Polyphenol-associated oxidative stress and inflammation in a model of LPS-induced inflammation in glial cells: do we know enough for responsible compounding?

Interaction of Polyphenols as Antioxidant and Anti-Inflammatory Compounds in Brain–Liver–Gut Axis

“…For instance, rat astrocytes treated with anthocyanin-rich lingonberry extract lowered ROS production, suggesting an anti-oxidative mechanism [24]. In a human astrocyte study, the secretion of IL-6 was reduced at low doses of LPS and anthocyanins [16]. However, in the absence of LPS, IL-6 secretion increased when treated with high concentration of anthocyanin, suggesting antioxidant toxicity with a single compound supplementation [16].…”

“…Human neuroblastoma SH-SY5Y cells (oxysterol induced) Quercetin ↓ TLR4 signaling [14] Human PBMC (oxLDL-induced) Quercetin ↓ TLR2 and TLR4 expressions, NF-κB activation, inflammatory enzymes activity [15] Human astrocytes (LPS-induced) Anthocyanins ↓ IL-6 secretion (low LPS and anthocyanin dose); ↑ IL-6 secretion (high anthocyanin dose in LPS absence) [16] Mouse BV2 microglial cells (LPS-induced) Blueberry extract ↓ NO and TNF-α release, iNOS and COX-2 expressions, NF-κB nuclear translocation [17][18][19] Mouse BV2 microglial cells (LPS-induced) Anthocyanins ↓ NO, PGE2, TNF-α and IL-1β release, iNOS and COX-2 expressions, NF-κB nuclear translocation [20,21] Mouse microglial cells (LPS/IFN-γ-induced) Anthocyanins ↓ NO and TNF-α release, iNOS expression [22] Rat HAPI microglial cells (LPS-induced) Tart cherry extract ↓ NO and TNF-α release, COX-2 expression; ↔ iNOS expression [23] Rat astrocytes (LPS-induced) Lingonberry extract ↓ ROS production [24] Animal Mouse model (PD) GSSE ↓ ROS production, inflammatory markers [25] Mouse model (LPS and Aβ-induced microglia neuroinflammation) RES ↓ TLR4, NF-κB and cytokine secretion [26] Mouse model (LPS-impaired adult hippocampal neurogenesis) EGCG ↓ TLR4 signaling [27] Mouse model (LPS-treated) Anthocyanins ↓ NF-kB, TNF-α, and IL-1β levels [28] Mouse model (LPS-treated) PSPC ↓ TNF-α, IL-6 and IL-1β overproduction, NF-kB activation [29] Mouse model (LPS-treated) Anthocyanins ↓ ROS production, NF-kB activation, TNF-α, and IL-1β levels [30] Mouse model (LPS-treated) Anthocyanins ↓ TNF-α, and IL-1β increase; ↑ IL-10 expression [31] Mouse model (high-fat diet) PSPC ↓ iNOS, COX-2, TNF-α, IL-1β and IL-6 expressions, p38 MAPK and NF-kB activation; ↑ IL-10 levels [32] Rat model (MCAO/R) Anthocyanins ↓ TNF-α, IL-6 and IL-1β levels, NF-kB and NLRP3 expressions [33] Human Subjects with AD RES ↓ plasma pro-inflammatory markers [34] ↑: increase; ↓: decrease; ↔: insignificant change; Aβ: beta-amyloid; AD: Alzheimer's disease; COX: cyclooxygenase; EGCG: epigallocatechin gallate; GSSE: grape seed and skin extract; IFN-γ: interferon gamma; IL: interleukin; iNOS: inducible nitric oxide synthase; LDL: low-density lipoprotein; LPS: lipopolysaccharide; MAPK: mitogen-activated protein kinase; MCAO/R: middle cerebral artery occlusion/reperfusion; NF-κB: nuclear factor kappa B; NLRP: NOD-like receptor protein; NO: nitric oxide; ox: oxidized; PBMC: peripheral blood mononuclear cell; PD: Parkinson's disease; PGE2: prostaglandin E2; PSPC: purple sweet potato color; RES: resveratrol; ROS: reactive oxygen...…”

“…In a human astrocyte study, the secretion of IL-6 was reduced at low doses of LPS and anthocyanins [16]. However, in the absence of LPS, IL-6 secretion increased when treated with high concentration of anthocyanin, suggesting antioxidant toxicity with a single compound supplementation [16]. Some studies have highlighted that the synergistic effects of mixed polyphenols provided better outcomes than single compound supplementation.…”

Saccharomyces cerevisiae cells lacking transcription factors Skn7 or Yap1 exhibit different susceptibility to cyanidin

“…The studies on anthocyanins deal mainly with their chemoprotective action owed to the antioxidant capacity which is conferred by the anthocyanidin moiety ( Tedesco et al., 2001 ; Heo and Lee 2005 ; Isaak et al., 2017 ) and it is widely believed that the toxicity of anthocyanins is very low ( Wallace and Giusti 2015 ). Studies on the potential toxicity of anthocyanins/anthocyanidins are less represented, although some alarm has been triggered concerning their role in the so called ‘antioxidative stress’, which can be correlated with overconsumption of natural antioxidants, either in complex mixtures or as single isolated compounds ( Poljsak and Milisav 2012 ; Kwee 2014 ; Cai et al., 2018 ; Cásedas et al., 2019 ). Although it is considered that the ingestion of an isolated natural compound carries less risk comparing with a complex natural mixture, not many isolated polyphenols have been subjected to rigorous testing ( Cásedas et al., 2019 ).…”

“…Studies on the potential toxicity of anthocyanins/anthocyanidins are less represented, although some alarm has been triggered concerning their role in the so called ‘antioxidative stress’, which can be correlated with overconsumption of natural antioxidants, either in complex mixtures or as single isolated compounds ( Poljsak and Milisav 2012 ; Kwee 2014 ; Cai et al., 2018 ; Cásedas et al., 2019 ). Although it is considered that the ingestion of an isolated natural compound carries less risk comparing with a complex natural mixture, not many isolated polyphenols have been subjected to rigorous testing ( Cásedas et al., 2019 ). We therefore decided to investigate the potential toxicity of pure cyanidin on Saccharomyces cerevisiae cells, and while no apparent toxicity was recorded on the wild type, it was noted that the cells devoid of the transcription factors Skn7 or Yap1 exhibited different sensitivity to cyanidin exposure.…”