Myeong-Jong Lee

In vitro and in vivo protective effects of fermented preparations of dietary herbs against lipopolysaccharide insult

Lipopolysaccharide (LPS) is known to produce endotoxic shock by triggering systemic inflammatory responses. Here, we evaluated the protective effects of three fermented/re-fermented herbs, Rhizoma Atractylodis Macrocephalae, Massa Medicata Fermentata, and Dolichoris Semen, in an LPS-mediated inflammatory insult, either individually in vitro using RAW264.7 cells or in combination in in vivo using rats. In general, each of the fermented herbs showed appreciable in vitro anti-inflammatory activity, although the degree of this activity varied with the herb used. Moreover, a mixture of fermented herbal extracts in combination with probiotics significantly attenuated the blood endotoxin and CRP levels, as well as the gut permeability, and significantly augmented the intestinal Lactobacillus spp. colonisation in LPS-treated rats. However, these effects were not observed following the administration of the corresponding mixture of unfermented herbal extracts. Thus, our results highlight the beneficial impacts of the use of fermented herb products with probiotics to combat LPS-mediated inflammatory insults.

Genotoxicity study of bojungchisup-tang, an oriental herbal decoction-in vitro chromosome aberration assay in Chinese hamster lung cells andin vivo supravital-staining micronucleus assay with mouse peripheral reticulocytes

The toxicity evaluation of oriental herbal drugs is of great concern at present. Bojungchisuptang (BCST, in Korean), a decocted medicine of oriental herbal mixture, is now well used in clinic at oriental hospitals for the treatment of edema of several diseases in practice. However, the toxicity of the oriental herbal decocted medicines such as genetic toxicity is not well defined until now. In this respect, to clarify the genetic toxicity of BCST,in vitro chromosome aberration assay with Chinese hamster lung (CHL) fibroblasts andin vivo supravital micronucleus assay with mouse peripheral reticulocytes were performed in this study. In the chromosome aberration assay, we used 5,000 μg/ml BCST as maximum concentration because no remarkable cytotoxicity in CHL cells was observed both in the presence and absence of S-9 metabolic activation system. No statistical significant differences of chromosome aberrations were observed in CHL cells treated with 5,000, 2,500 and 1,250 μg/ml BCST for 6 hour both in the presence and absence of S-9 metabolic activation. However, very weak positive result (6.5∼8.0% aberration) of BCST was obtained in the absence of S-9 metabolic activation system at 5,000 μg/ml BCST when treated for 24 hour, i.e. 1.5 normal cell cycle time. And also,in vivo clastogenicity of BCST was studied by acridine orange-supravital staining micronucleus assay using mouse peripheral reticulocytes. We used 2,000 mg/kg as the highest oral dose in this micronucleus assay because no acute oral toxicity of BCST was observed in mice. The optimum induction time of micronucleated reticulocytes (MNRETs) was determined as 36 hours after oral administration of 2,000 mg/kg BCST. No significant differences of MNRETs between control and BCST treatment groups were observedin vivo micronucleus assay. From these results, BCST revealed very weak positive result in chromosome aberration assayin vitro with CHL cells and no clastogenicity in micronucleus assayin vivo.

Intestinal Protective Effects of Herbal-Based Formulations in Rats against Neomycin Insult.

Disturbance in the gut microbial niche by antibiotics like neomycin produces gastrointestinal (GI) disorders. Here, we evaluated the impact of a mixture of extracts of three herbs (Atractylodis Rhizoma Macrocephalae, Massa Medicata Fermentata, and Dolichoris Semen) with known GI protective activities, either laboratory unfermented (herbal formulation-1 (HF-1)) or fermented/re-fermented (herbal formulation-2 (HF-2)) on neomycin-treated rats using a commercial Lactobacillus probiotic as a reference. Treatment with neomycin augmented stool water content, decreased fecal population of Lactobacillus spp., changed the histology of intestine without inducing inflammation, reduced the colonic expression of zonula occludens-1 (ZO-1) and claudin-1, and elevated the serum C-reactive protein (CRP) and interferon-gamma (IFN-γ) levels. Coadministration of either HF-2 or probiotic, but not HF-1, restored the fecal content of Lactobacillus spp., normalized the serum CRP level, and significantly increased the colonic expression of ZO-1 and claudin-1 in neomycin-treated rats. The combined treatment with any of the above agents ameliorated the histological changes of cecum and colon in neomycin-treated rats, and the magnitude of this effect was probiotic > HF-2 > HF-1. Our study revealed the intestinal protective effect of a mixture of three herbs against neomycin insult, which is mediated through multiple mechanisms and is potentiated upon prior fermentation/refermentation of the herbs.