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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

Effects of co-administration of apigenin and resveratrol on carrageenan-induced paw edema in mice. (A) Percentage of carrageen-induced paw edema of control group (vehicle), apigenin administered (50 mg/kg body weight), resveratrol administered (25 mg/kg body weight), apigenin and resveratrol administered (50 and 25 mg/kg body weight), and indomethacin (10 mg/kg body weight). Data were expressed as means ± SEM, n = 5. *p < 0.05 compared to administration of apigenin; (B) HPLC chromatograms of plasma of control (up), apigenin administered (middle), and apigenin and resveratrol co-administered (down) groups. Plasma samples were collected and analyzed for apigenin and its metabolites 5 h after carrageenan injection.
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nutrients-07-05485-f004: Effects of co-administration of apigenin and resveratrol on carrageenan-induced paw edema in mice. (A) Percentage of carrageen-induced paw edema of control group (vehicle), apigenin administered (50 mg/kg body weight), resveratrol administered (25 mg/kg body weight), apigenin and resveratrol administered (50 and 25 mg/kg body weight), and indomethacin (10 mg/kg body weight). Data were expressed as means ± SEM, n = 5. *p < 0.05 compared to administration of apigenin; (B) HPLC chromatograms of plasma of control (up), apigenin administered (middle), and apigenin and resveratrol co-administered (down) groups. Plasma samples were collected and analyzed for apigenin and its metabolites 5 h after carrageenan injection.

Mentions: We next expanded upon the results of the anti-inflammatory activities from in vitro cell line experiments through the use of a carrageenan-induced paw edema mouse model. The increased mouse paw volume after injection of carrageenan indicated development of edema caused by inflammation. As shown in Figure 4A, oral administration of apigenin (50 mg/kg body weight) or resveratrol (25 mg/kg body weight) showed no edema suppressing activity. Co-administration of apigenin and resveratrol (50 and 25 mg/kg body weight, respectively), however, significantly decreased the paw volume down to that of the positive control (indomethacin; 10 mg/kg body weight). After the paw edema experiment, the plasma concentration of apigenin was determined (Figure 4B and Table 1). When apigenin was fed without resveratrol, it was mostly metabolized into its glucuronide conjugates. The plasma concentration of apigenin in the apigenin and resveratrol co-administered group (1084.600 ± 243.508 ng/mL), however, was substantially greater (2.39 fold) than that in the solely apigenin administered group (452.996 ± 155.857 ng/mL). This result indicates that resveratrol may increase absorption of apigenin or/and make apigenin less metabolized by the body, which could result in suppression of paw edema in the mice.


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

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

Effects of co-administration of apigenin and resveratrol on carrageenan-induced paw edema in mice. (A) Percentage of carrageen-induced paw edema of control group (vehicle), apigenin administered (50 mg/kg body weight), resveratrol administered (25 mg/kg body weight), apigenin and resveratrol administered (50 and 25 mg/kg body weight), and indomethacin (10 mg/kg body weight). Data were expressed as means ± SEM, n = 5. *p < 0.05 compared to administration of apigenin; (B) HPLC chromatograms of plasma of control (up), apigenin administered (middle), and apigenin and resveratrol co-administered (down) groups. Plasma samples were collected and analyzed for apigenin and its metabolites 5 h after carrageenan injection.
© Copyright Policy
Related In: Results  -  Collection

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

nutrients-07-05485-f004: Effects of co-administration of apigenin and resveratrol on carrageenan-induced paw edema in mice. (A) Percentage of carrageen-induced paw edema of control group (vehicle), apigenin administered (50 mg/kg body weight), resveratrol administered (25 mg/kg body weight), apigenin and resveratrol administered (50 and 25 mg/kg body weight), and indomethacin (10 mg/kg body weight). Data were expressed as means ± SEM, n = 5. *p < 0.05 compared to administration of apigenin; (B) HPLC chromatograms of plasma of control (up), apigenin administered (middle), and apigenin and resveratrol co-administered (down) groups. Plasma samples were collected and analyzed for apigenin and its metabolites 5 h after carrageenan injection.
Mentions: We next expanded upon the results of the anti-inflammatory activities from in vitro cell line experiments through the use of a carrageenan-induced paw edema mouse model. The increased mouse paw volume after injection of carrageenan indicated development of edema caused by inflammation. As shown in Figure 4A, oral administration of apigenin (50 mg/kg body weight) or resveratrol (25 mg/kg body weight) showed no edema suppressing activity. Co-administration of apigenin and resveratrol (50 and 25 mg/kg body weight, respectively), however, significantly decreased the paw volume down to that of the positive control (indomethacin; 10 mg/kg body weight). After the paw edema experiment, the plasma concentration of apigenin was determined (Figure 4B and Table 1). When apigenin was fed without resveratrol, it was mostly metabolized into its glucuronide conjugates. The plasma concentration of apigenin in the apigenin and resveratrol co-administered group (1084.600 ± 243.508 ng/mL), however, was substantially greater (2.39 fold) than that in the solely apigenin administered group (452.996 ± 155.857 ng/mL). This result indicates that resveratrol may increase absorption of apigenin or/and make apigenin less metabolized by the body, which could result in suppression of paw edema in the mice.

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