Table 2.
The effect of baicalein on inflammatory bowel disease and colorectal cancer.
| Disease | Animal/Cell Models | Dose and Times | Up-Regulation | Down-Regulation | Refs. |
|---|---|---|---|---|---|
| UC | DSS-induced UC mice | 25 mg/kg, 7 days | IκBα | COX-2, iNOS, cyclin D1, p-IκBα, p-p65, p65, IKKβ, NF-κB, p-STAT3, STAT3 |
[85] |
| 20 mg/kg, 10 days |
IL-4 | IFN-γ | [116] | ||
| 40 mg/kg, 10 days |
CYP1A1 | IL-6, IL-10, IL-17, IL-22, TNF-α, TNF-β | [117] | ||
| 20 mg/kg, 13 days |
CDX2, MDR1 (colon), Cyp3a11 (colon) | TNF-α, IL-6 | [100] | ||
| UC rats of various complex factors | 100 mg/kg, 7 days | SOD, ATP | AST, ALT, GGT, TG, MDA, NO, cAMP/cGMP, IL-6, IL-1β, IL-17, NF-κB p65, p38 | [107] | |
| CD | TNBS-induced CD mice | 20 mg/kg/d, 10 days | iNOS, ICAM-1, MCP-1, COX-2, TNF-α, IL-1β, TLR4, MyD88, p-p65, p-IκBα, p-p38 | [118] | |
| CRC | HCT116 cells | 60 µM, 48 h |
apoptosis, caspase-3 and - 9 | [119] | |
| 100 µM, 24 h | cleavage of PARP, PPARγ | pro-caspase-3, -8, and -9, p-IκBα, iNOS, p50 (nuclear), p65 (nuclear), MMP-2 and -9 | [120] | ||
| 40 µM, 4 h |
p-Nrf2/Nrf2 | [121] | |||
| 40 µmol/L, 24 or 48 h | p53, p21 | Ezrin, cyclin D1, CDK4 | [122] | ||
| HCT116, A549, and Panc-1 cells | 40 µM, 48 h | apoptotic rate, cleaved of caspase-3 and -9, DEPP, GADD45A, p-JNK, p-ERK, p-p38 | [123] | ||
| HCT116, SW480, and HT29 cells | 20 µM, 72 h | apoptotic cells, hTERT, p-ERK, p-p38 | [89] | ||
| HT29 cells | 100 µM, 48 h | cleavage of PARP and caspase-3, Bax, p53 |
Bcl-2, p-AKT, p-caspase- 9, p-GSK-3β, survivin, cyclin D1, cyclin B1 |
[124] | |
| HT29 xenograft | 10 mg/kg three times/week, 43 days | apoptotic cells, p53, p21 | [124] | ||
| LS174T cells | 25 µM, 48 h | PXR, CDX2 | [100] | ||
| DLD-1 cells | 30 µM, 24 h | MMP-2 and -9, p-AKT | [125] | ||
| HT29 and DLD1 cells | 30 µM, 24 h | MMP-2 and -9, p-ERK | [126] | ||
| DLD1 xenograft | 20 mg/kg/day, 21 days | MMP-2 and -9, p-ERK | [126] | ||
| HCT116 xenograft | 50 mg/kg, 3 weekly cycle | Ki67 | [122] | ||
| Miscellaneous | RAW 264.7cells (LPS-treated) | 50 μM, 2 h or 48 h | TLR4, MyD88, IRAK-1, COX-2, NO, iNOS, p-JNK, p-ERK1/2, p-p38, MD-2/TLR4 |
[118] | |
| 80 μM, 2 h | p-ERK, p-p38, p-JNK, p- JAK1, p-JAK2 | iNOS, TNF-α, IL-6, IL-1β, NO, PGE2, p-STAT1(Tyr701), p-STAT3(Tyr705), p-STAT3(Ser727) | [127] | ||
| 10 μM, 2 h | TNF-α, COX-2, iNOS, NO, IL-1β, PGE2, p-IκBα |
[128] | |||
| RAW 264.7 cells (polyinosinic–polycytidylic-acid-treated) | 100 µM, 24 h | NO, calcium release, IL-1α, IL-6, G-CSF, GM-CSF, VEGF, MCP-1, IP-10, LIX, RANTES, STAT1, LIX, STAT3, CHOP, Fas |
[129] | ||
| THP-1 cells (LPS-treated) | 50 μM, 2 h | iNOS, COX-2, IL-1α, IL-1β, NLRP3, ASC, caspase-1 | [118] | ||
| EL-4 cells | 50 μM, 24 h | CYP1A1, AHR (nuclear) | AHR (cytosol) | [117] | |
| colonic lamina propria lymphocyte | 40 mg/kg, 10 days |
CD4+CD25+Foxp3+ T cells | CD4+IL-17+ T cells | [117] | |
| mesenteric lymph of mice | 40 mg/kg, 10 days |
CD4+CD25+Foxp3+ T cells | CD4+IL-17+ T cells | [117] |
AHR, aryl hydrocarbon receptor; AKT, protein kinase B; ALT, alanine aminotransferase; ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; AST, aspartate aminotransferase; ATP, adenosine triphosphate; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma-2; cAMP, cyclic adenosine monophosphate; CD, Crohn’s disease; CDK4, cyclin-dependent kinase4; CDX2, caudal-type homeobox 2; cGMP, cyclic guanosine monophosphate; CHOP, C/EBP-homologous protein; COX-2, cyclooxygenase-2; CRC, colorectal cancer; CYP1A1, Cytochrome P450, family 1, subfamily A, polypeptide 1; DEPP, decidual protein induced by progesterone; DSS, dextran sulfate sodium; ERK, extracellular signal-regulated kinase; GADD45A, growth arrest and DNA-damage-inducible 45 alpha; G-CSF, granulocyte colony-stimulating factor; GGT, γ-glutamyl transpeptidase; GM-CSF, granulocyte macrophage colony-stimulating factor; GSK-3β, glycogen synthase kinase-3 beta; hTERT, human telomerase reverse transcriptase; ICAM-1, intercellular adhesion molecule-1; IFN-γ, interferon gamma; IKKβ, inhibitor of nuclear factor kappa-B kinase subunit beta; IL-, interleukin; iNOS, inducible nitric oxide synthase; IRAK-1, inhibition of interleukin-1 receptor-associated kinase 1; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; p-, phosphorylation; JAK, Janus protein tyrosine kinase; JNK, c- Jun N-terminal kinase; LIX, lipopolysaccharide-induced CXC chemokine; LPS, lipopolysaccharide; MCP-1, monocyte chemotactic protein-1; MDA, malondialdehyde; MDR1, multidrug resistance protein 1; MD-2, myeloid differentiation protein-2; MMP, matrix metalloproteinase; MyD88, myeloid differentiation factor 88; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NO, nitric oxide; NLRP3, nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3; Nrf2, nuclear factor erythroid-2-related factor 2; RANTES, regulated upon activation, expressed by normal T cell and presumably secreted; p-, phosphorylation; PARP, poly(ADP-ribose) polymerase; PGE2, prostaglandin E2; PPARγ, peroxisome proliferator-activated receptors γ; PXR, pregnane X receptor; RANTES, chemokine ligand 5; SOD, superoxide dismutase; STAT, signal transducer and activator of transcription; TNF, tumor necrosis factor; TLR4, toll-like receptor 4; TNBS, trinitrobenzene sulphonic acid; TG, triglyceride; VEGF, vascular endothelial growth factor; UC, ulcerative colitis.