| Abstract: | 在中醫學的領域裡，龍葵是一種被廣泛用來治療癌症的中草藥植物，對肝癌具有顯著療效。報導指出，其具有保肝、抗發炎的效果，然而龍葵保肝及抗肝癌之能力、有效活性成分及作用機轉，尚不明確。因此本研究首先以萃取龍葵水萃取物(SNE)及龍葵多酚萃取物(SNPE)處理肝癌細胞，探討其抗肝癌之能力及詳細之分子機轉。結果顯示，SNE與SNPE對肝癌細胞之毒性顯著大於正常肝細胞，高濃度SNE與SNPE處理之下，可活化細胞內p-JNK, p-p38, Bax, cytochrome c,及cleaved-caspase 3等apoptotic protein之表現，使肝癌細胞透過apoptosis機制走向凋亡；低濃度之SNE與SNPE處理處理之下，則可活化細胞內autophagc protein: LC3-I, LC3-II及Beclin 1並抑制autopphagy的down-regulaotr: p-mTOR, p-Akt及Bcl-2，促進肝癌細胞透過autophagy機制死亡。另一方面，動物實驗證實，SNE可藉由活化體內之防禦系統GSH, SOD及GSTs，清除氧自由基、氫氧自由基，達到抗氧化與解毒的作用；同時SNE藉由抑制a-SMA, MMP2及p-IKKα,p-IκBα,NFκB等可促進纖維化的signaling pathway並活化抗纖維化機轉TIMP-2及Ras-Raf-p-MEK1/MEK2-p-ERK1/ERK2 signaling pathway，幫助SD大鼠抵抗CCl4所誘導之肝損傷及肝纖維化。此研究結果證實了龍葵保肝、抗肝癌的能力及分子作用機轉，肝癌與肝纖維化的預防與治療提供了一個新的方向。
Solanum nigrum L. (SN) has been used in traditional folk medicine to treat different cancers. It is also used as a hepatoprotective and anti-inflammatory agent. In this study, we demonstrated that the extract of SN (SNE and SNPE) induced a strong cytotoxic effect toward HepG2 cells but much less to Chang liver and WRL-68 cells. The mechanisms of the cytotoxic effect were concentration-dependent. High doses of SNE or SNPE induced apoptotic cell death in HepG2 cells, as evidenced by increases in the expressions of p-JNK, p-p38, Bax, mitochodrial release of cytochrome c, and caspase activation. On the other hand, cells treated with low concentrations of SNE or SNPE revealed morphological and ultrastructural changes of autophagocytic death under electron microscopic observation. Furthermore, these cells showed increased levels of autophagic vacuoles, autophagic proteins: LC3-I, LC3-II, Beclin 1. The levels of p-mTOR, p-Akt and Bcl-2 that have been implicated in the down-regulation of autophagy were decreased upon SNE and SNPE treatment. Taken together, these findings indicate that SNE and SNPE induced cell death in hepatoma cells via two distinct antineoplastic activities of SNE and SNPE, the ability to induce apoptosis and autophagocytosis, therefore suggesting that it may provide leverage to treat liver cancer. Furthemore, the protective effects of water extract of SN (SNE) against liver damage were evaluated in carbon tetrachloride (CCl4)-induced chronic hepatotoxicity in rats. Sprague Dawley (SD) rats were orally fed with SNE along with administration of CCl4. The results showed that the treatment of SNE significantly lowered the CCl4-inuced superoxide, hydroxyl radical and liver damage. The hepatic content of GSH, and activities and expressions of SOD, GSTs that were reduced by CCl4 were brought back to control levels by the supplement of SNE. On the other hand, SNE inhibited MMP2, p-IKKα,p-IκBα,NFκB signaling pathway (fibrogenesis pathway) and activated TIMP-2 and Ras-Raf-p-MEK1/MEK2-p-ERK1/ERK2 signaling pathway (anti-fiborsis pathway). The results of these studies suggest that SNE could protect liver against the CCl4-induced oxidative damage in rats, and this hepatoprotective effect might be contributed to its modulation on anti-fiborsis signaling pathway, detoxification enzymes, its antioxidant and free radical scavenger effects. |
