Structure Characterization And Bioactivity Evaluation Of Polysaccharides From Dictyophora Indusiata And Its Application In Functionalization Of Anticancer Drugs

Dictyophora indusiata, a saprophytic fungus belongs to the Phallaceae Corda family, is widely distributed in Guizhou, Yunnan, Sichuan, Jiangxi and Fujian provinces of China. Dictyophora indusiata is an edible and medicinal mushroom with desirable ?avour and nutritional properties. In this study, the purification, structure characterization, immune and anti-hemolytic activities of polysaccharide from Dictyophora indusiata were investigated. Meanwhile, the Dictyophora indusiata polysaccharide DP1 was functional modificated by preparations of DP1-Se NPs and DP1-Zn complexes. The antitumor mechanism of DP1-Se NPs and DP1-Zn complexes were also studied. The results were listed as follows:Two fractions, DP1 and DP2 were isolated from the fruiting body of Dictyophora indusiata using water extraction method. Chemical Structure characterization revealed that DP1 had molecular weight of 1,132 k Da. The Chemical composition of DP1 was consisted of glucose(56.2%), galactose(14.1%) and mannose(29.7%). The main linkage types of DP1 were proved to be(1â†'3)-linked α-L-Man,(1â†'2, 6)-linked α-D-Glc,(1â†'6)-linked β-D-Glc,(1â†'6)-linked β-D-Gal and(1â†'6)-linked β-D-Man.DP1 showed notable immunomodulatory activity by enhancing macrophage NO, TNF-α and IL-6 secretion. CR3 was confirmed to be one of the specific membrane receptors of DP1 on RAW264.7. The PI3K/Akt/MAPK/NF-κB signaling pathways are the possible mechanism of the immunomodulatory activity of DP1. Furthermore, DP1 exhibited excellent thermostability and acid-base stability across broad spectrum of thermal and p H treatment.DP1 also show protective effect against oxidative hemolysis induced by AAPH. DP1 could effectively inhibit AAPH-induced overproduction of reactive oxygen speciesand alleviated the enhancement of intracellular antioxidant enzymes(superoxide dismutase [SOD]; glutathione peroxidase [GPX], andcatalase [CAT]) activities. Meanwhile, the intracellular malondialdehyde(MDA) formation were also inhibited by DP1 treatment. The formation of conjugated diene induced Cu Cl2 in plasma was significantly inhibited by DP1.Selenium nanoparticles(Se NPs) were made functional using DP1 in a redox system that included ascorbic acid(Vc) and sodium selenite. The resulting DP1-Se NPs were highly stable, homogeneous and monodispersed with an average diameter of 89 nm. DP1-Se NPs showed significant antiproliferative activity on a group of selected human cancer cell lines by induction of apoptosis. The suggested mechanisms of the pro-apoptosis activity of DP1-Se NPs were main through death-receptor and mitochondria-mediated apoptotic pathways, associated with the activation of caspases 3, 8, 9 and the Fas-associated death domain protein(FADD) along with ROS overproduction and mitochondrial dysfunction.DP1 was successfully chelated with zinc acetate to achieve its enhanced antiproliferative activity. The obtained DP1-Zn complex showed significant antiproliferative activity on a group of human cancer cell lines through induction of apoptosis. The pro-apoptotic action of DP1-Zn were confirmed by morphological changes including chromatin condensation, DNA breakage and S phase cell cycle arrest in human breast adenocarcinoma cells(MCF-7). Our study suggested that DP1-Zn can be developed as a candidate for cancer treatment and prevention, especially human breast adenocarcinoma.Our study indicated that DP1 was an ideal complementary medicine or functional food for therapeutics of hypoimmunity and oxidative stress-related diseases diseases. DP1-Se NPs and DP1-Zn complexes are the functional materials with notable beneficial potency and relatively low toxicity. These two complexes provided new materials and research ideas for the design of anticancer drugs and have broad application prospects in the field of biomedicine.