# Phytoglycoproteins and Human Health: Current Knowledge and Future Applications
## 3 Bioactive Properties of Phytoglycoproteins
### Anti-Inflammatory and Immunomodulatory Properties  
PGPs have demonstrated anti-inflammatory effects in endotoxin-induced inflammation. Lipopolysaccharides (LPS) stimulate inflammation via activation of NF-\(\kappa\)B and other inflammation signaling pathways, leading to upregulation of gene expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and pro-inflammatory cytokines such as interleukins and tumor necrotic factor (TNF)-\(\alpha\). A 36-kDa phytoglycoprotein from _Rlus verniciflua_ STOKES was reported to suppress LPS-induced inflammation in RAW 264.7 macrophages by activating protein kinase C (PKC), and suppressing intracellular ROS production and expression of NF-\(\kappa\)B and AP-1, leading to downregulation of COX-2 and iNOS gene expression [39]. Similar effects of PGPs have been reported in other inflammation models. For example, in inflammation induced by Bisphenol A, a xenoestrogen known to induce uncontrolled cell proliferation, inflammation and oxidative stress, a 30-kDa phytoglycoprotein (carbohydrate-protein ratio of 5:1) from _D. batatas_ Dene at 200 \(\upmu\)g/mL was shown to abrogate the proliferation of cultured Chang liver cells by reducing intracellular ROS and nitric oxide production through inhibition of MAPK activation, an indication of anti-inflammatory property [10]. Furthermore, the _D. batatas_ phytoglycoprotein was later reported to suppress allergic processes in cultured lymphocytes sensitized with ovalbumin by downregulating the expression of IL-4 and IL-10 while upregulating that of IFN-\(\gamma\) via blocking of GATA-3, STAT-6, p44/42 MAPK and p38 MAPK signaling pathways [4]. In another study, a 24-kDa glycoprotein from _Z. pipertium_ DC fruit inhibited the release of IL-4, histamine and immunoglobulin E in experimentally-induced allergy in mice at 10 mg/kg body weight. At lower doses, the glycoprotein inhibited the degranulation of human mast (HMC-1) cells, reduced intracellular calcium ion, and downregulated the activation of MAPK, NF-\(\kappa\)B and COX-2 signaling pathways, all of which contributed to the prevention of allergic inflammation [40]. Moreover, a 75-kDa phytoglycoprotein from _Cudrania tricuspidata_ at 100 \(\upmu\)g/mL was shown to suppress Bisphenol A-induced inflammation by inhibiting the gene expression of TNF-\(\alpha\) and IL-6 [41] and IL-4, IFN-\(\gamma\), IL-1\(\upmu\) and COX-2 [42] in cultured HMC-1 cells via blocking of NF-\(\kappa\)B and PKC/p38 kinase signaling pathways. Several other PGPs have been shown to possess anti-inflammatory properties following the above mechanisms, despite being sourced from different plant species and having varied molecular weights. This evidence suggests possible similarity in the PGPs structural motifs responsible for the bioactivity. In addition to these cellular mechanisms, PGPs from _Z. pipertium_ was also shown to in hibit c-Jun N-terminal kinase (JNK) and MMP-9 gene expression in LPS-challenged RAW 264.7 macrophages [43], suggesting multiple mechanisms of the phytoglycoprotein in abrogating inflammation. Through the mechanisms, a 75-kDa phytoglycoprotein extracted from _C. tricuspidata_ Bureau was reported to reduce pathological process of inflammatory bowel disease by stimulating signaling processes related to proliferation in colon epithelial (HT-29) cells [8]. The immunomodulatory property of PGPs was demonstrated in a study where a 38-kDa glycoprotein isolated from _Stytrax japonica_ (SJP) normalized the proliferation of cells of the immune system, phagocytic activities of macrophages, antioxidant status and gene expression profiles of IL-2, IL-12, and IFN-\(\gamma\) in cyclophosphamide-immunosuppressed mice [44]. Similarly, rice bran-derived glycoproteins were reported to stimulate immune response in cultured cells and animals. In RAW 264.7 macrophages, the rice bran PGPs stimulated the expression of iNOS and concomitant production of NO, and TNF-\(\alpha\), IL-1\(\beta\), IL-6, and IL-10 [45].