Echinacoside Stimulates Cell Proliferation and Prevents Cell Apoptosis in Intestinal Epithelial MODE-K Cells by Up-Regulation of Transforming Growth Factor-β1 Expression

Abstract

Abstract. Cistanche deserticola MA (C. deserticola) has been widely used as a laxative herbal in herbal medicine for the treatment of irritable bowel syndrome or constipation, and echinacoside (ECH) is one of the major bioactive ingredients in this herbal. Our aim was to investigate the effect of ECH on intestinal epithelial cell growth and death. MODE-K, an intestinal epithelial cell line, was used as an in vitro model of the intestine. Cell proliferation was measured by methylthiazol tetrazolium (MTT) assay. Cell apoptosis was determined with Annexin-V staining. Here we showed that in cultured MODE-K cells, ECH significantly stimulated cell proliferation and enhanced cell survival by reducing cell apoptosis in the presence of H 2 O 2 or the mixture of pro-inflammatory cytokines, while transforming growth factor (TGF)-β1 expression was up-regulated in a dose-dependent manner. Knockdown of TGF-β1 expression disrupted both the proliferative and cytoprotective activities of ECH, which was further confirmed by neutralization of TGF-β1 activity using anti-TGF-β1 antibody. These data suggest that ECH as one of bioactive ingredients in herbal C. deserticola and others may improve mucosal tissue repair by stimulating intestinal epithelial cell proliferation and preventing cell death via up-regulation of TGF-β.

A Review of Biologically Active Natural Products from a Desert Plant <i>Cistanche tubulosa</i>

“…Furthermore, a new and a known corresponding sugar ester, kankanose 22) (56) and cistanoside F 89) (57), were also obtained (Chart 3). (69). Among the isolates, D-mannitol (69) gave the most highest isolation yield in our study.…”

“…[59][60][61] Among them, echinacoside 62,63) (28) and acteoside [64][65][66][67] (29, also called verbascoside, kusaginin, and orobanchin) are representatives of the well-studied phenylethanoid glycosides and have been reported to possess a number of important bioactive properties such as antioxidative, neuroprotective, nitric oxide radical scavenging, antihepatotoxic, and antiosteoporotic activities. [2][3][4]6,[59][60][61][68][69][70][71][72][73][74][75][76][77] As phenylethanoid glycoside constituents from the stems of C. tubulosa, we have isolated the above-mentioned echinacoside 78) (28) and acteoside 78) (29) (54), and campneoside II 86,87) (55). Furthermore, a new and a known corresponding sugar ester, kankanose 22) (56) and cistanoside F 89) (57), were also obtained (Chart 3).…”

TRAIL pathway is associated with inhibition of colon cancer by protopanaxadiol

“…After 24 hr, the medium was changed and PPD was added at different concentrations. After treatment for 48 hr, all adherent cells were collected with 0.05% trypsin, including the floating cells in the medium, and centrifuged for 5 min at 600 g. Then, the cells were double stained with Annexin-V-(FITC) and propidium iodide (PI) (Becton Dickinson, San Diego, CA) according to the manufacturer's instructions (15). Untreated cells were used as control.…”

Echinacoside suppresses pancreatic adenocarcinoma cell growth by inducing apoptosis via the mitogen-activated protein kinase pathway

“…Although it has been reported that ECH exhibits a protective role by inhibiting apoptosis and inflammatory signals in somatic cells, such as neuronal and intestinal epithelial cells (16)(17)(18)(19), it remains elusive whether ECH controls cancerous cell growth and proliferation. To test this, a cell survival assay was conducted by treating SW1990 cells, derived from a grade II pancreatic adenocarcinoma, with titrated doses of ECH as shown in Fig.…”

“…Also, ECH has been shown to have protective effects on nerve tissue and improve behavioral disorders in murine models of Parkinson's disease (18). Notably, it has been found that ECH promotes cell proliferation and inhibits apoptosis in the mouse intestinal epithelial MODE-K cells (19). Thus far, however, less attention has been paid to the potential role of ECH in cancer prevention.…”