as the blood concentration attained when 7.5 g of Sho-saiko-to per day is orally administered and all absorbed. CONCLUSIONS: Sho-saiko-to exhibited significant growth inhibition of ovarian cancer cell lines, and the mechanisms of the inhibitory effects can be attributed, in part, to apoptosis induced by Sho-saiko-to.

Use of SST leads to preventive effects against endotoxemia

Preventive effects of a traditional Chinese medicine (Sho-saiko-to) on septic shock symptoms; approached from heme metabolic disorders in endotoxemia.

Sakaguchi S, Furusawa S, Iizuka Y.

First Department of Hygienic Chemistry, Tohoku Pharmaceutical University, Sendai, Japan. shuhei@tohoku-pharm.ac.jp

Sho-saiko-to, one of the the most frequently prescribed Kampo medicines, is used to treat chronic hepatitis and has shown confirmed clinical efficacy. The present study was performed with respect to heme metabolism to study the preventive effects of Sho-saiko-to against endotoxemia. Endotoxin was injected intraperitoneally at a dose of 6 mg/kg into Sho-saiko-to (500 mg/kg/d, p.o.)-pretreated rats, and its administration clearly prevented the endotoxin-induced hypoferremia. In rats pretreated with Sho-saiko-to, the activity of hepatic delta-aminolevulinate synthetase and cytochrome P-450 level 18 h after endotoxin injection were significantly increased as compared to rats treated with endotoxin alone. Similarly, Sho-saiko-to significantly depressed the endotoxin-induced increase in heme oxygenase activity in liver microsomes. These findings suggested that the extent of shock syndrome caused by endotoxin may be due, at least in part, to changes in heme metabolic disturbance during endotoxemia. Sho-saiko-to may therefore protect rats against lethality caused by endotoxin through its ability to regulate the heme metabolism in septic shock.

SST has preventative effects against endotoxins

Preventive effects of a traditional Chinese medicine (Sho-saiko-to) on endotoxin-induced cytotoxicity and tumor necrosis factor-alpha production in J774A.1 Cells.

Sakaguchi S, Furusawa S.

First Department of Hygienic Chemistry; Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. shuhei@tohoku-pharm.ac.jp

Sho-saiko-to, one of the most frequently prescribed Kampo medicines, is used clinically to treat chronic hepatitis and has shown confirmed clinical efficacy. The present study investigated whether Sho-saiko-to can suppress cytotoxicity and tumor necrosis factor (TNF)-alpha production in endotoxin-treated J774A.1 cells. Sho-saiko-to (10-20 microg/ml) did not affect the proliferation of J774A.1 cells, while a high concentration (50 microg/ml) of Sho-saiko-to induced a slight reduction in cell viability. Treatment with Sho-saiko-to (10-50 microg/ml) significantly inhibited endotoxin (10 microg/ml)-induced cytotoxicity in J774A.1 cells. In addition, Sho-saiko-to (20 microg/ml) suppressed TNF-alpha production by endotoxin (1 microg/ml)-activated J774A.1 cells. These findings suggest that the Kampo prescription Sho-saiko-to suppresses cytotoxicity or TNF-alpha production in macrophages treated with endotoxin and that it may be useful in improving septic shock symptoms. Sho-saiko-to may therefore protect against some of the various disturbances caused by endotoxins through its ability to inhibit TNF-alpha production in septic shock.

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