Table 2 Pharmacotherapy for IBD

Aminosalicylates (5-aminosalicylates,Sulphasalazine, Olsalazine)

eIF4b, eIF4e

(a) Scavenging reactive oxygen species

^{98, 99}

(b) Upregulation of endogenous antioxidant systems

(c) Altering faecal bacteria profiles and exerting anti-inflammatory activities by inhibition of leukocyte motility

(d) Inhibiting tetrahydrobiopterin biosynthesis and NO formation

(e) Preventing mitochondrial damage by inhibition of phosphatidic acid formation and phosphatidylethanolamine degradation, and alteration of mitochondrial lipid composition

(f) Interfering with TNF-α, TGF-β, NF-κB and IL-1

(g) Suppressing the proliferation of human colon cancer cells and by inhibiting MMP-2 and MMP-9 expression via NF-κB-mediated cell signals and invasiveness

(h) Interacting with the Wnt/β-catenin pathway via inhibition of PP2A and with the active center of tumor suppressor PPAR-γ

(i) Arresting colon epithelial cells in S-phase by the activation of an ATR-dependent checkpoint and improving replication fidelity

(j) Down-regulation of expression of endostatin and angiostatin by modulation of MMP2 and MMP9 via inhibition of TNF-α

Glucocorticoids (Budesonide, Hydrocortisone, Prednisolone)

undetermined

(a) Steroid-activated GR binds to glucocorticoid-responsive elements, resulting in modulation of antiinflammatory transcriptional pathways such as NF-κB, annexin1 and MAPK.

¹⁰⁰

(b) GR can decrease the expression of proinflammatory genes directly by protein–protein interactions.

(c) Glucocorticoids ameliorate ER stress in intestinal secretory cells by promoting correct protein folding and enhancing degradation of misfolded proteins.

Immunomodulators (6-mercaptopurine, azathioprine, methotrexate)

undetermined

(a) Formation of thioguanine nucleotides leads to inhibition of DNA, RNA and protein synthesis, and induction of cytotoxicity and immunosuppression.

^{101, 102}

(b) Inducing T cell apoptosis by blockade of Rac1 activation upon CD28 co-stimulation and suppressing MEK, NF-κB, and bcl-xl

(c) Methotrexate competitively binds to folic acid in combination with dihydrofolate reductase, interfering with DNA synthesis and leading to cell death.

(d) Decreasing pro-inflammatory cytokine production and induction of lymphocyte apoptosis

Antibiotics (Flagy, Ciprofloxacin, Cephalosporins)

undetermined

(a) Altering composition of intestinal bacteria, reducing harmful bacteria and promoting the growth of probiotics to reduce inflammation

^{103, 104}

(b) Reducing bacterial invasion of surrounding tissues in the intestinal lumen, and bacterial migration and systemic dissemination

Biological agents (Infliximab, Adalimumab, Etanercept)

TNF-α

(a) Neutralizing the biological activity of TNFα by binding to the soluble and transmembrane forms of TNFα with high affinity, preventing it from binding to cellular receptors and inducing the lysis of cells

^{105, 106}

(b) Restoring the gut barrier, preventing leukocyte infiltration in intestinal mucosa and reducing the expression of β7 and CCR7 in leukocytes, thereby inhibiting inflammation

(c) Incurring apoptosis of T lymphocytes and mononuclear macrophage