Table 3.
Natural products targeting TAMs for colon treatment and the mechanism of action.
| Categories | Compound | Sources | Pharmacological function | In vivo model and administration dose | In vitro model | Molecular mechanisms | Effect on the macrophages | Anti-tumor function | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| Polyphenols | Procyanidins | Litchi | anti-inflammation, anticancer, antioxidation | female BALB/c mice: CT26 tail vein injection | / | ↓ CD68, ARG1, CD206, CCL2 | decrease TAMs infiltration | suppress tumor growth and lung metastasis, activate T cell immunity, alleviate macrophages induced inflammation | (166) |
| Curcumin | Curcumae longae Rhizoma | anticancer, antioxidation, immune modulation | / | THP-1 SW620, HCT116 |
↓ IL-10, ARG1, CD163, MACC1 | inhibit M2 polarization | suppress tumor cell proliferation and migration | (167) | |
| Piceatannol | seeds of Euphorbia lagascae | anti-inflammation, anticancer, antioxidation | male BALB/c athymic nude mice: SW480 and M2-like macrophages subcutaneous injection, 10, 50 mg/kg | THP-1 SW480 |
↓ CD163, TGF-β1, ARG1, Fibronectin | inhibit M2 polarization | suppress tumor growth and EMT | (168) | |
| Luteolin | ResedaodorataL. | anti-inflammation, anticancer, antioxidation | / | THP-1 SW480, SW620 |
↓ IL-6, p-STAT3 | inhibit M1 polarization | suppress tumor cell proliferation and invasion | (169) | |
| Cannabidiol | Cannabis | neuroprotective, anti-inflammation, anticancer, anti-emetic | C57BL/6J: MC38 subcutaneous injection, 10 mg/kg | BMDM MC38 |
↓ CD206, ↑ CD86, iNOS, ↓ ATP, MDA, OXPHOS, β-oxidation, p-P13K, p-AKT, ↑ glycolysis | promote M1 polarization, inhibit M2 polarization | suppress tumor growth, modulate the suppressive TME, reduce Tregs and enhance CD8+ T and NK cell infiltration | (170) | |
| Polyphenols-rich components from seaweeds | Seaweeds,Gracilaria | anti-inflammation, anticancer | / | RAW264.7 CCD-18Co, HCT116 |
↓ NO, IL-1, IL-6, TNF-α, iNOS, COX2, ↑ HO-1 | regulate TAMs pro-inflammatory activity | suppress tumor cell proliferation, promote apoptosis and cell cycle arrest | (171) | |
| Non-extractable phenolics from strawberry | Strawberry | anti-inflammation, anticancer, anti-diabetes | / | RAW264.7 HCT116 |
↓ iNOS, c-FOS, ↑ HO-1 | reduce TAMs inflammation | suppress tumor cell proliferation, migration, induce cell cycle arrest in G2/M phase, promote apoptosis | (172) | |
| Hydroxygenkwanin | Dracocephalum moldavica L. | anticancer, anti-inflammation, antioxidation | C57BL/6J: MC38 intraperitoneally injection, 0.1, 0.25, 0.5 mg/kg | BMDM MC38 |
↑ TNF-α, iNOS, IL-6, IL-1β, p-STAT5, p-NF-κB, ↓ARG1, CD206, Ym1, JMJD3, p-STAT6, PPAR-γ | promote M1 polarization, inhibit M2 polarization | suppress tumor growth and peritoneal metastasis through the modulation of macrophages | (173) | |
| Tetrahydrocurcumin | Curcuma longa L. | anticancer, anti-inflammation, antioxidative | AOM/DSS mice: 50, 100, 200 mg/kg | THP-1 HCT116, MC38 |
↓ CD206, ARG1, IL-10, SPP1, ↑ iNOS, IL-1β, TNF-α | inhibit M2 polarization | suppress tumorgenesis and progression via modulating the SPP1/CD44 axis and activating ERK signaling pathway | (174) | |
| Polysaccharides | Fucoidan | Brown algae | anticancer, immune modulation, antioxidation | male BALB/C mice: HCT116 subcutaneous injection, 200, 500 mg/kg | RAW264.7 HCT116, RKO |
↑ CD86, ↓ CD206, ↑ TLR4, p-P13K, p-AKT, p-mTOR, C/EBPα, glycolysis, ↓PPAR-γ | promote M1 polarization | inhibit tumor growth, promote tumor cell apoptosis | (175) |
| Polysaccharides from Nostoc commune | Nostoc commune Vaucher | antioxidation, anti-inflammation, anti- carcinogenesis |
BALB/c mice: CT26 xenograft, 200 mg/kg | BMDM SW480, SW620, DLD-1, CT26, HT-29, HCT116 |
↑ TNF-α, IL-1β, IL-6, IL-12β, p-AKT, p-JNK1/2, ↓ IKB-α | promote M1 polarization | inhibit tumor growth, promote tumor cell apoptosis | (176) | |
| Safflower polysaccharide | Safflower petals | anti-inflammation, anticancer, immune modulation | AOM/DSS mice: 50 mg/kg | RAW264.7 HCT116, SW480, LoVo, RKO, MC38 |
↑ iNOS, IL-23, CD16, CD80, p-p65, p-IKBα, TNF-α, IL-6, NO | promote M1 polarization | suppress tumor growth and induce tumor cell apoptosis via regulating macrophage polarization | (177) | |
| Cnidium officinale polysaccharide | Cnidium officinale | anti-inflammation, anti-anemia | / | RAW264.7 HCT116 |
↑NO, TNF-α, IL-1β, IL-6, IL-10, p-p65, p-p38, p-JNK, p-ERK1/2 | enhance pro-inflammatory activity of macrophages | promote tumor immune response | (178) | |
| Beta-1,6 glucan | Armillaria mellea | anti-inflammation, anticancer, immune modulation, antioxidation | female BALB/c mice: CT26 subcutaneous injection, 10, 20 mg/kg | RAW264.7 CT26, DLD-1, HCT116 |
↑ NO, TNF-α, IL-6,iNOS, ↓ IL-10, CD206, Ym1, ARG1, IKBα, ↑ p-p65, p-ERK, p-JNK | promote the polarization of M2 to M1 | suppress tumor growth, promote tumor cell apoptosis | (179) | |
| Ganoderma lucidum polysaccharide | Ganoderma lucidum | anti-inflammation, anticancer, immune modulation | APCmin/+ mice: 750 mg/kg | / | ↓ IL-1β, IFN-γ, FOXP3, TNF-α, ↑ IL-4, IL-10, IL-12, IL-13 | promote the polarization of M1 to M2 | reduce polyps, prevent colon tumorigenesis, regulate gut microbiota | (180) | |
| Polysaccharides from ginseng leaves | Ginseng leaves | anticancer, immune modulation | BALB/c mice: colon 26-M3.1 tail vein injection, 4-500 μg/mice | peritoneal exudate macrophages Colon 26-M3.1 |
↑ TNF-α, IL-12 | activate macrophage | suppress tumor growth and metastasis | (181) | |
| Saponins | panaxynol | American ginseng | anti-inflammation, immune modulation, antioxidation | AOM/DSS mice: 2.5 mg/kg | BMDM | ↓ IL-6, IL-13, TGF-β1 | decrease M2 infiltration | suppress tumor growth, promote tumor cell apoptosis | (182) |
| Ginsenoside-Rp1 | Panax ginseng | anti-inflammation, immune modulation, antioxidation | / | J774A.1 CT26 |
↓ NO, IL-1β | inhibit TAMSs activation | suppress tumor cell proliferation | (183) | |
| Astragaloside IV | Astragalus membranaceus | anti-inflammation, antioxidation, lowering blood pressure | female BALB/C mice: CT26 subcutaneous injection, 15 mg/kg | BMDM CT26 |
↓ ARG1,Mrc1, TGF-β, IL-10, VEGF-α, ↑ IL-12, Nos2, IFN-γ, TNF-α | promote the polarization of M2 to M1 | suppress tumor growth and activate immune response | (184) | |
| Gypenoside | Gynostemma pentaphyllum | anti-inflammation, antioxidation, metabolic Regulation | APCmin/+ mice: 300 mg/kg | / | ↓ iNOS↓, CXCL10, ↑ Ym-1, CD206, Trem2, ARG1 | promote the polarization of M1 to M2 | reduce polyps, prevent colon tumorigenesis | (180) | |
| Terpenoids | Diterpene ent-polyalthic acid | Copaifera reticulata Ducke oleoresin | analgesic, antioxidation, anticancer | male Wistar rats: 1,2-dimethylhydrazine intraperitoneal injection, 80 mg/kg | peritoneal macrophages | ↓ NO, PGE2 | inhibit TAMs infiltration | suppress colon carcinogenesis and DNA damage | (185) |
| dihydroisotanshinone I | Salvia miltiorrhiza Bunge | anticancer, cardioprotective effects | BALB/c-nu nude mice: HCT116 xenograft, 30 mg/kg | RAW264.7 HCT116, HT-29 |
CCL2↓ | suppress TAMs activation | suppress tumor cell recruitment ability of macrophage, promote tumor cell apoptosis | (186) | |
| Triptolide | Tripterygium wilfordii Hook. F | anti-inflammation, antimicrobial, antifibrosis, anticancer | BALB/c mice: CT26 subcutaneous injection, 0.1, 0.2, 0.4 mg/kg | RAW264.7 HT29, CT116 |
↓ ARG1, CD206, IL-10, CXCL12 | decrease TAMs infiltration, inhibit M2 polarization | suppress tumor growth and remodel TME through NF‐κB p65 and ERK1/2 axis |
(187) | |
| Oridonin | Rabdosia rubescens | anticancer, anti-angiogenesis | male BALB/c nude mice: HCT116 subcutaneous injection, 40 mg/kg | / | ↓ CD206 | decrease M2 infiltration | suppress tumor growth and angiogenesis through JAK2/STAT3 signaling pathway | (188) | |
| Cucurbitacin B | Muskmelon pedicel | anticancer, anti-inflammation, antioxidation | C57BL/6 mice: CT26 subcutaneous injection, 0.5, 1 mg/kg | RAW264.7, THP-1 HCT116, CT26 |
↓ Ym1, Fizz1, ARG1, CCR2, p-JAK, p-STAT3 | inhibit M2 polarization | suppress tumor growth, inhibit tumor cell invasion and migration, regulate TME | (H. 189) | |
| Oleuropein | Olea europaea L. leaves | anti-inflammation, immune modulation, antioxidation | PIRC rats: 100 mg/kg | RAW264.7 HCT116 |
↓ iNOS, IL-1β, IL-6, TGF-β, COX2 | suppress TAMs activation | suppress tumorgenesis, promote tumor cell apoptosis | (190) | |
| Quinones | Emodin | Rheum palmatum, Polygonum cuspidatum, and polygonum multiflorum | anti-inflammation, anticancer | APCmin/+ and AOM/DSS mice: 40, 80 mg/kg | BMDM C26 |
↓ P2X7, p-STAT3 | decrease M2 proliferation | reduce polyp and tumorgenesis, regulate TME | (191) |
| Bullatacin | Annonaceae | anticancer | / | SW480, HT-29 | ↑ CRT, HSP90, HMGB1 | promote macrophage phagocytosis | promote immunogenic tumor cell death by activating endoplasmic reticulum stress | (192) |