C OHgroup within the Bring. To decide whether or not structural determinants responsible for the observed inhibitory effects on pAkt within the present study matched published structural functions enhancing the polyphenols’ CA1 Inhibitors products antioxidant properties [43], each activities had been compared (Table three; extra facts are described in the discussion section).Table 3. Comparison in the proposed structureactivity options with regards to inhibitory effects on Aktphosphorylation (pAkt) determined in the present study using the antioxidant properties of polyphenols [43]. Functional Characteristic Double bond (C2=C3) OHgroup in ring A OHgroup in ring B OHgroup in ring C (3OH) Glycosyl group OMethyl group Inhibition of pAkt Increase Enhance Increase Reduce AbolishReverse Lower Antioxidant Activity Increase Increase Raise Boost Reduce Reduce Functional groups entailing divergent effects are marked in bold and red.three.three. Achievable Activation via BioTransformation The direct precursor compounds ()catechin and ellagic acid had been compared with their corresponding intestinal microbiotagenerated metabolites with regards to their in vitro inhibitory potential on pAkt Ser473. ()Catechin caused a slight statistically nonsignificant boost of Aktphosphorylation with 9 six (n = three; mean inhibition S.D.), though M1 ((3,4dihydroxyphenyl)valerolactone) exhibited no influence on pAkt (n = 1), and the methylated M2 ((3methoxy4hydroxyphenyl)valerolactone) tended to raise pAkt with 9 9 (n = 3). This impact was not statistically important and was not further investigated (Sprout Inhibitors products Figure five, panel A). In contrast, there was a clear distinction between the effects of ellagic acid and its microbial metabolites. Although ellagic acid had slightly effect on Aktphosphorylation (12 4 ; n = three), urolithin A exhibited a significant and reproducible inhibition (35 12 ; n = 6; p = 0.001 ). Other urolithins (urolithin B, C, D) showed no statistically considerable inhibitory effects on Aktphosphorylation and were not additional investigated (n = 1, Figure 5, panel B).Biomolecules 2019, 9,10 ofBiomolecules 2019, 9,(urolithin B, C, D) showed no statistically important inhibitory effects on Aktphosphorylation and had been not additional investigated (n = 1, Figure five, panel B).ten of(A)(B)Figure Investigation of prospective bioactivation of polyphenols by intestinal bacteria. bacteria. (A) Figure 5. five. Investigation aof a potential bioactivation of polyphenols by intestinal (A) ()Catechin ()Catechin was compared with its microbiotagenerated metabolites M1 and M2. ()Catechin triggered was compared with its microbiotagenerated metabolites M1 and M2. ()Catechin and M2 and M2 triggered nonsignificant (N.S.) slight increase in Aktphosphorylation, M1 showed no activity. (B) nonsignificant (N.S.) slight boost in Aktphosphorylation, M1 showed no activity. (B) Ellagic acid did Ellagic acid didn’t significantly influence the Akt. In contrast, its microbial metabolite urolithin not drastically influence the phosphorylation ofphosphorylation of Akt. In contrast, its microbial A metabolite urolithin A induced significant inhibition Aktphosphorylation in comparison with of induced a pronounced and statistically a pronounced and ofstatistically substantial inhibition control (Aktphosphorylation compared to handle ( p = 0.001, ellagicstandard deviation) and compared to p = 0.001, mean regular deviation) and compared to imply acid ( p = 0.005, oneway ANOVATukey ellagic acid ( p = 0.005, oneway ANOVATukey posthoc test). Other= three for ()catechin,.
