Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin

Genes & Nutrition

Table 1 Blood brain barrier penetration potential of fisetin

Compound	A–B	B–A	Efflux	BBB penetration potential
Fisetin	18.0	1.33	0.1	High
Caffeine^a	20.2	22.2	1.1	High
Atenolol^a	0.13	0.25	1.9	Low

The potential for blood brain barrier penetration was determined using MDR1-MDCK cell monolayers as described [93]. MDR-MDCK cells plated at 60,000 cells/cm² on collagen-coated, microporous polycarbonate membranes in 12-well transwell plates were grown for 7–11 days. The quality of the monolayer was verified by TEER measurement (>1,400). The test compounds at a final concentration of 5 μM in HBSS were added to the apical or basolateral side and aliquots removed for analysis from the opposite side at 30 min intervals over 2 h. The concentrations of the compounds in the samples were determined by LC/MS/MS. The potential for BBB penetration is viewed as high if Papp A → B ≥ 3.0 × 10⁻⁶ cm/s and efflux < 3.0, moderate if Papp A → B ≥ 3.0 × 10⁻⁶ cm/s and 10 > efflux ≥ 3.0 and low if Papp A → B ≥ 3.0 × 10⁻⁶ cm/s and efflux ≥ 10 or Papp A → B < 3.0 × 10⁻⁶ cm/s. Results for caffeine and atenolol, CNS positive and negative compounds, respectively, are shown for comparison
^aFrom Wang et al. [93]

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