# Phytoglycoproteins and Human Health: Current Knowledge and Future Applications
## 3 Bioactive Properties of Phytoglycoproteins
### Antioxidant and Chemoprotective Properties  
Some PGPs possess direct or indirect antioxidant effects in cells. Considering that the effects of hepatotoxins are initiated through oxidative and inflammatory damages, many agents with antioxidant and anti-inflammatory properties are believed to exert hepatoprotective effects. In a chemically-induced, cellular injury generated by 12-O-tetradanoylplirborbol 13-acetate (TPA), a toxicant that initiates tumor formation by enhancing oxidative stress and activating PKC and iNOS signaling pathways, the chemo-preventative potential of UDP glycoprotein with radical scavenging properties was demonstrated in NIH/3T3 cells. [PERSON] et al. [47] reported that PGPs at 100 \(\mathrm{\SIUnitSymbolMicro g}\)/mL blocked the activation of PKC and NF-kB, nitric oxide release and apoptosis in the oxidant-challenged NIH/3T3 cells. Furthermore, PGPs exhibited hepatoprotective effects by protecting the hepatic membrane against oxidative damage and leakage of intrahepatic enzymes into circulation, reducing ROS formation and gene expression of NF-kB and AP-1, and boosting the activities of antioxidant enzymes and nitric oxide production in models of acute liver injury [48; 49]. Additionally, UDP glycoprotein suppressed was shown to increase nitric oxide level and activities of (superoxide dismutase (SOD)), CAT and GPx in Triton WR-1339-treated mouse [50], signifying the robust antioxidant and cellular-protective potentials of UDP glycoproteins in many models of oxidative stress. Similarly, SNP glycoprotein was shown to protect MCF-7 cells from TPA-generated cytotoxicity by inhibiting DNA binding of AP-1 and NF-kB and preventing apoptosis [51]. Glucose/glucose oxidase (G/GO) system induces intracellular ROS production leading to cytotoxicity, and is hence used as a study model for investigating the cellular antioxidant property of compounds. After observation of ferric ion-chelating activities, [PERSON] and co-workers [9] reported that _Gardenia jasminoides_ (GPG) glycoprotein suppressed ROS production and cytotoxicity in BNL CL2 cells subjected to G/GO oxidative challenge. The authors also showed that GPG glycoprotein at 80 mg/kg suppressed the formation of Thiobarbituric acid reactive substances (TBARS) and leakage of hepatic lactate dehydrogenase (LDH) into circulation whereas it improved nitric oxide production and hepatic antioxidant enzyme activities in carbon tetrachloride-challenged mice by suppressing hepatic cytochrome \(c\), NF-kB and AP-1 gene expression. In another study, ZPFG glycoprotein was reported to possess excellent radical scavenging activities against superoxide anion and hydroxyl radicals, and suppressed oxidation-mediated cytotoxicity generated by hypoxanthine/xanthine oxidase and G/GO systems in Chang liver and BNL CL2 ( murine liver) cell lines [52]. The authors further demonstrated that ZPFG glycoprotein (20 mg/kg) protected mouse hepatocytes from carbon tetrachloride-induced acute hepatotoxicityicity by suppressing the leakage of hepatic enzymes (LDH and alanine aminotransferase (ALT)) into circulation, and reducing the formation of TBARS in serum, as well as boosting of hepatic antioxidant status (SOD, CAT and GPx activities). Based on previous knowledge that antioxidant mechanism is involved in hepatoprotection, PGPs were demonstrated that ZPFG glycoprotein (50 uM in cultured hepatocytes and 10 mg/kg in ICR mice) exhibited hepatocyte effect by reducing circulating ALT and LDH, suppressing ROS production by downregulating gene expression profiles of heme oxygenase and metallothione, and enhancing the activities of hepatic SOD, CAT and GPx in heavy metal-induced hepatotoxicityicity [5]. In addition, ZPFG glycoprotein inhibited the production of inflammatory mediators (prostaglandins, nitric oxide and pro-inflammatory cytokines) in hepatocytes through the downregulation of ERK, p38 MAPK, COX-2, iNOS, AP-1 and Nrf-2 gene expression [53].