There were no differences in serum HBV DNA level between HBeAg-positive and HBeAg-negative chronic hepatitis B with same liver histological necroinflammation grade but differences among grades 1, 2, 3 and 4 apportioned by the same hepatic parenchyma cell volume.

Hepatitis B virus (HBV) DNA levels and liver histological necroinflammation grades are correlated with the antiviral efficacy. It is necessary to clarify the relationship between HBV replication levels apportioned by the same hepatic parenchyma cell volume and severity of liver histological necroinflammation grades in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B. The serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume were compared between HBeAg-positive and HBeAg-negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4, respectively. There were no differences in the serum HBV DNA levels between HBeAg-positive and HBeAg-negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4. However, there were differences in the serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume among liver histological necroinflammation grades 1, 2, 3 and 4 in both HBeAg-positive and HBeAg-negative chronic hepatitis B, respectively. There were no differences in HBV DNA levels with the same liver histological necroinflammation grade activated by HBV wild-type and variant strains. After the differences in hepatic parenchyma cell volume for HBV replication of the same liver histological necroinflammation grade accompanied by different hepatic fibrosis stages were adjusted, the serum HBV DNA level apportioned by the same hepatic parenchyma cell volume was correlated with the severity of liver histological necroinflammation grade.

Dual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smoke.

Previous studies indicate that the arachidonic acid-metabolizing enzymes COX-2 and 5-LOX are overexpressed during the process of colonic adenoma formation promoted by cigarette smoke. The aims of the present study were to investigate whether there exists a relationship between COX-2 and 5-LOX, and whether dual inhibition of COX-2 and 5-LOX has an anticarcinogenic effect in the colonic tumorigenesis promoted by cigarette smoke. Results showed that pretreating colon cancer cells with cigarette smoke extract (CSE) promoted colon cancer growth in the nude mouse xenograft model. Inhibition of COX-2 or 5-LOX reduced the tumor size. In the group treated with COX-2-inhibitor, the PGE2 level decreased while the LTB4 level increased. In contrast, in the 5-LOX-inhibitor treated group, the LTB4 level was reduced and the PGE2 level was unchanged. However, combined treatment with both COX-2 and 5-LOX inhibitors further inhibited the tumor growth promoted by CSE over treatment with either COX-2-inhibitor or 5-LOX-inhibitor alone. This was accompanied by the downregulation of PGE2 and LTB4. In an in vitro study, we found that the action of CSE on colon cancer cells was mediated by 5-LOX DNA demethylation. In summary, these results indicate that inhibition of COX-2 may lead to a shunt of arachidonic acid metabolism towards the leukotriene pathway during colonic tumorigenesis promoted by CSE. Suppression of 5-LOX did not induce such a shunt and produced a better response. Therefore, 5-LOX inhibitor is more effective than COX-2 inhibitor, and blocker of both COX-2 and 5-LOX may present a superior anticancer profile in cigarette smokers.

Effect of polysaccharides from Angelica sinensis on gastric ulcer healing.

Our previous study showed that a crude extract from Angelica sinensis (ASCE), which mainly consisted of polysaccharides, significantly promoted migration and proliferation of normal gastric epithelial cells. These results strongly suggest that ASCE has a direct wound healing effect on gastric mucosa. However, there is no report concerning the effect of ASCE on gastric ulcer healing in animal models. In this study, we found that ASCE promoted ulcer healing. The area of the ulcer was reduced. This was accompanied with a significant increase in mucus synthesis when compared with the control. Angiogenesis was inhibited by the treatment of ASCE. Cell proliferation, ODC and EGFR protein expression was not affected in this process. Thus, the mechanism of how ASCE accelerates ulcer healing in addition to its effect on mucus synthesis remains to be investigated.

Protective effect of polysaccharides-enriched fraction from Angelica sinensis on hepatic injury.

A polysaccharides-enriched fraction from the root of Angelica sinensis, which is known for its antiulcer action on the gastrointestinal tract, was isolated and studied for its hepato-protective effect in rodents. Intra-gastric administration of Angelica sinensis polysaccharides-enriched fraction (AP) at the doses of 50 or 75 mg/kg dose-dependently prevented liver toxicity induced by acetaminophen in mice but did not affect the serum acetaminophen concentration. It normalized the rises of serum alanine transferase (ALT) and hepatic nitric oxide synthase (NOS) activities and the decrease of glutathione level in the liver. It also reduced the hepatic malondialdehyde (MDA) concentration. The protective effect was less evident in the carbon tetrachloride (CCl4)-treated animals including mice and rats. In the rat the elevated serum ALT level was unaffected though the MDA level was similarly reduced by the higher dose of AP. In these animals, CCl4 increased the hepatic glutathione level instead while the NOS activity remained unchanged. These findings suggest that the pathogenic mechanisms of both acetaminophen and CCl4 are different. AP is more effective in the protection against liver damage induced by acetaminophen, which is associated with the glutathione depletion and nitric oxide synthase activation in the liver.

Protective role of heme oxygenase-1 on trinitrobenzene sulfonic acid-induced colitis in rats.

Preliminary studies showed that the inducible form of heme oxygenase (HO-1) was induced and played a protective role in the process of inflammation. The present study investigated the possible role of HO-1 in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. We measured HO-1 activity in TNBS-induced colitis in rats and analyzed the severity of colitis along with altered HO activity by assessing lesion area and myeloperoxidase activity. HO-1 mRNA and protein expressions were determined at different time points after TNBS induction. Free radical production and inducible nitric oxide synthase (iNOS), which participate in oxidative injury, were also assayed. HO activity and HO-1 gene expression increased markedly after TNBS induction. Administration with tin mesoporphyrin (SnMP), a HO inhibitor, potentiated the colonic damage along with a reduction in HO-1 activity. Furthermore, the reduction of HO-1 expression by SnMP also enhanced reactive oxygen species and iNOS expression, both of which were dramatically increased after the TNBS enema. L-Arginine pretreatment further aggravated the injurious action of SnMP. Our results indicate that HO-1 plays a protective role in the colonic damage induced by the TNBS enema, and the preventive effects probably result from decreased free radical production and inhibition of iNOS expression in colonic tissues.

A mechanistic study of proliferation induced by Angelica sinensis in a normal gastric epithelial cell line.

It has been reported that an extract from Angelica sinensis mainly consisting of polysaccharides (95%) prevented ethanol- or indomethacin-induced gastric mucosal damage (Cho CH et al. Planta Med 2000;66:348-51). However, it is not known whether Angelica sinensis has a direct stimulatory effect on the healing of gastric mucosal lesions. To study the hypothesis that Angelica sinensis has a direct mucosal healing effect in rats and in isolated gastric epithelial cells, we assessed the wound repair in both animals and normal cell culture (RGM-1), as well as [3H]thymidine incorporation, ornithine decarboxylase (ODC) activity, and ODC protein and c-Myc protein expression after different treatments in RGM-1 cells. We found that Angelica sinensis crude extract (ASCE) dose-dependently enhanced gastric ulcer healing in rats and promoted wound repair in RGM-1 cells. It also significantly stimulated [3H]thymidine incorporation and ODC activity in RGM-1 cells in a concentration-dependent manner. ODC and c-Myc protein expression was also increased as a result of this process. DL-alpha-difluoromethyl-ornithine repressed the [3H]thymidine incorporation and ODC activity induced by ASCE. Pretreatment with c-Myc antisense oligodeoxynucleotides blocked the stimulatory action of ASCE on [3H]thymidine incorporation and ODC protein expression. These data suggest that ASCE has a direct mucosal healing effect on gastric epithelial cells, while ODC and c-Myc are closely associated with this effect.

Angelica sinensis modulates migration and proliferation of gastric epithelial cells.

A crude extract from Angelica sinensis (ASCE), which mainly consists of polysaccharides, prevents ethanol- or indomethacin-induced gastric mucosal damage and promotes ulcer healing. The aim of this study was to test the hypothesis that ASCE has a direct stimulating effect on gastric epithelial cells for wound healing. We found that ASCE significantly promoted the migration of epithelial cells over an artificial wound on the surface of an RGM-1 monolayer. The extract also stimulated DNA synthesis in a dose-dependent manner and concomitantly increased EGF mRNA expression. Co-incubation of ASCE with anti-EGF antibody reduced the speed of migration and the DNA synthesis, which however were still higher than the control without ASCE. These results strongly suggest that ASCE has a direct wound healing effect on gastric mucosa, and this is acting partially through an EGF-mediated pathway.