Phloretin, a dihydrochalcone flavonoid, can inhibit the active transport of glucose into cells by SGLT1 and SGLT2. It is mainly found in fruit and roots of apple tree.
Phloretin is a natural flavonoid with various bioactive properties. It inhibits monocarboxylate transporters MCT1 and MCT2 with IC50 values of 28 8µM and 14 2µM, respectively, thereby suppressing the transport of monocarboxylate across the plasma membrane[3]. Phloretin has also been shown to inhibit human concentrative nucleoside transporter 3 (Ki = 32.28µM) and sodium/D-glucose cotransporter (Ki = 86µM)[4]. Phloretin at 10 and 20µM significantly inhibited toll-like receptor 2/1 (TLR2/1) signaling in Raw264.7 cells by downregulating 37.2% and 66.1% of the Pam3CSK4-induced TNF-α production, respectively. In Pam3CSK4-activated HEK293-hTLR2 cells, one-hour pretreatment with phloretin (1 - 20μM) dose-dependently inhibited TNF-α production by 33.3% – 51.1%. Phloretin at 1 - 20μM also decreased the level of IL-8 by 23.2% – 73.4% in these cells. The treatment of Pam3CSK4-activated Raw 264.7 cells with phloretin (20 μM) suppressed the protein level of TLR2 by 75.1% as compared to the controls[5]. Daily administration of phloretin (50 and 100mg/kg) ameliorated collagen-induced arthritis in the hind-limbs of mice and inhibited the production of proinflammatory cytokines in mouse joints[6].
作用机制
Phloretin inhibits TLR2–TLR1 heterodimerization by directly binding to the interface of TLR2 and TLR1 at a shallower position compared to Pam3CSK4[5].
Phloretin 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
H1299 cells
Function assay
30 mins
Inhibition of GLUT1 in human H1299 cells assessed as inhibition of 2-deoxy-D-[3H]-glucose uptake incubated for 15 mins prior to 2-deoxy-D-[3H]-glucose addition measured after 30 mins by liquid scintillation counting analysis, IC50=21.4 Μm
24200808
PK15NTD cells
Function assay
Binding affinity to human recombinant CNT3 expressed in pig PK15NTD cells assessed as [3H]uridine uptake by beta-scintillation, Ki=32.28 μM
Inhibition of GLUT1 in human H1299 cells assessed as inhibition of 2-deoxy-D-[3H]-glucose uptake incubated for 15 mins prior to 2-deoxy-D-[3H]-glucose addition measured after 30 mins by liquid scintillation counting analysis, IC50=21.4 Μm
24200808
PK15NTD cells
Function assay
Binding affinity to human recombinant CNT3 expressed in pig PK15NTD cells assessed as [3H]uridine uptake by beta-scintillation, Ki=32.28 μM
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