Table 1.
The possible anti-AFs mechanism of action of PPs.
| Class | Compound | AFs | Mechanism of action | References |
|---|---|---|---|---|
| Flavonols | Quercetin | AFB1 | • Improving antioxidant defense | (191, 327–336) |
| • Inhibiting lipid peroxidation | ||||
| • Improving the enzymatic activity of SOD, GSH, and CAT. | ||||
| • Protecting brain cells from AFs-related oxidative damage and decreasing hepatocellular damage | ||||
| • Decreasing the expression of Bax and caspase 3 genes | ||||
| • Regulation of cellular apoptosis. | ||||
| • Inhibiting cytochrome P450 reductase | ||||
| • Protecting liver cells from oxidative stress damage caused by AFB1 | ||||
| • Decreasing the binding affinity of AFB1 to HSA | ||||
| • Activating the Nrf2-ARE signaling pathway | ||||
| • Increasing hepatoprotective effect after combination with nanoparticles | ||||
| • Decreasing DNA damage | ||||
| • Inhibiting AFB1 binding to cellular DNA | ||||
| • Preventing the biosynthesis of AFB1 by-product derivatives | ||||
| • Decreasing the elevated activity of PKC | ||||
| • Inhibiting the formation of AFB1-DNA adducts | ||||
| AFM1 | • Inhibiting the bio-transformation of AFB1 | (464) | ||
| • Decreasing the synthesis of AFM1 by regulation of related signaling pathways. | ||||
| • Regulating the activity of GSH/GST enzymatic function | ||||
| • Inhibiting the pro-oxidant activity of AFB1 | ||||
| Rutin | AFB1 | • Preventing DNA damage by regulation of DNA-associated enzymes | (465, 466) | |
| • Displaying antimutagenic activity | ||||
| Azaleatin | AFs | Not reported | – | |
| Fisetin | AFB1 | • Modulating antioxidant enzymes | (332, 335, 410, 413, 467–469) | |
| • Modulating the expression of inflammatory factors | ||||
| • Decreasing aflatoxin-related oxidative stress | ||||
| • Regulating the expression of TNFα and IL1α proinflammatory cytokines | ||||
| • Modulating the enzymatic activity of GST | ||||
| • Inhibiting hepatocarcinogenesis by regulating inflammatory-based signaling pathways | ||||
| • Inhibiting cytochrome c P450 reductase | ||||
| • Preventing metabolic activation of AFB1 by-products | ||||
| • Inhibiting the formation of AFB1-DNA complexes | ||||
| • Modulating the enzymatic activity of protein kinases such as GSK3β, PDK, PKB, PI3K | ||||
| • Suppressing Akt protein signaling pathway | ||||
| • Displaying dose-dependent antimutagenic effects against mutagenicity of AFB1 | ||||
| Galangin | AFB1 | • Inhibiting cytochrome c P450 reductase | (332, 470, 471) | |
| • Preventing AFB1 conversion to toxic metabolites | ||||
| • Protecting DNA from damage | ||||
| • Preventing metabolic transformation of AFs | ||||
| • Improving the activity of detoxifying enzymes | ||||
| • Reducing the hepatotoxicity of AFs | ||||
| Gossypetin | AFs | Not reported | – | |
| Kaempferol | AFB1 | • Inhibiting the chemical transformation of AFB1 | (409–414) | |
| • Displaying antimutagenic effects against toxic derivatives of AFB1 | ||||
| • Preventing lipid peroxidation | ||||
| • Attenuating liver cell apoptosis | ||||
| • Scavenging free toxic radicals in metabolic pathways of AFs metabolism | ||||
| • Improving body antioxidative system | ||||
| • Inhibiting AFB1 bioactivation in liver | ||||
| • Regulating cytochrome P450 activity | ||||
| • Suppressing the formation of AFB1-DNA adducts | ||||
| Myricetin | AFB1 | • Regulating cytochrome P450 activity | (332) | |
| Morin | AFB1 | • Improving kidney injuries | (332, 429, 472) | |
| • Regulating ALT and AST activity | ||||
| • Improving hepatocyte disruption | ||||
| • Attenuating inflammatory signaling pathways | ||||
| • Improving renal cells necrosis | ||||
| • Decreasing the level of MDA | ||||
| • Regulating the activity of SOD, GSH, and CAT enzymes | ||||
| • Decreasing the expression of TNFα, IL-6, IL-1β, iNOS, COX-2, caspase-1/3/11 | ||||
| • Inhibiting AFB1-induced heterophil extracellular traps release | ||||
| • Regulating oxidative and inflammatory responses | ||||
| • Improving complications of aflatoxicosis | ||||
| • Preventing biotransformation of AFB1 metabolic derivatives | ||||
| • Improving detoxification of AFs | ||||
| Rhamnetin | Preventing biotransformation of AFB1 metabolic derivatives | (471) | ||
| Natsudaidain | AFs | Not reported | – | |
| Kaempferide | AFs | Not reported | – | |
| Isorhamentin | AFB1 | • Protecting cells against oxidative stress | (327, 473) | |
| • Inhibiting AFB1 genotoxicity effects | ||||
| • Suppressing lipid peroxidation | ||||
| Rhamnazin | AFs | Not reported | – | |
| Astragalin | AFs | Not reported | – | |
| Robinin | AFs | Not reported | – | |
| Spiraeoside | AFs | Not reported | – | |
| Flavanones | Hesperetin | AFB1 | • Displaying antimutagenic effects against AFB1 metabolic derivatives | (410) |
| • Regulating cytochrome c P450 activity | ||||
| Hesperidin | AFB1 | • Inhibiting neural crest cells from apoptosis induced by AFB1 | (474) | |
| Naringenin | AFB1 | • Inhibiting bioactivation of AFB1 | (413, 475) | |
| • Regulating the activity of cytochrome P450 isoforms | ||||
| Naringin | AFB1 | • Inhibiting the induction of liver carcinoma | (476) | |
| Poncirin | AFB1 | • Attenuating cellular apoptosis | (411) | |
| • Displaying hepatoprotective effects | ||||
| • Inhibiting lipid peroxidation | ||||
| • Improving the activity of antioxidant enzymes | ||||
| • Protecting effects against oxidative stress | ||||
| Pinostrobin | AFs | Not reported | – | |
| Sterubin | AFs | Not reported | – | |
| Sakuranetin | AFs | Not reported | – | |
| Isoflavones | Genistein | AFB1 | • Mode of action similar to poncirin + antimutagenic effects | (411, 477) |
| Glycitein | AFs | Not reported | – | |
| Daidzein | AFs | Not reported | – | |
| Flavones | Apigenin | AFB1 | • Displaying antimutagenic effects by regulating SOS enzyme activity | (411, 478–480) |
| • Inhibiting metabolic activation of AFs | ||||
| • Suppressing oxidative stress and apoptosis | ||||
| • Showing hepatoprotective effects in combination with other PPs | ||||
| • Preventing ROS formation and DNA damage | ||||
| Luteolin | AFB1 | • Displaying antimutagenic effects in combination with other PPs | (478, 480–482) | |
| • Attenuating oxidative stress and apoptosis | ||||
| • Showing protective properties for liver cells | ||||
| • Activating the Nrf2 signaling pathway | ||||
| • Scavenging free toxic radicals | ||||
| • Decreasing the expression of Bax, caspase-3/9, Cytc genes | ||||
| • Increasing the expression of the Bcl-2 gene | ||||
| • Up-regulating HO-1, NQO1, GCLC, SOD1 | ||||
| • Improving liver injuries | ||||
| • Preventing ROS formation and DNA damage | ||||
| Tangeretin | AFB1 | • Displaying differential inhibitory effects on cytochrome c P450 activity | (332, 483, 484) | |
| • Minor regulating of mixed-function oxidase system | ||||
| • Inhibiting unscheduled DNA synthesis | ||||
| • Showing synergetic inhibitory effects in combination with other PPs. | ||||
| 6-Hydroxyflavone | AFs | Not reported | – | |
| Jaceosidin | AFB1 | • Displaying antimutagenic effects | (479) | |
| • Inhibiting metabolic activation of AFB1 metabolites | ||||
| Eupatilin | AFB1 | • Displaying a similar mode of action like Jaceosidin | (479) | |
| Chrysoeriol | • Displaying similar modes of action like Jaceosidin and eupatilin | (479) | ||
| Flavan-3-ols | Catechin | AFB1 | • Displaying antimutagenic effects against carcinogens in a dose-dependent manner | (485–489) |
| • Inhibiting CYP enzymatic activity | ||||
| • Regulation of NADPH-CYP reductase activity. | ||||
| • Forming chemical complexes with AFB1 | ||||
| • Preventing the formation of AFB1-DNA complexes | ||||
| • Improving liver injuries and oxidative stress complications | ||||
| Epicatechin | AFB1 | • Showing a similar mode of action to catechin. | (27, 443, 485, 488, 490) | |
| • Regulating of CYP enzymatic activity. | ||||
| • Displaying indirect protective effects against AFs-related oxidative stress. | ||||
| • Preventing mycotoxin-based DNA fragmentations. | ||||
| • Scavenging free toxic radicals | ||||
| • Protecting kidney cells from cell death | ||||
| • Displaying hepatoprotective effects | ||||
| • Inhibiting gastrointestinal absorption of AFB1 | ||||
| • Improving liver injuries caused by AFB1 | ||||
| Epigallocatechin | AFB1 | • Displaying a similar mode of action like tea PPs | (27, 485, 488) | |
| • Improving oxidative stress and liver injuries | ||||
| Epicatechin gallate | AFB1 | • Displaying a similar mode of action like tea PPs | (21, 27, 485, 488) | |
| • Alleviating oxidative stress and inflammation | ||||
| Epigallocatechin | AFB1 | • Attenuating oxidative stress | (21, 27, 488, 491) | |
| gallate | • Displaying antimutagenic effects in combination with other PPs | |||
| • Inhibiting the biosynthesis of AFB1 | ||||
| Epiafzelechin | AFs | Not reported | – | |
| Fisetinidol | AFs | Not reported | – | |
| Guibourtinidol | AFs | Not reported | – | |
| Mesquitol | AFs | Not reported | – | |
| Robinetinidol | AFs | Not reported | – | |
| Anthocyanins | Cyanidin | AFB1 | • Inhibiting the biotransformation of AFB1 in a dose-dependent manner | (194, 471, 492–494) |
| • Showing no inhibitory effects against the formation of AFB1-8,9-epoxide | ||||
| • Improving oxidative stress induced by AFs | ||||
| • Inhibiting the DNA and protein synthesis by AFs | ||||
| • Reducing DNA fragmentation induced by AFs | ||||
| • Inhibiting caspase-3 activation | ||||
| • Scavenging ROS produced by AFs metabolism | ||||
| • Showing hepatoprotective effects | ||||
| • Interfering with the interaction of AFB1 and HAS | ||||
| • Increasing cell viability HepG2 cells treated with AFB1 | ||||
| • Improving the activity of antioxidant enzymes GST, GPx and GR | ||||
| • Inhibiting DNA damage and oxidative stress induced by AFB1 | ||||
| • Showing antimutagenic potency against AFB1-induced liver damage in a dose-dependent manner | ||||
| • Improving antioxidant balance of cells in combination with glycosidic derivatives | ||||
| Delphinidin | AFB1 | • Inhibiting the biosynthesis of AFB1 in A. flavous | (495–497) | |
| • Showing indirect antimutagenic effects against mutagen metabolizing enzymes | ||||
| • Showing synergistic mode of action in combination with other anthocyanins | ||||
| • Suppressing the genotoxicity of AFs | ||||
| • Showing protective effects against colon carcinoma induced by AFs | ||||
| • Modulating phase II metabolism enzymes | ||||
| Europinidin | AFs | Not reported | – | |
| Pelargonidin | AFB1 | • Inhibiting biosynthesis of AFB1 in A. flavous | (495, 497, 498) | |
| • Displaying hepatoprotective effects | ||||
| • Activating phase II metabolism enzymes | ||||
| • Modulating Keap1/Nrf2 signaling pathway | ||||
| Malvidin | AFB1 | • Inhibiting biosynthesis of AFB1 in A. flavous | (495, 498, 499) | |
| • Displaying weak inhibitory effects on mycotoxins complications | ||||
| Peonidin | AFs | • Inhibiting the biosynthesis of AFB1 | (495, 499–501) | |
| • Strengthening plant defense system against AFB1 | ||||
| • Displaying weak inhibitory effects on mycotoxins complications | ||||
| • Partial inhibition of IL-8 secretion | ||||
| • Displaying anticancer activity but not related to induction of cancer by AFs/mycotoxins | ||||
| Rosinidin | AFs | Not reported | – | |
| Miscellaneous | Curcumin | AFB1 | • Improving oxidative liver damage | (417, 471, 502) |
| • Inhibiting lipid peroxidation | ||||
| • Regulating serum marker enzymes | ||||
| • Modulating the expression of inflammatory factors | ||||
| • Displaying hepatoprotective effects | ||||
| • Decreasing the complications of AFs-related inflammation | ||||
| • Regulating Nrf2/HO-1 signaling pathway | ||||
| • Influencing the autophagy of hepatocytes | ||||
| • Regulating the activity of GSH, SOD, CAT and GSH-Px enzymes | ||||
| • Inhibiting the biotransformation of AFB1 | ||||
| • Inhibiting the formation of AFB1-8,9-epoxide | ||||
| Coumarins | AFB1 | • Inhibiting the biotransformation of AFB1 in a dose-dependent manner | (471) | |
| Resveratrol | AFB1/2 | • Increasing N6-methyladenosine mRNA methylation | (177, 464, 503–511) | |
| • Displaying hepatoprotective effects by scavenging ROS molecules produced by AFB1 metabolism | ||||
| • Inhibiting AFB1-induced apoptosis | ||||
| • Regulating Nrf2/Keap1 signaling pathway | ||||
| • Inhibiting lipid peroxidation and regulating CYP genes (e.g., CYP1A1, CYP1A2) expression | ||||
| • Regulating ALT, AST, MDA, and GSH levels | ||||
| • Displaying hepatoprotective effects against liver injuries induced by AFs | ||||
| • Displaying antigenotoxic effects by preventing DNA damage and degradation | ||||
| • Competing with AFB1 to interact with DNA scaffold | ||||
| • Preventing chromone aberration | ||||
| • Decreasing the oxidative stress induced by AFB2 | ||||
| • Decreasing blood urea nitrogen | ||||
| • Improving phase II metabolisms enzymatic activity and modulating antioxidant enzymes, SIRT1 and NF-κB/NLRP3 signaling pathways | ||||
| • Inhibiting biosynthesis of AFB1 in A. flavous | ||||
| • Competing with AFB1 to bind to HSA subdomains | ||||
| • Inhibiting reproductive toxicity of mycotoxins | ||||
| Olive PPs | AFs | • Inhibiting biosynthesis of AFB1 in A. flavous | (512) |