Ssanghwa-tang (SHT) is a traditional herbal medicine formula that has been used for the development of physical strength, relief of pain, and the reduction of fatigue. In this study, we fermented SHT with
Lactobacillus fermentum
(L. fermentum),
Lactobacillus gasseri
(L.gasseri), or
Lactobacillus casei
(L.casei) to investigate the hepatoprotective effects of SHT and fermented SHT with
Lactobacillus
on carbon tetrachloride (CCl4)-induced liver injury in rats. Rats were given CCl4 (1 ml/kg, 50% CCl4 in olive oil) intraperitoneally and either SHT or fermented SHTs (15 ml/kg) was administered 30 min before CCl4. At 24 hr after CCl4 injection, the levels of transaminases in the serum were markedly increased. These increases were significantly attenuated by either SHT +
L. fermentum or SHT+
L.gasseri. However, SHT and SHT +
L.casei showed slight suppression of the increase of transaminases. The liver histological changes were diminished by treatment with SHT +
L. fermentum. Additionally, the potential hepatoprotective effect of fermented-SHTs correlated with the amount of unknown metabolite which is produced during fermentation process with
L. fermentum, L.gasseri, or
L.casei. Therefore, these results suggest that the hepatoprotective effect of SHT may be improved by fermentation with
L. fermentum and the intestinal bacterial enzyme activities may likely play an important role in the pharmacological action of herbal medicines.