Table 1.
Therapeutic applications of antioxidant supplementation for H. pylori-induced gastric cancer.
| No. | Antioxidant Supplementation | Model | Inference | References |
|---|---|---|---|---|
| 1 | Scutellarin (20 and 80 μmol/L) | AGS, HGC-27, and GES-1 cell lines | SCU suppressed gastric cancer cell proliferation and increased apoptosis by inhibiting the Wnt/β-catenin pathway. | [146] |
| 2 | ASX (1 or 5 µM) for 3 h | H. pylori-infected AGS cells | ASX inhibited H. pylori-induced integrin α5-mediated cell adhesion and migration by decreasing ROS levels and suppressing JAK1/STAT3 activation. | [94] |
| 3 | Geraniol (30–100 μM) | H. pylori-infected GES-1 cells | Increased the expression of peroxiredoxin-1 (Prdx-1) in GES-1 cells. | [147] |
| 4 | Carvacrol (10, 25, 50, and 100 mg/kg BW) | MNNG-induced GC (200 mg/kg BW)/60 days/Wistar albino rats | High doses of carvacrol (50 and 100 mg/kg BW) increased oxidative stress, inflammation, and apoptosis. | [148] |
| 5 | SCU (10, 20, and 30 mg/kg) | MNNG-induced gastric carcinogenesis/AGS cell line and Wistar albino rats | A reduction in LDH activity, ulcer index, pH, mucus weight, and percentage inhibition of ulcers was observed after SC treatment. | [149] |
| 6 | Korean red ginseng extract (RGE) (0.01–1μg/mL) for 1 h | H. pylori-infected AGS cells | RGE treatment decreased IL-8 production, mitochondrial dysfunction, and ROS production by activating Nrf2, inducing SOD-1 and HO-1, and decreasing ROS levels. | [115] |
| 7 | ASX (1 or 10 µM) for 3 h | H. pylori-infected AGS cells | ASX suppressed MMP expression, cell invasion, and migration via inhibition of PI3K/AKT/mTOR/NF-κB signaling. | [60] |
| 8 | Curcumin (5 mM and 20 mM) | H. pylori-infected AGS cells | Curcumin treatment inhibited the vacuolation activity of H. pylori. | [150] |
| 9 | Phycocyanin (150 µM) | H. pylori-infected AGS cells | Phycocyanin inhibited AGS cell hyperproliferation by regulating ROS/MAPK signaling pathways and reducing c-myc and CyclinD1 expression. | [112] |
| 10 | SCU (0–80 µM) | MGC-803 and AGS | SCU inhibited GC growth and EMT by regulating the PTEN/PI3K pathway. | [151] |
| 11 | Silibinin (20 mg/kg or 200 mg/kg) for 4 or 8 weeks |
H. pylori-infected C57BL/6 mice/ MKN-1 cell line |
Silibinin suppressed H. pylori infection by inhibiting COX2 and inducing iNOS expression by suppressing NF-κB and STAT pathways. | [152] |
| 12 | β-carotene (0.1 or 0.2 µM) for 2 h | H. pylori-infected AGS cells | β-carotene suppressed MAPK-driven MMP-10 expression and cell invasion by promoting PPAR-γ-mediated catalase expression and inhibiting ROS levels. | [110] |
| 13 | Vicenin-2 (40 µM) | H. pylori-infected GES cells | Vicenin-2 enhanced Nrf2 and PTEN in GES cells. | [153] |
| 14 | Luteolin (30 µM) | H. pylori-infected CRL-1739 cells | Luteolin significantly induced IL-8, IL-10, and NF-κB expression and reduced ADAM-17 expression. | [154] |
| 15 | Astragalin (0–40 µM)—6 h | HGC-27, MGC-803, and MKN-28 cell lines |
Astragalin-induced apoptosis inhibited the migration and invasion via inhibition of the PI3K/AKT signaling pathway. | [155] |
| 16 | Eugenol (0–240 ug/mL) | AGS cell lines | Eugenol inhibited the TGF-β/SMAD4 signaling pathway in GC. | [156] |
| 17 | Celastrol (5 mM for 1 h) | SGC-7901 and BGC-823 cell lines | Increased cellular ROS levels led to ROS-dependent endoplasmic reticulum stress, mitochondrial dysfunction, and apoptosis. | [157] |
| 18 | Tanshinone IIA (2 and 4 4 μM) | BGC-823 and NCI-H87 | Tan IIA upregulated p53 expression and lipid peroxidation (LPO); ferroptosis downregulated xCT expression, intracellular glutathione (GSH), and cysteine levels.. | [158] |
| 19 | Nobiletin | H. pylori-infected GES-1 cells. | Nobiletin significantly decreased the expression of TNF-α, IL-6, COX-2, PI3K, AKT, and MAPK molecules, including p38 and c-Jun amino-terminal expression in H. pylori-infected GES-1 cells. | [159] |
| 20 | Zeaxanthin (100 μM for 24 h) | AGS, KATO-3, MKN-28, MKN-45, NCI-N87, YCC-1, YCC-6, YCC-16, SUN-5, SUN-216, SUN-484, and SUN-668 cell lines | Zeaxanthin against GC by inhibiting the ROS-mediated MAPK, AKT, NF-κB, and STAT3 signaling pathways. | [160] |
| 21 | Celastrol | MKN45 cells | Celastrol inhibited proliferation, migration, and invasion and inactivated PTEN/PI3K/AKT and NF- κB signaling pathways in MKN45 cells by downregulating miR-21. | [161] |
| 22 | Celastrol (0 or 2 μM) | HGC27 and AGS cells | Celastrol activated RIP1/RIP3/MLKL pathways and suppressed the level of pro-inflammatory cytokines by downregulating biglycan (BGN) in HGC-27 and AGS cells. | [162] |
| 23 | ASX (1 or 5 μM) for 3 h | H. pylori-infected AGS cells | ASX inhibited the reduction in mitochondrial ROS caused by H. pylori and decreased SOD2 and SOD activity. | [163] |
| 24 | ASX (1 or 5 μM) for 3 h | H. pylori-infected AGS cells | Astaxanthin inhibited H. pylori-induced mitochondrial dysfunction and ROS-mediated IL-8 expression by activating PPAR-γ and catalase. | [111] |
| 25 | Ebselen (0 or 100 μM) | AGS and MGC-803 cells | Ebselen may inhibit ROS production triggered by H. pylori LPS treatment via GPX2/4 instead of TLR4 signaling and reduce phosphorylation of p38 MAPK, resulting in altered production of IL-8. | [164] |
| 26 | α-lipoic acid (10 and 20 µM for 2 h) | H. pylori-treated AGS cells | α-lipoic acid inhibited ROS levels, IL-8 expression, activation of MAPK, ERK1/2, JNK1/2, p38, JAK1/2, STAT3, and NF-κB signaling pathways. | [59] |
| 27 | Epigallocatechin Gallate (EGCG) (0.05% EGCG in drinking water) | H. pylori-infected Mongolian gerbils | EGCG inhibited the IL-1β, TNF-α, COX-2, and iNOS in the gerbil model of H. pylori-induced inflammation. |
[165] |
| 28 | Artemisia and/or green tea extracts | H. pylori-infected and high-salt-diet-administered C57BL/6 mice | Artemisia and/or green tea extract treatment significantly decreased the expressions of COX-2, TNF-α, IL-6, lipid peroxide, and activated STAT3 relevant to H. pylori infection. | [166] |
| 29 | Curcumin | H. pylori-infected 8-week-old BALB/c mice | Curcumin reduced the LPO, MPO level, urease activity, the number of colonized bacteria, levels of anti-H. pylori antibodies, biofilm formation, IFN-γ, IL-4, gastrin and somatostatin levels in serum, and minimum inhibitory concentration. | [167] |
| 30 | Nobiletin (0–50 µM) | SNU-16 cells | Nobiletin-induced apoptosis in SNU-16 cells was mediated via intracellular ER stress-mediated protective autophagy. | [168] |
| 31 | Eugenol (0.1–1.7 mM) | AGS cells | Eugenol induced apoptosis (caspase 3 and caspase 8) in the presence of as well as in the absence of functional p53. | [169] |
| 32 | α-LA (10 μM and 20 μM) 2 h | H. pylori-infected AGS cells | α-LA inhibited NADPH oxidase and ROS production, inhibition of NF-κB and AP-1 activation, induction of oncogenes, β-catenin nuclear translocation, and hyperproliferation in AGS cells. | [170] |
| 33 | Celastrol | AGS and YCC-2 cells GC xenografted mice |
Celastrol induced apoptosis and autophagy in gastric cancer cells. | [171] |
| 34 | RGE (at various concentrations) | H. pylori-infected AGS cells | RGE inhibited the expression of MCP-1 and iNOS by suppressing the activation of NADPH oxidase and Jak2/Stat3 signaling. | [93] |
| 35 | Catechins (CAs), sialic acid (SA) combination of CA and SA (CASA) | H. pylori-infected AGS cells and BALB/c mice | CASA attenuated the caspase-1-mediated epithelial damage. | [172] |
| 36 | Celastrol (0–5 µM) | BGC-823, MGC-803, and SGC-7901 cells | Celastrol induced apoptosis by inhibiting NF-κB activity by upregulating miR-146a expression. | [173] |
| 37 | Diphenyleneiodonium (DPI) (2.5 or 5.0 μM) 2 h | H. pylori-infected AGS cells | DPI inhibited H. pylori-induced activation of MAPKs and MCP-1 expression in AGS cells. | [106] |
| 38 | Sporoderm-removed spores of G. lucidum (RSGLP) | H. pylori-infected AGS cells | RSGLP is more effective at inhibiting gastric cancer cell viability and may serve as a promising autophagy inhibitor for gastric cancer. | [174] |
| 39 | Resveratrol (100 mg/kg body weight/day) orally for six weeks | Male Kunming mice | Resveratrol inhibited oxidative stress and inflammation in H. pylori-infected mucosa via the suppression of IL-8, iNOS, and NF-κB and the activation of the Nrf2/HO-1 pathway. | [175] |