Comparative Study of the High Molecular Mass Fraction and Low Molecular Mass Fraction of Sho-saiko-to in a Murine Immunologically Induced Liver Injury Model.

Abstract

Many researchers have reported on the efficacies of Japanese and Chinese herbal remedies, so-called kampo-hozai. Since kampo-hozai are mixtures of plant and animal materials and contain numerous ingredients, most researchers have regarded each kampo-hozai as one drug for the investigation of the pharmacological actions using in vivo and in vitro systems. Alternatively, there have been many reports concerning the isolation and structure elucidation of major ingredients and the pharmacological and biochemical actions of crude drugs composing kampo-hozai. However, few reports described the relationship between the mixture, kampo-hozai, and their active ingredients to clarify how their ingredients worked in kampo-hozai function.Sho-saiko-to has been extensively investigated and found to have diverse pharmacological activities. Sho-saiko-to has been used for the treatment of various infectious diseases such as chronic viral hepatitis, [1][2][3] and it has been shown that Sho-saiko-to has immunomodulating activity, [4][5][6][7][8] antiinflammatory effects, [9][10][11] and antihepatitis activity. [12][13][14] Previously, we demonstrated that the immunomodulating actions of Sho-saiko-to, such as augmentation of macrophage function and mitogenic activity, were mainly due to its polysaccharide fractions in vivo. 15,16) Yamaoka et al. also reported the augmentation of natural killer (NK) cells by Sho-saiko-to was mainly due to its acidic polysaccharide fraction and that the polysaccharide fraction of Zizyphi Fructus was involved in this activity. 17,18) Furthermore, the group of Yamada has done much work in this area and isolated 22 types of immunomodulating polysaccharides, which were classified into pectins, pectic arabinogalactans, and pectic heteroglycans, from Juzen-taiho-to. 19) These results suggest that one of the pharmacological roles of the polysaccharide fraction in kampo-hozai is as an immunomodulator. However, the pharmacological roles of the low molecular mass fraction and the interaction of both high and low molecular mass fractions in specific pharmacological action of Sho-saiko-to are still unclear, even though the pharmacological properties of each ingredient composing Sho-saiko-to, such as glycyrrhizin, baicalin, ginsenosides, and saikosaponins, are well characterized.In the present study, we attempt to compare the pharmacological activities of the high molecular mass fraction and the low molecular mass fraction of Sho-saiko-to using an immunologically induced liver injury model to estimate the role of these fractions in the expression of the pharmacological action of Sho-saiko-to. MATERIALS AND METHODS AnimalsMale ICR mice, 5-6 weeks old, were purchased from Shizuoka Laboratory Animal Center (Hamamatsu, Japan). The animals were housed in standard plastic cages in an air-conditioned room (24°C) and given a commercial diet (CE-2, Clea Co., Tokyo, Japan) and water ad libitum. The animals were kept for at least 7 d after their arrival.Chemicals Lipopolysaccharide (LPS, Escherichia coli 0111:B4) was purchase...

Comparative pharmacokinetics of baicalin and wogonoside by liquid chromatography–mass spectrometry after oral administration of Xiaochaihu Tang and Radix scutellariae extract to rats

“…It is composed of seven herbs including Radix bupleuri, Radix scutellariae, Radix glycyrrhizae, Radix ginseng, Rhizoma pinelliae, Rhizoma zingiberis recens, and Fructus jujubae. Xiaochaihu Tang is widely used to treat chronic hepatitis [1][2][3], it also has cytoprotective effects in experimental liver injuries [4,5], preventive and therapeutic effects in experimental hepatic fibrosis via inhibition of hepatic stellate cells and lipid peroxidation in hepatocytes [6][7][8].…”

Separation and isolation methods for analysis of the active principles of Sho-saiko-to (SST) oriental medicine

“…Many clinical and experimental studies have demonstrated the various pharmacological effects of SST. SST, a hot water extract of the mixture of seven medical herbs, is assumed to contain many LMC and HMC, and both groups of compounds have been demonstrated to have important pharmacological activities [49]. Phytochemical analysis of the LMC in the constituent herbs of SST has been performed by a number of investigators, and many LMC have been isolated, characterized, and proven to have biological activities.…”

“…Several methods have been developed to remove HMC from Kampo medicines [17,49], and the method that is frequently used is as follows. SST is first dissolved in 10-fold weight of water and then ethanol is gradually added to its final concentration of 80% (v/v) aqueous ethanol.…”

“…Based on studies on the chemical characterization of the constituent herbs of SST [17,[49][50][51][52][53], it is assumed that the S-fraction contains various classes of compounds with different polarity and structure (i.e., flavonoids, triterpenes, saccharides, amino acids). Therefore, subsequent fractionations of the S-fraction are performed based on either the polarity or the structural properties of compounds.…”

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

“…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).…”