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Resveratrol as a Bioenhancer to Improve Anti-Inflammatory Activities of Apigenin.

Lee JA, Ha SK, Cho E, Choi I - Nutrients (2015)

Bottom Line: Co-administration of apigenin (50 mg/kg) and resveratrol (25 mg/kg) also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%).Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin.These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin's anti-inflammatory activities in the body.

View Article: PubMed Central - PubMed

Affiliation: Research Group of Nutraceuticals for Metabolic Syndrome, Korea Food Research Institute, 1201-62, Anyangpangyoro, Seongnam, Gyeonggi 463-746, Korea. 07636@kfri.re.kr.

ABSTRACT
The aim of this study was to improve the anti-inflammatory activities of apigenin through co-treatment with resveratrol as a bioenhancer of apigenin. RAW 264.7 cells pretreated with hepatic metabolites formed by the co-metabolism of apigenin and resveratrol (ARMs) in HepG2 cells were stimulated with lipopolysaccharide (LPS). ARMs prominently inhibited (p < 0.05) the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin (IL)-1β, IL-6 and TNF-α. Otherwise no such activity was observed by hepatic metabolites of apigenin alone (AMs). ARMs also effectively suppressed protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Co-administration of apigenin (50 mg/kg) and resveratrol (25 mg/kg) also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%). Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin. When the action of resveratrol on the main apigenin metabolizing enzymes, UDP-glucuronosyltransferases (UGTs), was investigated, resveratrol mainly inhibited the formation of apigenin glucuronides by UGT1A9 in a non-competitive manner with a Ki value of 7.782 μM. These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin's anti-inflammatory activities in the body.

No MeSH data available.


Related in: MedlinePlus

Inhibition of resveratrol towards UGT1A9-catalyzed apigenin glucuronidation (A) and kinetic profiles for formation of apigenin glucuronide in the presence of resveratrol by recombinant UGT1A9 (B and C). Recombinant UGT1A9 (5 μg of protein) was incubated with 5 to 40 μM apigenin and 2 mM UDPGA at 37 °C for 30 to 360 min in the presence (10, 20, and 40 μM) or absence of resveratrol. Data were represented as means ± SEM and were representative of triplicate experiments.
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nutrients-07-05485-f005: Inhibition of resveratrol towards UGT1A9-catalyzed apigenin glucuronidation (A) and kinetic profiles for formation of apigenin glucuronide in the presence of resveratrol by recombinant UGT1A9 (B and C). Recombinant UGT1A9 (5 μg of protein) was incubated with 5 to 40 μM apigenin and 2 mM UDPGA at 37 °C for 30 to 360 min in the presence (10, 20, and 40 μM) or absence of resveratrol. Data were represented as means ± SEM and were representative of triplicate experiments.

Mentions: When apigenin was conjugated with glucuronide by various human recombinant UGTs, UGT1A9 was found to be mostly responsible for apigenin glucuronide formation [10]. Therefore, we performed kinetic assays to determine patterns of action of resveratrol on apigenin glucuronide formation by UGT1A9. Resveratrol inhibited production of apigenin glucuronide with a Ki value of 7.782 ± 0.84 μM. The model of inhibition and inhibition kinetic constants of UGT1A9 were determined in the presence of various concentrations of apigenin and resveratrol. The inhibitory pattern of resveratrol on forming apigenin glucuronides by recombinant UGT1A9 was found to be noncompetitive. The Km for apigenin was 0.478 ± 0.02 μM (Figure 5 and Table 2).


Resveratrol as a Bioenhancer to Improve Anti-Inflammatory Activities of Apigenin.

Lee JA, Ha SK, Cho E, Choi I - Nutrients (2015)

Inhibition of resveratrol towards UGT1A9-catalyzed apigenin glucuronidation (A) and kinetic profiles for formation of apigenin glucuronide in the presence of resveratrol by recombinant UGT1A9 (B and C). Recombinant UGT1A9 (5 μg of protein) was incubated with 5 to 40 μM apigenin and 2 mM UDPGA at 37 °C for 30 to 360 min in the presence (10, 20, and 40 μM) or absence of resveratrol. Data were represented as means ± SEM and were representative of triplicate experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663613&req=5

nutrients-07-05485-f005: Inhibition of resveratrol towards UGT1A9-catalyzed apigenin glucuronidation (A) and kinetic profiles for formation of apigenin glucuronide in the presence of resveratrol by recombinant UGT1A9 (B and C). Recombinant UGT1A9 (5 μg of protein) was incubated with 5 to 40 μM apigenin and 2 mM UDPGA at 37 °C for 30 to 360 min in the presence (10, 20, and 40 μM) or absence of resveratrol. Data were represented as means ± SEM and were representative of triplicate experiments.
Mentions: When apigenin was conjugated with glucuronide by various human recombinant UGTs, UGT1A9 was found to be mostly responsible for apigenin glucuronide formation [10]. Therefore, we performed kinetic assays to determine patterns of action of resveratrol on apigenin glucuronide formation by UGT1A9. Resveratrol inhibited production of apigenin glucuronide with a Ki value of 7.782 ± 0.84 μM. The model of inhibition and inhibition kinetic constants of UGT1A9 were determined in the presence of various concentrations of apigenin and resveratrol. The inhibitory pattern of resveratrol on forming apigenin glucuronides by recombinant UGT1A9 was found to be noncompetitive. The Km for apigenin was 0.478 ± 0.02 μM (Figure 5 and Table 2).

Bottom Line: Co-administration of apigenin (50 mg/kg) and resveratrol (25 mg/kg) also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%).Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin.These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin's anti-inflammatory activities in the body.

View Article: PubMed Central - PubMed

Affiliation: Research Group of Nutraceuticals for Metabolic Syndrome, Korea Food Research Institute, 1201-62, Anyangpangyoro, Seongnam, Gyeonggi 463-746, Korea. 07636@kfri.re.kr.

ABSTRACT
The aim of this study was to improve the anti-inflammatory activities of apigenin through co-treatment with resveratrol as a bioenhancer of apigenin. RAW 264.7 cells pretreated with hepatic metabolites formed by the co-metabolism of apigenin and resveratrol (ARMs) in HepG2 cells were stimulated with lipopolysaccharide (LPS). ARMs prominently inhibited (p < 0.05) the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin (IL)-1β, IL-6 and TNF-α. Otherwise no such activity was observed by hepatic metabolites of apigenin alone (AMs). ARMs also effectively suppressed protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Co-administration of apigenin (50 mg/kg) and resveratrol (25 mg/kg) also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%). Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin. When the action of resveratrol on the main apigenin metabolizing enzymes, UDP-glucuronosyltransferases (UGTs), was investigated, resveratrol mainly inhibited the formation of apigenin glucuronides by UGT1A9 in a non-competitive manner with a Ki value of 7.782 μM. These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin's anti-inflammatory activities in the body.

No MeSH data available.


Related in: MedlinePlus