Table 4.
Metabolic Targets of Piceatannol
| Model | Target and effect | Putative role | Ref. |
|---|---|---|---|
| Murine adipocytes (3T3-L1) | Inhibited adipogenesis, blocked mitotic clonal expansion, inhibited insulin signaling due to noncompetitive binding to insulin receptor, lowered lipid accumulation during late stages of differentiation | Antiadipogenic | 36 |
| Human liposarcoma preadipocytes (LiSa-2) | Induced CHOP expression, inhibited adipocyte differentiation as demonstrated by lack of lipid accumulation | Antiadipogenic | 37 |
| Human liposarcoma adipocytes (LiSa-2) | Induced CHOP expression, reduced VEGF production | Antiadipogenic | 37 |
| Mouse (C57BL/6) WAT | Lowered PPARγ and FAS protein expression, increased AMPKα, PPARα, and CPT1-α protein expression and ACC phosphorylation | Antiadipogenic, antilipogenic | 45 |
| Mouse (C57BL/6) liver | Lowered PPARγ, C/EBPα, and FAS protein expression, increased AMPKα and ACC phosphorylation, | Antiadipogenic, antilipogenic | 45 |
| Murine adipocytes (3T3-L1) | Lowered TG accumulation, lipid droplet accumulation | Antilipogenic | 41 |
| Murine adipocytes (3T3-L1) | Lowered TG accumulation | Antilipogenic | 44 |
| HUVECs | Inhibited ATP synthesis | Antilipogenic | 42 |
| Rat brain mitochondrial fractions | Inhibited F0F1-ATPase | Antilipogenic | 79 |
| Recombinant, full-length human holocarboxylase synthase | Inhibited holocarboxylase synthase | Antilipogenic | 80 |
| Rat myoblasts (L6) | Increased glucose uptake, increased AMPK phosphorylation and GLUT4 translocation | Glucose handling improvement | 46 |
| Yeast α-glucosidase | Inhibited α-glucosidase activity | Glucose handling improvement | 81 |
| Murine subcutaneous adipocytes | Impaired insulin-stimulated lipogenesis, inhibited basal and stimulated glycerol and FFA release | Antilipolytic | 43 |
| Primary human osteoarthritic osteoblasts | Inhibited alkaline phosphatase activity, carboxy-terminal propeptide of collagen type 1 production, lowered TGF-β1 expression | Leptin signaling | 48 |
| Human adipose tissue | Lowered H2O2 production, inhibited tyramine- and benzylamine-induced H2O2 production, inhibited [14C]-tyramine oxidation | Antioxidant | 43 |
| Rat liver microsomes | Increased oxygen consumption | Antioxidant | 27 |
| WAT explants from obese Zucker rats | Lowered amine-induced hydrogen peroxide generation | Antioxidant | 44 |
| HUVECs | Increased expression and activity of HO-1 through Nrf2; decreased IL-6, TNF-α, ROS formation, p-65 phosphorylation, NF-κB activation in palmitic acid-induced inflammation; restored IRS-1 phosphorylation, eNOS phosphorylation in palmitic acid-induced inflammation through HO-1 | Anti-inflammatory | 53 |
| Bone marrow-derived macrophages | Restored HO-1 mRNA and protein expression after RANKL inhibition, decreased miR-183 | Anti-inflammatory | 59 |
| Human mammary epithelial cells (MCF10A) | Upregulated HO-1 mRNA and protein expression, decreased Keap1 levels, increased Nrf2 translocation, increased Akt activation | Anti-inflammatory | 61 |
| Rat liver | Increased HO-1 expression and Akt activation, reduced trauma-induced IL-6, ICAM-1, CINC-1, and CINC-3 levels | Anti-inflammatory | 62 |
| Murine neuronal cells (HT22) | Reduced glutamate-induced toxicity and ROS production, increased HO-1 expression and activity, induced Nrf2 activation | Anti-inflammatory, antioxidant | 63 |
| Murine macrophages (RAW264.7) | Decreased LPS-induced TNF-α and IL-1β levels, induced HO-1 expression | Anti-inflammatory | 58 |
| Bovine aortic endothelial cells | Increased HO-1 protein and mRNA expression | Anti-inflammatory | 60 |
| Murine macrophages (RAW264.7) | Decreased LPS-induced NO release and iNOS expression; prevented LPS-induced degradation of κBα, p65 translocation, STAT3 phosphorylation and translocation; increased HO-1 protein and mRNA expression | Anti-inflammatory | 65 |
| Human lymphoma (RAMOS) cells | Inhibited STAT3 and STAT5 phosphorylation | Anti-inflammatory | 67 |
| Human lymphocytes (Jurkat T cells) | Inhibited Jak1 and IFNAR1 tyrosine phosphorylation | Anti-inflammatory | 67 |
| human prostate cancer (DU145) cells | Inhibited STAT3 phosphorylation, IL-6 secretion | Anti-inflammatory | 66 |
| Human astrocytoma (U373) cells | Inhibited LPS-induced IRF3 activation, ISG induction, and TNF-α, ICAM-1, and MCP-1 upregulation | Anti-inflammatory | 74 |
| Murine macrophages (RAW264.7) | Inhibited LPS-induced IL-6 upregulation | Anti-inflammatory | 74 |
| Swiss mice | Prevented LPS-induced septic shock and liver and spleen damage | Anti-inflammatory | 74 |
| HUVECs | Inhibited CT-1-induced IL-6 mRNA and protein expression | Anti-inflammatory | 70 |
| Murine microglia (BV2) cells | Inhibited LPS-induced NO release, PGE2 release, iNOS expression, COX-2 mRNA and protein expression, NF-κB activity, p65 translocation, IL-1β levels, IL-6 levels, and TNF-α levels, | Anti-inflammatory | 71 |
| Peripheral blood mononuclear cell | Lowered OK-432-stimulated (penicillin-killed Streptococcus pyogenes) IL-6 and TNF-α secretion and mRNA expression | Anti-inflammatory | 69 |
| Human peripheral blood mononuclear leukocytes | Inhibited PGE2 levels, Lowered LPS and IFN-γ-stimulated TNF-α, IL-8 levels, and COX-2, TNF-α, IL-8, IL-6, IL-1α mRNA expression | Anti-inflammatory | 72 |
| Human monocytes (mono Mac 6) | Inhibited LPS-stimulated IL-6 levels | Anti-inflammatory | 68 |
| Human bronchial epithelial cells | Inhibited TNF-α-induced ICAM-1 expression and IL-6 release | Anti-inflammatory | 73 |
| Human myeloid cells (KBM-5) | Lowered TNF-α, PMA, LPS, okadic acid, ceramide, and H2O2-induced NF-κB activation; inhibited TNF-α-induced IκBα phosphorylation, IKK activation, and p65 phosphorylation and translocation | Anti-inflammatory | 82 |
| Human lymphocytes (Jurkat T cells) | Lowered TNF-α-induced NF-κB activation | Anti-inflammatory | 82 |
| Epithelial cells (MCF-7, HeLa) | Lowered TNF-α-induced NF-κB activation | Anti-inflammatory | 82 |
| Human monocytic (THP-1) cells | Upregulated SIRT1 mRNA and protein expression | SIRT activation | 83 |
| HeLa cells | Stimulated SIRT1 activity | SIRT activation | 84 |
| Human hepatoma (HepG2) cells | Increased SIRT1 expression, decreased c-Myc, β-catenin, and PHD2 expression | SIRT activation | 85 |
AMPK, 5′ AMP-activated protein kinase; eNOS, endothelial nitric oxide synthase; FFAs, free fatty acids; GLUT4, glucose transporter 4; HO-1, heme oxygenase-1; HUVEC, human umbilical vein endothelial cell; IL, interleukin; IRS-1, insulin receptor substrate-1; MCP-1, monocyte chemotactic protein-1; NF-κB, nuclear factor-κB; Nrf2, nuclear factor erythroid 2-related factor 2; ROS, reactive oxygen species; STAT3, signal transducer and activator of transcription factor-3; TG, triglyceride; TNF-α, tumor necrosis factor-alpha; WAT, white adipose tissue.