RESUMO
Renal fibrosis is the final common result of a variety of progressive injuries leading to chronic renal failure. However, there are no effective clinical available drugs for the treatment. Notoginsenoside from Panax notoginseng could ameliorate renal fibrosis. We hypothesized that polysaccharide from this herb might have similar bioactivity. Here, we elucidated structure of a novel pectin-like polysaccharide designed SQD4S2 with a netty antenna backbone of glucogalacturonan substituted by glucoarabinan, glucurogalactan and galactose residues from this herb. Interestingly, SQD4S2 could reverse the morphological changes of human renal tubular HK-2 cells induced by TGF-ß. Mechanism study suggested that this bioactivity might associate with N-cadherin (CDH2), Snail (SNAI1), Slug (SNAI2) depression and E-cadherin (CDH1) enhancement. In addition, SQD4S2 could impede critical fibrogenesis associated molecules such as α-SMA, fibronectin, vimentin, COL1A1, COL3A1, FN1 and ACTA2 expression induced by TGF-ß in HK-2 cells. Current findings outline a novel leading polysaccharide for against renal fibrosis new drug development.
Assuntos
Nefropatias/metabolismo , Túbulos Renais/metabolismo , Panax notoginseng/química , Pectinas/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Actinas/metabolismo , Caderinas/metabolismo , Linhagem Celular , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibronectinas/metabolismo , Fibrose/metabolismo , Humanos , Rim/metabolismo , Rim/patologia , Pectinas/análise , Pectinas/química , Vimentina/metabolismoRESUMO
A galactan ROH05 was isolated from the roots of Ophiopogon japonicus and further purified by DEAE Sepharose™ Fast Flow columns. The molecular weight of ROH05 was estimated to be 16.7kDa. ROH05 was composed of galactose only. According to the methylation analysis and the results of IR and NMR spectra, the backbone of ROH05 was composed of 1, 4-linked ß-D-galactose and 1, 4, 6-linked ß-D-galactose, while the branch of this polysaccharide was terminal-linked ß-D-galactose attached at C-6 position of 1, 4-linked ß-D-galactose directly. The acetylated galactan, ROH05A was prepared by the acetic anhydride-pyridine method. The acetylation modification mainly occurred at C-2, C-3 and C-6 positions of 1, 4-linked ß-D-galactose, and C-6 position of terminal-linked ß-D-galactose. Bioactivity test showed that ROH05A might inhibit both BxPC-3 and PANC-1 pancreatic cancer cells growth in a dose-dependent manner without significant toxicity to LO2 cells. In addition, the cells apoptosis was triggered since cleaved caspase-3 and FasL were activated while p53, p21, Bax expression were up-regulated by ROH05A as well.