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A critical review of Astragalus polysaccharides: From therapeutic mechanisms to pharmaceutics
As the important active ingredients of Astragali Radix (AR), Astragalus polysaccharides (APs) have therapeutic potential for multiple diseases including nervous system diseases, cardiovascular diseases, diabetes mellitus, and cancer. A large number of cell experiments combined with animal experiments have shed light on the therapeutic mechanisms and therapeutic effects of APs on a variety of diseases. However, the clinical application of APs is not widespread, except for the use of injected APs in the clinical adjuvant therapy of cancer. Due to the excessive molecular weight, bulky, low solubility and negatively charged characteristics, APs have low bioavailability which limits their clinical application. With the deepening of researches on the pharmaceutics of APs, the nanocrystals and moderate structural modification enormously boost the bioavailability, which may expand the application of APs. This review summarizes the studies in pharmacodynamic properties and pharmaceutics of APs, with the purpose of providing experimental researches and clinical application data for expanding the clinical development through expounding the therapeutic mechanisms and pharmaceutical researches of APs.
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Effects of Selenized Astragalus Polysaccharide on the Adhesion and Endocytosis of Nanocalcium Oxalate Dihydrate after the Repair of Damaged HK-2 Cells
An oxidative damage model of human proximal renal epithelial cells (HK-2) was established using oxalate damage. The repair effects of Astragalus polysaccharide (APS) and selenized APS (Se-APS) on damaged HK-2 cells were investigated. Differences in the adhesion and endocytosis of HK-2 cells to calcium oxalate dihydrate crystals with a size of approximately 100 nm before and after APS and Se-APS repair were also explored. The results showed that after being repaired by APS and Se-APS, HK-2 cells exhibited increased cell viability, restored cell morphology, reduced reactive oxygen species level, increased mitochondrial membrane potential, reduced phosphatidylserine eversion, and osteopontin expression. Moreover, the amount of adherent crystals on the cell surface decreased, but the amount of endocytic crystals increased. At the same concentration, Se-APS exhibited better repair effects on the damaged HK-2 cells than APS. All these findings revealed that Se-APS may be a potential drug candidate for inhibiting the formation of kidney stones.
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Comparison of the adhesion and endocytosis of calcium oxalate dihydrate to HK-2 cells before and after repair by Astragalus polysaccharide
This work investigated the effects of repairing injured renal proximal tubular epithelial (HK-2) cells by using three Astragalus polysaccharides (APS) with different molecular weights and the adhesion and endocytosis of HK-2 cells to the calcium oxalate dihydrate (COD) nanocrystals before and after repair to develop new products that can protect against kidney stones. HK-2 cells cultured in vitro were injured with 2.6 mmol/L oxalic acid to establish a damaged cell model. Three kinds of APS (APS0, APS1, and APS2 with molecular weights of 11.03, 4.72, and 2.60 kDa, respectively) were used to repair the damaged cells. The changes in the adhesion and endocytosis of 100 nm COD crystals to cells before and after the repair were detected. After the repair of HK-2 cells by the APS, the speed of wound healing of the damaged HK-2 cells increased, and the amount of phosphatidylserine (PS) ectropion decreased. In addition, the proportion of cells with adhered COD crystals decreased, whereas the proportion of cells with internalized crystals increased. As a result of the repair activity, APS can inhibit the adhesion and promote the endocytosis of COD nanocrystals to damaged cells. APS1, which had a moderate molecular weight, displayed the strongest abilities to repair the cells, inhibit adhesion, and promote endocytosis. Thus, APS, particularly APS1, may serve as potential green drugs for preventing kidney stones.
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Preparation and characterization of selenized Astragalus polysaccharide and its inhibitory effect on kidney stones
Astragalus polysaccharide (APS) was modified using the Na2SeO3/HNO3 method to obtain selenized APS (Se-APS) with a selenium content of 1.75 mg/g. The structure and physicochemical properties of APS and Se-APS were investigated through transmission electron microscopy–energy dispersive spectroscopy mapping, fourier transform infrared spectroscopy, nuclear magnetic resonance, nano-zetasizer analysis, atomic force microscopy, and scanning electron microscopy. APS and Se-APS did not exhibit toxic effects on human kidney proximal tubular epithelial (HK−2) cells and were able to remove hydroxyl and DPPH radicals, alleviate the damage caused by calcium oxalate (CaOx) monohydrate (COM) crystals to HK-2 cells, reduce intracellular reactive oxygen species levels, and restore cell viability and morphology. Both APS and Se-APS could inhibit COM growth, induce calcium oxalate dihydrate formation, and increase the absolute zeta potential of the crystals to inhibit crystal aggregation. However, the ability of Se-APS to regulate CaOx crystals and protect the cells from COM-induced damage was better than that of APS. These results suggested that Se-APS might be a candidate drug for the treatment and prevention of kidney stones.
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Repair Effects of Astragalus Polysaccharides with Different Molecular Weights on Oxidatively Damaged HK-2 Cells
This study investigated the repair effects of three Astragalus polysaccharides (APSs) with different molecular weights (Mws) on injured human renal proximal tubular epithelial (HK-2) cells to reveal the effect of Mw of polysaccharide on cell repair. A damage model was established by injuring HK-2 cells with 2.6 mM oxalate, and APS0, APS1, and APS2 with Mw of 11.03, 4.72, and 2.61 KDa were used to repair the damaged cells. After repair by APSs, the morphology of damaged HK-2 cells gradually returned to normal, the destruction of intercellular junctions recovered, intracellular reactive oxygen species production amount decreased, and their mitochondrial membrane potential increased. In addition, the cell cycle progression gradually normalized, lysosome integrity increased, and cell apoptotic rates obviously declined in the repaired cells. All three APSs could promote the expression of Keap1, Nrf2, SOD1, and CAT. In addition, the expression levels of inflammation markers containing MCP-1 and IL-6 decreased after APS repair. We deduced that APSs exert their repair function by activating the Nrf2–Keap1 signaling pathway and inhibiting inflammation. Among the APSs, APS1 with a moderate Mw provided the strongest repair effect. APSs may have a preventive effect on kidney stones.
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