Soyasaponins

HAYASHI, H., HUANG, P.Y., KIRAKOSYAN, A..INOUE, K., HIRAOKA, N., KESHIRO, Y., KUSHIRO, T., SHIBUYA, M EBIZUKA, Y., Cloning and characterization of a cDNA encoding beta-amyrin synthase involved in glycyrrhizin and soyasaponin biosynthesis in licorice, Biol. Pharm. Bull, 2001, 24,912-916. 

Fig. (1). Effects of Extract of Abri Herba in Mice Treated with CC14 Effects of Soyasaponin I (Soya I), total OG-I (OG-I) and total OG-II (OG-II) on CC14 induced liver injury by oral administration. These doses were each 500mg/kg. Each column represents mean of 10 mice. p<0.05, p<0.01. AST (aspartate aminotransferase), ALT (alanine aminotransferase)...

In order to prove the hypothesis obtained from HPLC profile analysis, antihepatotoxic effects of OGs obtained from Abri Herba were tested [30]. The tested OGs were representative ones, soyasaponin I (soyaspogenol B OG, 1) and kaikasaponin III (sophoradiol OG, 21). The antihepatotoxic activity was studied on liver injury induced by CC14 in primary cultured rat hepatocytes [31], Fig. (5). 

Fig. (5). Effects of Some OGs on Primary Cultured Rat Hepatocytes injured with CC14 Effects of glycyrrhizin (GL, triangles), kaikasaponin III (2 1, Kaika III, circles) and soyasaponin I (1, Soya I, squares) on CCI4 (SmM)-induced cytotoxicity in primary cultured rat hepatocytes. The marker of liver injury is the aspartate aminotransferase (AST), measured in IU (International Units)/ . Data are the mean S.D. for three independent cell preparations.

Soyasaponin I (1) inhibited the elevation of aspartate aminotransferase (AST) activity, which was comparable to that of glycyrrhizin (positive control). On the other hand, Kaikasaponin HI (21) was more effective than 1. Compound 21 showed antihepatotoxic activity at less than 100p.g/ml. Furthermore, the highest activity was observed even at lower doses (50, 100pg/ml). Therefore, sophoradiol OGs were concluded to be the anti-hepatotoxic principle in both crude drugs (Abri Heba and Puerariae Flos). 

Glycine soya is a wild-type relative to the cultivated soybean (Glycine max). We isolated four known OGs, soyasaponins 1(1), II (3), III (6) and IV (8) from the aerial parts of this plant [37]. The results of hepatoprotective actions of these OGs are shown in Fig. (7) [37]. 

Fig. (7). Hepatoprotective Actions of Soyasaponins I - IV toward in vitro Immunological Liver Injury on Primary cultured Rat Hepatocytes Control (Cont.) is the value of hepatocytes which were not administered the antiserum. Reference (Ref.) value were administered the antiserum and not treated with Soyasaponins I (A), II (B), III (C), IV (D). Significantly different from Ref., effective p <0.01.

Table 4. Hepatoprotective and Hepatotoxic Activity of for Hydrolytic Products of Kaikasaponin III and Soyasaponin I...

In the meantime, Shiraki reported that glycyrrhizin inhibited the replication of hepatitis B virus after penetrating through hepatocyte membranes [54]. Since soyasaponins I and II also showed antiviral effects against several viruses [18], OG might show not only protective action on hepatocyte membranes but also antiviral action after penetrating through the membranes. Therefore, we tried to elucidate the antiviral effects of OGs in the next section. 

Table 6. Anti-complementary Activity of Soyasaponin I, Kaikasaponin...

Soyasapogenol B, soyasaponins I and II and wistariasaponins from Wistaria brachybotrys (wistariasaponin C corresponds to astragaloside VIII) decreased (20-30%) the Epstein-Barr Virus (EBV) activation induced by the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate) in Raji cells at a concentration of lxlO2 mol ratio [151]. Soyasaponin I from the same plant exhibited remarkable inhibitory effects on mouse skin tumor promotion on the basis of the two-stage DMBA-TPA carcinogenesis test in vivo. Soyasaponin I reduced the number of papillomas per mouse at about 40% even at 20 weeks [152]. 

The effect of soyasaponins on tumor cells may be mediated by mechanisms other than membrane permeability, because of their weak hemolytic activity. Saponins actively interact with cell membrane components, resulting in changes in intracellular morphology and cell membrane permeability. However, the differences between types of saponins and their effects on cell membrane are evident. 

Soyasaponin I and II were studied in vitro against herpes simplex virus type I (HSV-1). Soyasaponin II was more potent than soyasaponin I in the reduction of HSV-1 production. Soyasaponin II was also found to inhibit the replication of human cytomegalovirus, influenza virus, and human immunodeficiency virus type 1. This activity was not due to the inhibition of virus penetration and protein synthesis, but might involve a virucidal effect. When acyclovir and soyasaponin II were evaluated in combination for anti-HSV-1 activity, additive antiviral effects were observed for this virus [160]. Astragaloside II afforded almost 100% protection of T-lymphocytes in vitro against the cytophatic effects of HIV infection. However, the EC50 of ca. 2.5 x 105 molar was difficult to achieve in vivo [98],... 

Alvarez, J.R. and Torres-Pinedo, R. 1982. Interactions of soybean lectin, soyasaponins, and glycinin with rabbit jejunal mucosa in vitro. Pediatr. Res. 16, 728-731. 

Soyasaponin aa (terpene saponin glycoside DDMP ether)... 

Soyasaponin ag (= Soyasapogenol 3-0-glycoside 22-O-DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one) ether) (terpene saponin glycoside DDMP ether)... 

---