Genistein-modified poly(amide):poly(vinyl pyrrolidone) (PA:PVP/G) hemodialysis membranes have been fabricated by coagulation via solvent (dimethyl sulfoxide, DMSO)/nonsolvent (water) exchange. The antioxidant and anti-inflammatory properties of the unmodified PA:PVP membranes were evaluated in vitro using human blood. It was found that these unmodified PA:PVP membranes were noncytotoxic to peripheral blood mononuclear cells (PBMC) but raised intracellular reactive oxygen species (ROS) levels. Pure genistein (in DMSO solution) was not only nontoxic to PBMC, but also suppressed the ROS levels in a manner dependent on genistein dosage. A similar dose-dependent suppression of ROS was found in genistein-modified PA (i.e., PA/G) membranes. However, the PVP addition had little or no effect in the suppression of ROS levels for the ternary PA:PVP/G system; the membrane ROS suppression was largely controlled by the genistein dosage. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin (IL-6) in whole blood were measured by ex vivo stimulation with lipopolysaccharide (LPS). The unmodified PA:PVP membranes drastically increased the level of TNF-α; however, the concentration of IL-1β and IL-6 remained almost the same. The PA/G membranes reduced the concentration of IL-1β and TNF-α even at very low genistein loadings, but it required a higher genistein loading to realize a similar effect in the case of IL-6. Of particular importance is that the genistein-modified blend membranes (PA:PVP/G) showed greater suppression of the concentrations of all three cytokines (TNF-α, IL-1β, and IL-6) in comparison with those of the PA/G membranes, signifying the role of PVP in the enhanced anti-inflammatory properties of these genistein-modified membranes. Ultraviolet-visible (UV-vis) spectroscopy was employed to quantify any genistein leaching during the in vitro testing.

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By virtue of antioxidant and anti-inflammable properties, plant-derived phytochemicals such as mangiferin and genistein have attracted considerable attention for functionalization of polymeric hemodialysis (HD) membranes via solution blending. In-vitro dihydrorhodamine (DHR) assay of the genistein-modified membranes revealed drastic reduction in the level of the reactive oxygen species (ROS). In contrast, mangiferin-modified HD membrane manifested the pro-oxidant activity. We suspected that such difference in ROS generation may be attributed to the glucose unit on the xanthone backbone of mangiferin. This hypothesis was confirmed by comparing the ROS levels of genistein versus genistin, and mangiferin versus xanthone and 3,4,5,6-tetrahydroxyxanthone. Phytochemicals without the glucose unit show better antioxidant property related to the glycosides. Anti-inflammatory property was further conducted by measuring the level of TNF-α in blood after contacting with the same selected phytochemicals. Of particular interest is that the glucose unit promotes the generation of TNF-α.

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