Limits...
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

Effects of ARMs on LPS-stimulated NO and PGE2 production, and iNOS and COX-2 expressions in RAW264.7 cells. The samples of hepatic metabolites were made as described in the Materials and Methods section. Cells were treated with the standard concentration (A; 20 μM) and hepatic metabolites of apigenin (AMs; 20 μM), hepatic metabolites of apigenin (20 μM) and resveratrol (10, 20 and 40 μM) (ARMs 1:0.5, 1:1 and 1:2), and hepatic metabolites of resveratrol (40 μM) for 30 min, and then incubated in the presence of LPS (1 μg/mL) for 18 h. (A) Nitrite accumulation was measured as described in the Materials and Methods section; (B) PGE2 production was measured as described in the Materials and Methods section. Data were presented as means ± SEM and were representative of triplicate experiments: *p < 0.05 compared to cells cultured with LPS (1 μg/mL) alone; # p < 0.05 compared to cells cultured with LPS (1 μg/mL) and AMs; (C) The expression of iNOS and COX-2 were examined by Western blot analysis.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4663613&req=5

nutrients-07-05485-f002: Effects of ARMs on LPS-stimulated NO and PGE2 production, and iNOS and COX-2 expressions in RAW264.7 cells. The samples of hepatic metabolites were made as described in the Materials and Methods section. Cells were treated with the standard concentration (A; 20 μM) and hepatic metabolites of apigenin (AMs; 20 μM), hepatic metabolites of apigenin (20 μM) and resveratrol (10, 20 and 40 μM) (ARMs 1:0.5, 1:1 and 1:2), and hepatic metabolites of resveratrol (40 μM) for 30 min, and then incubated in the presence of LPS (1 μg/mL) for 18 h. (A) Nitrite accumulation was measured as described in the Materials and Methods section; (B) PGE2 production was measured as described in the Materials and Methods section. Data were presented as means ± SEM and were representative of triplicate experiments: *p < 0.05 compared to cells cultured with LPS (1 μg/mL) alone; # p < 0.05 compared to cells cultured with LPS (1 μg/mL) and AMs; (C) The expression of iNOS and COX-2 were examined by Western blot analysis.

Mentions: As shown in Figure 2A and B, addition of apigenin significantly suppressed production of NO and PGE2 in LPS-stimulated RAW cells; otherwise addition of AMs and RMs showed no distinctive NO and PGE2 suppressing activity indicating that potent anti-inflammatory activities of apigenin might become weakened after metabolization in hepatocytes. When apigenin was co-metabolized with resveratrol (ARMs) and examined for NO and PGE2 suppressing activity, however, production of NO and PGE2 was suppressed in the order of increased concentrations of resveratrol in ARMs (p < 0.05). These results suggested that co-metabolization of resveratrol with apigenin recover to a certain degree anti-inflammatory activity of apigenin after hepatic metabolism.


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

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

Effects of ARMs on LPS-stimulated NO and PGE2 production, and iNOS and COX-2 expressions in RAW264.7 cells. The samples of hepatic metabolites were made as described in the Materials and Methods section. Cells were treated with the standard concentration (A; 20 μM) and hepatic metabolites of apigenin (AMs; 20 μM), hepatic metabolites of apigenin (20 μM) and resveratrol (10, 20 and 40 μM) (ARMs 1:0.5, 1:1 and 1:2), and hepatic metabolites of resveratrol (40 μM) for 30 min, and then incubated in the presence of LPS (1 μg/mL) for 18 h. (A) Nitrite accumulation was measured as described in the Materials and Methods section; (B) PGE2 production was measured as described in the Materials and Methods section. Data were presented as means ± SEM and were representative of triplicate experiments: *p < 0.05 compared to cells cultured with LPS (1 μg/mL) alone; # p < 0.05 compared to cells cultured with LPS (1 μg/mL) and AMs; (C) The expression of iNOS and COX-2 were examined by Western blot analysis.
© Copyright Policy
Related In: Results  -  Collection

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

nutrients-07-05485-f002: Effects of ARMs on LPS-stimulated NO and PGE2 production, and iNOS and COX-2 expressions in RAW264.7 cells. The samples of hepatic metabolites were made as described in the Materials and Methods section. Cells were treated with the standard concentration (A; 20 μM) and hepatic metabolites of apigenin (AMs; 20 μM), hepatic metabolites of apigenin (20 μM) and resveratrol (10, 20 and 40 μM) (ARMs 1:0.5, 1:1 and 1:2), and hepatic metabolites of resveratrol (40 μM) for 30 min, and then incubated in the presence of LPS (1 μg/mL) for 18 h. (A) Nitrite accumulation was measured as described in the Materials and Methods section; (B) PGE2 production was measured as described in the Materials and Methods section. Data were presented as means ± SEM and were representative of triplicate experiments: *p < 0.05 compared to cells cultured with LPS (1 μg/mL) alone; # p < 0.05 compared to cells cultured with LPS (1 μg/mL) and AMs; (C) The expression of iNOS and COX-2 were examined by Western blot analysis.
Mentions: As shown in Figure 2A and B, addition of apigenin significantly suppressed production of NO and PGE2 in LPS-stimulated RAW cells; otherwise addition of AMs and RMs showed no distinctive NO and PGE2 suppressing activity indicating that potent anti-inflammatory activities of apigenin might become weakened after metabolization in hepatocytes. When apigenin was co-metabolized with resveratrol (ARMs) and examined for NO and PGE2 suppressing activity, however, production of NO and PGE2 was suppressed in the order of increased concentrations of resveratrol in ARMs (p < 0.05). These results suggested that co-metabolization of resveratrol with apigenin recover to a certain degree anti-inflammatory activity of apigenin after hepatic metabolism.

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