Table 2.
Other examples of targeted apoptosis for the treatment of IBD
| Therapeutic strategies | Type of condition (s) | Targets | Mechanism of action | Reference |
|---|---|---|---|---|
| S1P receptor 1 and 5 agonist (ozanimod) | UC | NF-κB, TNF-α | S1P, a protein similar to TNF-α, activates NF-κB, triggering inflammation and immune responses. Ozanimod reduces inflammation by binding to S1P receptors 1 and 5. | [163] |
| LR | UC | Th17/Treg cells, JAK-STAT signaling pathway | LR ethanol extract fights UC by balancing Th17 and Treg cells. LRWE reduces inflammation and apoptosis by inhibiting the JAK-STAT signaling pathway by lowering p-JAK2, p-STAT3, Bcl-2, and BAX protein expression. | [164] |
| Si Shen Wan | UC | PLC-γ1, PI3K/AKT signaling pathway | SSW inhibits apoptosis in IECs by activating PLC-γ1 and inhibiting AKT phosphorylation, thereby inhibiting the PI3K/AKT signaling pathway. | [165] |
| THP | UC | TNF-α, SOCS1/JAK2/STAT3 signaling pathway | THP downregulates pro-inflammatory cytokines IL-6, TNF-α, and IL-17 and enhances forkhead box protein P3 expression. It also modulates the SOCS1/JAK2/STAT3 pathway and supports the intestinal mucosal barrier. | [166] |
| Probiotics (LP082) | UC | TNF-α, NF-κB pathway | The probiotic LP082 protects the intestinal mucosal barrier, reduces inflammation, and regulates microbial imbalance by inhibiting TNF-α and the NF-κB pathway. | [167] |
| Fuzi-ganjiang herb | UC | MAPK, NF-κB and STAT3 signaling pathway | The fuzi-ganjiang combination shows notable anti-inflammatory effects in DSS-induced UC mice, possibly inhibiting MAPK, NF-κB, and STAT3 signaling pathways. | [168] |
| GQ | UC | IL-6/JAK2/STAT3 signaling, Treg and Th17 cell | GQ alleviated DSS-induced UC by suppressing IL-6/JAK2/STAT3 signaling to restore Treg and Th17 cell homeostasis in colonic tissue. | [169] |
| Daphnetin | UC | JAK2/STAT3 signal, Bcl-2 family proteins, caspase | Daphnetin acts in UC via REG3A-activated JAK2/STAT3 signaling, increasing anti-apoptotic protein Bcl-2 and reducing pro-apoptotic proteins BAX and cleaved caspase 3. | [170] |
| Fufangxiaopi formula (FF) | UC | TLR4/NF-κB and MAPK signaling pathways | FF inhibits pro-inflammatory reactions and reduces TNF-α, iNOS, IL-6, IL-1β, and COX-2 production by blocking TLR4/NF-κB and MAPK signaling in RAW264.7 cells. | [171] |
| MBP | UC | NF-κB | MBP alleviates DSS-induced UC by inhibiting the TLR4/MAPK/NF-κB signaling pathway and modulating the gut microbiota. | [172] |
| Licorice | UC | NF-κB signaling pathway | Licorice reduces inflammation, strengthens the gut mucosal barrier via the TLR4/MyD88/NF-κB regulatory route, and balances T helper cell development. | [173] |
| DZT | UC | NF-κB, STAT3/5 pathway | Mitigates UC by targeting IKKα/β and JAK2 kinases to block the NF-κB and STAT3/5 pathways. | [174] |
| ISO | CD | AMPK/PGC1α signaling pathway, caspase, Bcl-2 protein family | The ISO moiety activates the AMPK/PGC1α pathway, reducing apoptotic IECs by lowering cleaved-caspase-3/caspase-3 and BAX levels while increasing Bcl-2. This alleviates TNBS-induced intestinal barrier dysfunction and CD-like colitis in mice. | [175] |
| Curcumin | UC, CD | NF-κB, TNF-α, p38MAPK | Curcumin effectively inhibits inflammation by blocking TNF-α-mediated NF-κB activity and reducing inflammatory activity by decreasing p38 MAPK activity. | [176,177] |
| MPST | UC, CD | PI3K/AKT pathway | MPST directly interacts with AKT, reducing its phosphorylation and overexpression, decreasing caspase-3 protein levels, increasing BCL-xL protein levels, and inhibiting IEC apoptosis. | [178] |
| The JAK inhibitor (Tofacitinib) | UC, CD | JAK-STAT signaling pathway | Tofacitinib inhibits JAK1 and JAK3 signal transduction pathways, reducing inflammatory responses and preventing apoptosis. | [179] |
| OPEN | UC, CD | P53 | PFT-α, an inhibitor of P53, effectively reduces excessive apoptosis in IECs. | [10] |
Abbreviations: IBD, Inflammatory bowel disease; UC, Ulcerative colitis; CD, Crohn disease; S1PR, Sphingosine 1-phosphate receptor; MAPK, Mitogen-activated protein kinase; MPST, 3-mercaptopyruvate sulfurtransferase; PI3K, Phosphatidylinositol 3-kinase; AKT, Protein kinase B; IEC, Intestinal epithelial cell; JAK, Janus kinase; STAT, Signal transducer and activator of transcription; LR, Linderae Radix; LRWE, LR aqueous extract; PLC-γ1, Phospholipase C gamma1; THP, Tetrastigma hemsleyanum polysaccharide; SOCS1, Suppressor of cytokine signaling1; LP082, Lactobacillus plantarum HNU082; DSS, Dextran sodium sulfate; GQ, Gegen Qinlian decoction; IL-6, Interleukin 6; REG3A, Regenerating protein 3 alpha; TLR, Toll-like receptor; FF, Fufangxiaopi formula; iNOS, Inducible nitric oxide synthase; COX-2, Cyclooxygenase-2; MBP, Mesona chinensis Benth polysaccharides; MyD88, Myeloid differentiation factor-88; DZT, Demethylzeylasteral; IKK, Inhibitor kappa B kinase; ISO, Isongifolene; AMPK, AMP-activated protein kinase; PGC1α, Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha; TNBS, 2,4,6-trinitrobenzene sulfonic acid; OPEN, Oral pifithrin-α embedded nanomedicine; PFTα, Pifithrin-α.