The suppressive effects of Platycodi Radix (Changkil: CK), the root of Platycodon grandiflorum A. DC (Campanulaceae), on the progress of acute carbon tetrachloride $(CCl_4)$-induced hepatic fibrosis were investigated in the rat. CK significantly suppressed $(CCl_4)$-induced hep...
The suppressive effects of Platycodi Radix (Changkil: CK), the root of Platycodon grandiflorum A. DC (Campanulaceae), on the progress of acute carbon tetrachloride $(CCl_4)$-induced hepatic fibrosis were investigated in the rat. CK significantly suppressed $(CCl_4)$-induced hepatic necrosis and inflammation, as determined by the serum enzymatic activities of alanine and aspartate aminotransferase and serum tumor necrosis factor-${\alpha}$ levels, in dose-dependent manners. In addition, the increased hepatic fibrosis after acute $(CCl_4)$ treatment was suppressed by the administration of CK. CK also significantly prevented the elevation of hepatic ${\alpha}$ 1(I) procollagen (type I collagen) mRNA and ${\alpha}$ -smooth muscle actin (${\alpha}$ -SMA) expressions in the liver of $(CCl_4)$-intoxicated rats and also suppressed the induction of ${\alpha}$ -SMA and type I collagen in cultured hepatic stellate cells, in dose-dependent manners. These results suggest that the suppressive effects of CK against the progress of acute $(CCl_4)$-induced hepatic fibrosis possibly involve mechanisms related to its ability to block both hepatic inflammation and the activation of hepatic stellate cells.
The suppressive effects of Platycodi Radix (Changkil: CK), the root of Platycodon grandiflorum A. DC (Campanulaceae), on the progress of acute carbon tetrachloride $(CCl_4)$-induced hepatic fibrosis were investigated in the rat. CK significantly suppressed $(CCl_4)$-induced hepatic necrosis and inflammation, as determined by the serum enzymatic activities of alanine and aspartate aminotransferase and serum tumor necrosis factor-${\alpha}$ levels, in dose-dependent manners. In addition, the increased hepatic fibrosis after acute $(CCl_4)$ treatment was suppressed by the administration of CK. CK also significantly prevented the elevation of hepatic ${\alpha}$ 1(I) procollagen (type I collagen) mRNA and ${\alpha}$ -smooth muscle actin (${\alpha}$ -SMA) expressions in the liver of $(CCl_4)$-intoxicated rats and also suppressed the induction of ${\alpha}$ -SMA and type I collagen in cultured hepatic stellate cells, in dose-dependent manners. These results suggest that the suppressive effects of CK against the progress of acute $(CCl_4)$-induced hepatic fibrosis possibly involve mechanisms related to its ability to block both hepatic inflammation and the activation of hepatic stellate cells.
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문제 정의
fibrosis remains. Therefore, the present study was undertaken to evaluate the suppressive effects of CK on the early phase of acute CCI4-induced progress of hepatic fibrosis and elucidate the mechanism(s) underlying these protective effects in the rat and the a-SMA and type I collagen expression of rat cultured HSCs. Our results indicate that CK significantly prevented CCI4-induced progress of hepatic fibrosis.
제안 방법
). Sub-sequently, CK or vehicles alone, as controls, were treated once daily for 3 consecutive days, and liver samples obtained 24 h after the final treatment. The liver sections were stained with Masson's trichrome (200x).
). Sub-sequently, CK or vehicles alone, as controls, were treated once daily for 3 consecutive days, and liver samples obtained 24 h after the final treatment. The liver sections were stained with Masson's trichrome (200x).
The effects of CK on the changes in the inflammatory responses caused by CCI4 were assessed by measuring the serum TNF-α levels. A single dose of CCI4 treatm이V increased the serum TNF-α level at 12 h, as determined by ELISA (Fig.
To investigate the suppressive effect of CK on the progress of acute CCI4-induced hepatic fibrosis, rats were given a single treatment of CCI4. The effects of CK on the extent of early phase hepatic fibrosis were evaluated by histopathological examination of liver sections by H&E staining following 3 days of CCI4 treatment. In contrast to the control group (Fig.
Fixed tissues were routinely processed, and then embedded in paraffin, sectioned, deparaffinized and rehydrated using standard techniques. The extents of CCI4-induced necrosis and fibrosis were evaluated by assessing the morphological changes in liver sections stained with hematoxylin and eosin (H&E) and Masson's trichrome, respectively, using standard techniques. α-SMA for the detection of activated hepatic stellate cells was immunchistochernically assessed by the avidin-biotin-peroxidase complex method, as previously described (Sakaida et al.
This suppression of the a-SMA expression suggests CK may have blocked the synthesis of type 1 collagen, as discussed above, at least partially, by preventing the differentiation of HSCs into myofibroblasts in cultures of HSCs in vitro. To eliminate the possibility that CK might be toxic toward HSCs, the cell viability was assessed using the MTT assay, which showed CK did not alter the cell viability at the concentrations used in the experiment (data not shown).
Groups of control animals were given the respective vehicles. Twelve, 24 and 72 h after the CCI4 treatment, the rats were anesthetized with CO2, blood removed by cardiac puncture, to determine the serum ALT and AST activities and serum TNF-α levels, and the animals decapitated. After bleeding, the livers were weighed and a thin sllce preserved in a buffered formalin solution to obtain histological sections.
대상 데이터
The authors are grateful to Jangsaeng Doraji Co., Ltd., Chinju, South Korea for providing the root of P. grandiflorum.
데이터처리
results reported as means±SD. ANOVA was used to evaluate the difference between multiple groups. If significance was observed between groups, a Dunnets t test was used to compare the means of the two specific groups in question, with P < 0.
성능/효과
In conclusion, CK suppresses the progress of CCI4-induced hepatic fibrosis in vivo, and these effects may be due to its ability to block the activation of Kupffer cells and HSCs. Recently, much attention has focused on the pro-tective biochemical function of naturally occurring antioxidants in biological systems, and on their mechanism of action.
후속연구
, 1991), the saponins derived from CK could prevent HSCs activation and inhibit the progress of CCI4-induced hepatic fibrosis. However, further studies are needed in order to clarify the exact mechanism(s).
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