Possible Mechanisms
Some studies have demonstrated that Sho-saiko-to (SST) probably acts by suppressing inflammation and fibrosis of the liver (Shimizu et al., 1999; Shimizu, 2001; Kusunose et al., 2002; Stickel et al., 2002). SST contains fifteen major low molecular compounds (i.e. baicalin, wogonin-7-O-glucuronide, liquiritin, their three aglycons, liquiritin apioside, glycyrrhizin, saikosaponin b1, saikosaponin b2, ginsenoside Rg1, ginsenoside Rb1, (6)-gingerol, (6)-shogaol and arginine), as well as high molecular weight polysaccharides (Ohtake et al., 2004). Its active ingredient(s) remain unknown. Its biological effect is likely contributed by multiple constituents. SST inhibits the activation of hepatic stellate cells which produce collagen (Kayano et al., 1998). It reduces oxidative stress in hepatocytes and hepatic stellate cells (Kitade et al., 2002). SST was found to increase matrix metalloproteinases activity with reduced tissue inhibitors of metalloproteinases activities on hepatic stellate cells possibly via P38 pathway (Sakaida et al., 2004).
The active components of Sho-saiko-to, baicalin, baicalein and saikosaponin-a have the ability to inhibit cell proliferation. Baicalin and baicalein are flavonoids with chemical structures very similar to silybinin, which shows anti-fibrogenic activities (Shimizu, 2000). SST has shown immunomodulatory activities (Borchers et al., 2000).
In vitro studies show that SST induces mRNA expression of IFN-gamma, interleukin (IL)-12, IL-1beta, IL-10, tumor necrosis factor (TNF)-alpha and granulocyte colony-simulating factor (G-CSF) in human peripheral lymphocytes (Yamashiki et al., 1999; Huang et al., 2001).
In an animal model of cirrhosis, SST significantly reduced the serum fibrotic marker PIII NP, partly by down-regulating transforming growth factor (TGF)-beta1 and platelet-derived growth factor (PDGF) expression. It also suppressed the increasing tendency of IL-1beta and stimulated the production of TNF-alpha to inhibit Ito cell proliferation and collagen formation (Chen et al., 2005). SST potentiates IFN-gamma, IL-4 responses upon anti-CD3 stimulation (Kang et al., 2009). SST, wogonin-7-O-glucuronoside (a major SST ingredient), and wogonin (an intestinal metabolite of wogonin-7-O-glucuronoside) increased CD4/CD8 ratio via a decrease of CD8+ T-cell counts with no effect on CD4+ T-cell counts (Ohtake et al., 2005).
There is evidence suggesting that the high and low molecular mass fractions of SST act in a different manner, with the high molecular mass fraction suppressing the increase in plasma nitric oxide level in an LPS-induced endotoxin shock mouse model but the low molecular mass fraction lacking such activity (Nose et al., 2002).
In a 2011 FDA-approved clinical trial of 24 chronic hepatitis C patients conducted by New York Sloan-Kettering Cancer Center, improvement of aspartate aminotransferase (AST) was observed in 16 (67%) of study participants. Improvement of alanine aminotransferase (ALT) was seen in 18 (75%) patients. Among the 9 (38%) subjects who showed improvement per Knodell’s histology activity index (HAI) scores in paired comparison of pre- and post-treatment liver biopsy (the primary endpoints of the study), 5 (21%) showed an improvement of 2 points or greater. (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 Jun 14;136(1):83-7.)
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