The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment
Abstract
:1. Introduction
2. TLR4 Pathway
3. TLR4 Pathway-Related Biochemical Processes
3.1. Cancer Cell Proliferation
3.2. Apoptosis
3.3. Metabolism
3.4. Inflammation and Immunization
3.5. Tumor Microenvironment
3.6. Drug Resistance
3.7. EMT/Migration/Invasion/Metastasis
4. TCMs with Anti-CRC Effects through TLR4 Signaling Pathway
4.1. The Compounds Derived from TCMs with Anti-CRC Effects through TLR4 Signaling Pathway (Table 1)
Natural Compounds | Sources | Concentration/Dosage | Major Effects | Involved Pathways | Ref. |
---|---|---|---|---|---|
Andrographolide | Andrographis paniculata | in vitro: 20 µM | Inhibiting proliferation and inducing apoptosis of SW620 cells. | TLR4/NF-κB/MMP-9 pathway. | [22] |
Resveratrol | Polygonum multiflorum | in vitro: 30, 40, 50 mM | Reducing LPS-induced inflammatory responses of Caco-2 and SW480 cell. | / | [23] |
Baicalein | Scutellaria baicalensis | in vitro: 7.5, 15 µM; 3.125, 6.25, 12.5, 25 µM; in vivo: 10, 20 mg/kg; | Inhibiting proliferation, migration and angiogenesis in CRC. | TLR4/HIF-1α/VEGF pathway. | [25] |
Baicalin | Scutellaria baicalensis | in vitro: 5–80 μg/mL; 0, 5, 10, 20 μM; in vivo: 20, 40 mg/kg; | Triggering apoptosis and anti-tumor immunity, and inhibiting migration in CRC. | TLR4/NF-κB pathway. | [26] |
Berberine | Coptis chinensis | in vivo: 50, 100 mg/kg | Regulating short-chain fatty acid metabolism and alleviating the CAC. | TLR4/p-NF-κB p65/IL-6/p-STAT3 pathway. | [24] |
Casticin | Vitex trifolia | in vitro: 10–100 μM; 40 μM | Inducing G2/M-phase arrest and apoptotic, increasing ROS production and decreasing mitochondria membrane potential and Ca2+ of colo 205 cells. | / | [134] |
Decursin | Angelica sinensis | in vitro: 10 μM | Inhibiting inflammation and metastasis in CRC. | / | [27] |
Ganoderic acid | Ganoderma lucidum | in vivo: 50 mg/kg | Alleviating chemotherapy-induced fatigue in CRC. | TLR4/Myd88/NF-κB pathway. | [135] |
Glycyrrhizin | Glycyrrhiza uralensis | in vivo: 15 mg/kg | Inhibiting the inflammation in CRC. | HMGB1/TLR4/NF-κB pathway. | [73] |
Quercetin | Ginkgo biloba | in vitro: 300, 600 µM | Decreasing chemoresistance in CRC. | TLR4/NLRP3 and ERK/NLRP3 pathway. | [110] |
Evodiamine | Evodia rutaecarpa | in vitro: 100, 200 µM; in vivo: 10 mg/kg | Inhibiting inflammation in CRC; Inducing G2/M-phase arrest of SW480 cells. | / | [136] |
Corylin | Psoralea corylifolia | in vivo: 25, 100 mg/kg | Inhibiting inflammation, proliferation of CSCs and colon epithelial cell, improving microbial diversity and community richness, regulating macrophage polarization in CRC. | TLR4/p38/AP-1 pathway. | [137] |
Rosmarinic acid | Perilla frutescens | in vitro: 25, 50 μM; in vivo: 30 mg/kg | Inhibiting inflammation of CRC. | TLR4/NF-κB/STAT3 pathway. | [100] |
Dihydroartemisinin | Artemisia annua | in vitro: 1–40 μM; in vivo: 10 mg/kg | Inhibiting inflammation of CRC; Improving cell cycle inhibition and apoptosis in CRC cells. | TLR4 signaling pathway. | [138] |
4.2. Formulas of TCMs with Anti-CRC Effects through TLR4 Signaling Pathway
4.3. The Synergistic Effects of TCM Production with Conventional CRC Therapies
4.3.1. Enhanced Efficacy
4.3.2. Reduced Side Effects
4.3.3. Inhibition of Chemoresistance
4.3.4. Reducing Toxicity
4.4. The Safety/Toxicity of These TCM Compounds
Natural Compounds | Toxicity or Side Effects | Potential Side Effects in VigiBase | Ref. |
---|---|---|---|
Andrographolide | Reproductive toxicity, nephrotoxicity, taste disturbance, headache, fatigue, and diarrhea, anaphylactic reaction | Gastrointestinal disorders, general disorders and administration site conditions | [184] |
Resveratrol | Reproductive toxicity, cardiac toxicity, nephrotoxicity, increased hepatotoxicity, risk of bleeding and anaphylactic reaction | Eye disorders, gastrointestinal disorders, metabolism and nutrition disorders, etc. | [185] |
Baicalein | Elevated levels of C-reactive protein and triglycerides, elevated levels of alanine aminotransferase and aspartate aminotransferase, proteinuria and abdominal pain, constipation | / | [186] |
Baicalin | / | / | / |
Berberine | Diarrhea and constipation, exacerbation of jaundice in neonates with glucose-6-phosphate dehydrogenase deficiency and uterine stimulation | Blood and lymphatic system disorder, ear and labyrinth disorders and eye disorders, etc. | [187] |
Casticin | / | / | / |
Decursin | / | / | / |
Ganoderic acid | / | / | / |
Glycyrrhizin | / | Blood and lymphatic system disorders, cardiac disorders and ear and labyrinth disorders, etc. | / |
Quercetin | / | Blood and lymphatic system disorders, cardiac disorders and ear and labyrinth disorders, etc. | / |
Evodiamine | / | / | / |
Corylin | / | / | / |
Rosmarinic acid | / | / | / |
Dihydroartemisinin | Impairment of oocyte maturation | Ear and labyrinth disorders, eye disorders and gastrointestinal disorders, etc. | [189] |
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ACAT1 | Acyl coenzyme A cholesterol acyltransferase 1 |
ADAM | A disintegrin and metalloproteinase |
AKT | Protein kinase B |
AOM | Azoxymethane |
CAC | Colitis-associated colon cancer |
COX | Cyclooxygenase |
CRC | Colorectal cancer |
CSCs | Cancer stem cells |
CXCR7 | CXC chemokine receptor 7 |
DAMPs | Damage-associated molecular patterns |
DCs | Dendritic cells |
DSS | Dextran sodium sulfate |
EGFR | Epidermal growth factor receptor |
EMT | Epithelial–mesenchymal transition |
ERK | Extracellular regulated protein kinases |
Gal-1 | Galectin-1 |
GSK-3β | Glycogen synthase kinase-3β |
HMGB1 | High-mobility group box 1 |
HSP110 | Heat shock protein-110 |
IBD | Inflammatory bowel disease |
IECs | Intestinal epithelial cells |
IL | Interleukin |
IRAKs | IL-1 receptor-associated kinases |
IRF | Interferon Regulatory Factor |
JNK | c-Jun N-terminal |
LPS | Lipopolysaccharide |
MANs | Monophosphoryl lipid A- assembled nanovaccines |
MAPK | Mitogen-associated protein kinase |
MD2 | Myeloid differentiation protein-2 |
MDSCs | Myeloid-derived suppressor cells |
MIF | Macrophage inhibitory factor |
MyD88 | Myeloid differentiation primary response gene 88 |
NF-κB | Nuclear factor kappa-B |
NK | Natural killer |
PAR2 | Protease-activated receptor 2 |
PGE-2 | Prostaglandin E2 |
PI3K | Phosphatidylinositol-4,5-bisphosphate 3-kinase |
ROS | Reactive oxygen species |
STAT3 | Signal transducers and activators of transcription 3 |
TAMs | Tumor-associated macrophages |
TAK1 | Transforming growth factor-βactivated protein kinase 1 |
TAp63 | Transcriptionally active p63 |
TCMs | Traditional Chinese medicines |
THBS2 | Thrombospondin 2 |
TILs | Tumor-infiltrating lymphocytes |
TIPE2 | The tumor necrosis factor (TNF)-α-induced protein 8-like-2 |
TLR | Toll-like receptor |
TNF | Tumor necrosis factor |
TOPORS | TOP1-binding arginine/serine-rich protein |
TRAF6 | Tumor necrosis factor receptor-associated factor 6 |
TRAM | TRIF-related adaptor molecule |
TIRAP | Toll/interleukin-1-receptor-domain-containing adaptor protein |
TRIF | Toll/interleukin-1-receptordomain-containing adaptor inducing interferon-β |
VEGF | Vascular endothelial growth factor |
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Full Official Name | Concentration/Dosage | Major Effects | Involved Pathways | Ref. |
---|---|---|---|---|
Asparagus polysaccharide | in vitro: 0.25, 0.5 mg/mL | Inhibiting MDSC activity in CRC. | / | [46] |
Arctiumlappa root | in vitro: 4 mg/mL | Increasing apoptosis in CRC; Decreasing cancer cell attachment to the surface of CRC. | TLR-4/AKT/ERK pathway. | [133] |
Atractylodes macrocephala polysaccharides | in vitro: 50, 100, 200, 400 μg/mL | Enhancing the phagocytosis of BMDMs by CRC cells. | TLR4/MyD88 pathway. | [141] |
Curcumae longae Rhizoma | in vivo: 500 mg/kg | Reversing the 5-Fluoruracil resistance in SW480 cells. | TLR4/PI3K/Akt/mTOR pathway. | [106] |
Ganoderma lucidum polysaccharide | in vivo: 200, 300 mg/kg | Inhibiting inflammation and tumorigenesis in colon. | TLR4/MyD88/NF-κB pathway. | [142] |
Lentinus edodes Polysaccharides | in vitro: 30 µg/mL; 0.5, 1, 2 mg/mL in vivo: 30 mg/kg; 5, 10, 20 mg/kg | Inhibiting lymphangiogenesis and metastasis of lymphatic, and inflammation in CRC. | TLR4/JNK and TLR4/NF-κB pathway. | [143,144] |
Shubu Wenshen Guchang recipe | in vivo: 100, 200 mg/kg | Inhibiting intestinal damage in CRC. | TLR4/NF-κB pathway. | [145] |
Yiyi Fuzi Baijiang powder | / | Inhibiting inflammation in CRC. | TLR4/NF-κB pathway. | [146] |
Sanwu Baisan Decoction | in vitro: 5.647 mg/mL in vivo: 5, 10, 50 mg/kg | Remodeling gut microbiota and inducing apoptosis in CRC. | TLR-4/COX-2/PGE-2 pathway. | [48] |
Xiaochai Hu Decoction | in vivo: 10.27, 20.54 mg/kg | Reducing depressive symptoms and reversing gut dysbiosis in CRC | TLR4/MyD88/NF-κB pathway. | [147] |
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Luo, Y.; Zhang, G.; Hu, C.; Huang, L.; Wang, D.; Chen, Z.; Wang, Y. The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment. Molecules 2024, 29, 2727. https://doi.org/10.3390/molecules29122727
Luo Y, Zhang G, Hu C, Huang L, Wang D, Chen Z, Wang Y. The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment. Molecules. 2024; 29(12):2727. https://doi.org/10.3390/molecules29122727
Chicago/Turabian StyleLuo, Yan, Guochen Zhang, Chao Hu, Lijun Huang, Dong Wang, Zhejie Chen, and Yumei Wang. 2024. "The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment" Molecules 29, no. 12: 2727. https://doi.org/10.3390/molecules29122727
APA StyleLuo, Y., Zhang, G., Hu, C., Huang, L., Wang, D., Chen, Z., & Wang, Y. (2024). The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment. Molecules, 29(12), 2727. https://doi.org/10.3390/molecules29122727