## 4 Discussion
### Antioxidant and Anti-Inflammatory Pathways Targeted by Phytochemicals for the Treatment of IBD
Anthocyanins that have anti-inflammatory and antioxidant properties seem to attenuate the course of colitis in animal models [115; 116; 117]. Macrophages and neutrophils produce ROS in the inflamed bowel in IBD. The antioxidant system of the intestine is overwhelmed and thus potential antioxidants, such as anthocyanin rich compounds, have been investigated for their potential therapeutic effect. Resveratrol, a polyphenolic flavonoid substance, has antioxidant and anti-inflammatory effects as verified by experimental models for colitis, where oxidant/antioxidant balance appears to play an important role in pathogenesis [118]. Several articles indicate that resveratrol decreases oxidative stress, increases antioxidant enzyme concentration in tissues and decreases inflammatory biomarkers in animal models of UC [119]. Other experimental studies showed that resveratrol reduces colonic tissue malondialdehydedehyde and myeloperoxidase-base but increases superoxide dismutase (SOD) and glutathione peroxidase (GPX) activity while it inhibits collagen I synthesis in IGF-1-stimulated fibroblasts [120; 121]. Polyphenylon E--EGCG is a part of the catechin family of polyphenols contained in green tea. This family of phytochemicals has been extensively studied in regard to anti-inflammatory and antineoplastic effects due to its potent antioxidant properties. EGCG has an effect in preventing NF-kB nuclear translocation by the inactivation of IkB kinase. This suppresses production of cytokines, inflammatory enzymes and inflammatory protein kinases while upregulating anti-inflammatory pathways [122; 123]. Procyanidins and other phenols in Pycnogenol(r) display various biomodulating, anti-neoplastic and antioxidant effects such as inhibition of NF-kB and cyclooxygenase stimulated of nitric oxide (NO) synthase and antihypertensive effect by inhibition of angiotensin-converting enzyme [124; 125; 126]. It was shown that it increased SOD and GPX antioxidant enzymes while it reduced oxidative damage to proteins and lipids. It also increased DAO after 5 and 10 weeks of Pycnogenol(r) administration. DAO is found primarily in the mucosa of the gut and is a marker of histamine intolerance and also of disease activity. It inversely correlates with small intestine barrier permeability [51]. Silybinin is the main component of silymarin flavonalignans, the extract of a species of thistle (_Silibum marianum_). Reports from experimental murine and rat models of colitis provide evidence for immune-mediated intestinal wall healing with reduction in TNF-a, NF-kB and intereleukin-1b and also in disease activity [127; 128; 129]. Tormentil extract contains tannins, mainly agrimonin, pedunculagin, laevigatin B and F found in the _Tormentillae rhizoma_. The mechanisms of its actions are not fully understood. However, tannins are known to promote wound healing and they have anti-inflammatory and anti-secretory results while their antibacterial properties may regulate the gut microbiota [46]. T2 is a chloroform/methanol extract of _Triptergyium wilfordii_ containing tritptolide. It is used in China for a variety of immune mediated disorders such as rheumatoid arthritis. Triptolide inhibition of NF-kB and TNF-a signaling pathways, suppression of IL-6/STAT3 signaling pathway and down-regulation of IL-17 has been proven in experimental animal models of colitis [130; 131; 132]. Regulatory T-cells modulate the immune response in the intestine by secretion of inhibitory cytokines such as IL-10 and transforming growth factor-b (TGF-b). Their disruption can affect CD and T2 can upregulate Foxp+ CD4+ T-Cells [52]. It should be mentioned that the safety of _Triptergygium wilfordii Hook [PERSON]_ remains a matter of significant debate and ongoing research [133]. Eacbept sodium is a pine resin derivative phytochemicalonical. Its anti-inflammatory effects are thought to come from its affinity to adhere to gastric mucosa, epithelial cells and ulcer regions.