Vol. 38, No. 4629 Biol. Pharm. Bull. 38, 629–633 (2015)
Note
Piceatannol Lowers the Blood Glucose Level in Diabetic Mice Hiroko Uchida-Maruki, Hiroyuki Inagaki, Ryouichi Ito, Ikuko Kurita, Masahiko Sai,* and Tatsuhiko Ito Health Science Research Center, Morinaga & Co., Ltd.; 2–1–1 Shimosueyoshi, Tsurumi-ku, Yokohama 230–8504, Japan. Received January 5, 2015; accepted February 3, 2015 We previously found that passion fruit (Passiflora edulis) seeds contained a high amount of piceatannol (3,5,3′,4′-trans-tetrahydroxystilbene), a natural analog of resveratrol (3,5,4′-trans-trihydroxystilbene). Resveratrol has been proposed as a potential anti-metabolic disorder compound, by its activation of sirtuin and AMP-activated protein kinase. Many reports show that resveratrol ameliorates diet-induced obesity and insulin resistance. However, it is not known whether piceatannol also affects diet-induced obesity. We explored the effect of piceatannol on high fat diet-fed mice. The results showed that piceatannol did not affect high fat diet-induced body weight gain or visceral fat gain in mice. However, piceatannol did reduce fasting blood glucose levels. Furthermore, to explore the potential of passion fruit seed extract containing piceatannol as a functional food, passion fruit seed extract was administered in a genetic diabetic mouse model (db/db mice). Single administration of passion fruit seed extract, as well as piceatannol reduced the blood glucose levels of these db/db mice. These results suggest that piceatannol and passion fruit seed extract may have potential application in the prevention of diabetes. Key words
piceatannol; passion fruit seed; antidiabetic activity; high fat diet; db/db
The incidence of metabolic syndrome is increasing worldwide due to aging and changes in lifestyle. In particular, this increase is largely attributed to the rise in the prevalence of obesity, and this common metabolic disorder is associated with increased risk of cardiovascular diseases and type II diabetes, and the latter substantially decreases quality of life and increases health care costs. It is difficult to strictly control blood glucose levels over the long term, even though many anti-diabetic medications are clinically available. Therefore, the development of functional foods that can prevent or improve type II diabetes is an urgent matter. Resveratrol is a natural component of several plants, including grapes, berries, and peanuts. Resveratrol displays widespread functions and has several health-promoting effects owing to its anti-cancer, anti-inflammation, and antioxidant activity.1) Recently, resveratrol has been proposed as a potential anti-metabolic syndrome compound because of its role in activating sirtuin and AMP-activated protein kinase (AMPK).2–5) Indeed, several studies have shown that resveratrol protects mice against diet-induced obesity.6–8) Resveratrol has also been shown to have a favorable effect on glucose metabolism in humans.9,10) However, it should be noted that no weight loss has been reported after resveratrol treatment in any human study.11) Piceatannol is a hydroxylated analog of resveratrol and is also found in various plants, including grapes and rhubarb. Although piceatannol shows activities similar to resveratrol, its levels in plants are significantly lower than those of resveratrol,12) and it has therefore received far less research attention. We previously found that passion fruit seeds have a high piceatannol content,13) and that piceatannol displays various properties such as sirtuin induction activity,14) vasorelaxant effect,15) upregulation of endothelial nitric oxide synthase expression,16) promotion of collagen synthesis, inhibition of melanogenesis,13) and protection of the skin from UVB ir-
radiation.17) Piceatannol shows much higher activity than resveratrol in some cases13,16); however, its effects on metabolic syndrome remain unknown. Therefore, we explored the effect of piceatannol on high-fat diet (HFD)-induced obese mice. Furthermore, to explore the possibility of passion fruit seed extract (PFSE) as a functional food, PFSE and piceatannol were administered to genetically diabetic model mice (db/db mice). These results clarified the potential anti-diabetic effect of piceatannol and of high piceatannol-content PFSE.
MATERIALS AND METHODS Materials Piceatannol was obtained from Tokyo Chemical Industry, Co., Ltd. (Japan). Piceatannol was dissolved with 0.5% carboxymethyl cellulose (CMC) within 3 h before administration. Preparation of PFSE The purple passion fruit (Passiflora edulis) is native from southern Brazil through Paraguay to northern Argentina. PFSE (lot number PFSE-102) was prepared as follows. Freeze-dried and milled purple passion fruit seeds (Morinaga Co., Ltd., Japan) were refluxed at 80°C using 10-fold amount of 80% (v/v) ethanol for 120 min. After centrifugation, the supernatant was evaporated, and the solvent was removed by freeze-drying. The chemical profile of PFSE was previously reported.13,15) The concentration of piceatannol was measured using HPLC analysis as previously described,14) and this powder contained piceatannol (94.9 µg/mg) as a major polyphenol. PFSE was dissolved with 0.5% CMC containing 2 mg/mL or 10 mg/mL piceatannol within 3 h before administration. Effect of Piceatannol in HFD Mice Ten-week-old male C57BL/6Jjcl mice were obtained from Clea Japan Inc. (Japan). Animals were maintained under standard conditions (temperature 23±2°C, humidity 50±10%, 12 : 12-h light–dark cycle;
To whom correspondence should be addressed. e-mail: [email protected] * © 2015 The Pharmaceutical Society of Japan
630
Biol. Pharm. Bull.
Vol. 38, No. 4 (2015)
Fig. 1. Effect of Piceatannol Treatment on Body Weight (a), Food Intake (b), Subcutaneous Fat (c), Visceral Fat (d), Blood Glucose (e), and Blood Leptin (f) Levels C57BL/6Jjcl mice were fed the normal diet (ND) or the high-fat diet (HFD) for 5 weeks. Various doses of piceatannol were administered daily to HFD-fed mice. Data are shown as mean±S.E.M. (n=7–8). P1, P3, P10, P30: HFD with 1, 3, 10, and 30 mg/kg piceatannol administration, respectively. * p
Note
Piceatannol Lowers the Blood Glucose Level in Diabetic Mice Hiroko Uchida-Maruki, Hiroyuki Inagaki, Ryouichi Ito, Ikuko Kurita, Masahiko Sai,* and Tatsuhiko Ito Health Science Research Center, Morinaga & Co., Ltd.; 2–1–1 Shimosueyoshi, Tsurumi-ku, Yokohama 230–8504, Japan. Received January 5, 2015; accepted February 3, 2015 We previously found that passion fruit (Passiflora edulis) seeds contained a high amount of piceatannol (3,5,3′,4′-trans-tetrahydroxystilbene), a natural analog of resveratrol (3,5,4′-trans-trihydroxystilbene). Resveratrol has been proposed as a potential anti-metabolic disorder compound, by its activation of sirtuin and AMP-activated protein kinase. Many reports show that resveratrol ameliorates diet-induced obesity and insulin resistance. However, it is not known whether piceatannol also affects diet-induced obesity. We explored the effect of piceatannol on high fat diet-fed mice. The results showed that piceatannol did not affect high fat diet-induced body weight gain or visceral fat gain in mice. However, piceatannol did reduce fasting blood glucose levels. Furthermore, to explore the potential of passion fruit seed extract containing piceatannol as a functional food, passion fruit seed extract was administered in a genetic diabetic mouse model (db/db mice). Single administration of passion fruit seed extract, as well as piceatannol reduced the blood glucose levels of these db/db mice. These results suggest that piceatannol and passion fruit seed extract may have potential application in the prevention of diabetes. Key words
piceatannol; passion fruit seed; antidiabetic activity; high fat diet; db/db
The incidence of metabolic syndrome is increasing worldwide due to aging and changes in lifestyle. In particular, this increase is largely attributed to the rise in the prevalence of obesity, and this common metabolic disorder is associated with increased risk of cardiovascular diseases and type II diabetes, and the latter substantially decreases quality of life and increases health care costs. It is difficult to strictly control blood glucose levels over the long term, even though many anti-diabetic medications are clinically available. Therefore, the development of functional foods that can prevent or improve type II diabetes is an urgent matter. Resveratrol is a natural component of several plants, including grapes, berries, and peanuts. Resveratrol displays widespread functions and has several health-promoting effects owing to its anti-cancer, anti-inflammation, and antioxidant activity.1) Recently, resveratrol has been proposed as a potential anti-metabolic syndrome compound because of its role in activating sirtuin and AMP-activated protein kinase (AMPK).2–5) Indeed, several studies have shown that resveratrol protects mice against diet-induced obesity.6–8) Resveratrol has also been shown to have a favorable effect on glucose metabolism in humans.9,10) However, it should be noted that no weight loss has been reported after resveratrol treatment in any human study.11) Piceatannol is a hydroxylated analog of resveratrol and is also found in various plants, including grapes and rhubarb. Although piceatannol shows activities similar to resveratrol, its levels in plants are significantly lower than those of resveratrol,12) and it has therefore received far less research attention. We previously found that passion fruit seeds have a high piceatannol content,13) and that piceatannol displays various properties such as sirtuin induction activity,14) vasorelaxant effect,15) upregulation of endothelial nitric oxide synthase expression,16) promotion of collagen synthesis, inhibition of melanogenesis,13) and protection of the skin from UVB ir-
radiation.17) Piceatannol shows much higher activity than resveratrol in some cases13,16); however, its effects on metabolic syndrome remain unknown. Therefore, we explored the effect of piceatannol on high-fat diet (HFD)-induced obese mice. Furthermore, to explore the possibility of passion fruit seed extract (PFSE) as a functional food, PFSE and piceatannol were administered to genetically diabetic model mice (db/db mice). These results clarified the potential anti-diabetic effect of piceatannol and of high piceatannol-content PFSE.
MATERIALS AND METHODS Materials Piceatannol was obtained from Tokyo Chemical Industry, Co., Ltd. (Japan). Piceatannol was dissolved with 0.5% carboxymethyl cellulose (CMC) within 3 h before administration. Preparation of PFSE The purple passion fruit (Passiflora edulis) is native from southern Brazil through Paraguay to northern Argentina. PFSE (lot number PFSE-102) was prepared as follows. Freeze-dried and milled purple passion fruit seeds (Morinaga Co., Ltd., Japan) were refluxed at 80°C using 10-fold amount of 80% (v/v) ethanol for 120 min. After centrifugation, the supernatant was evaporated, and the solvent was removed by freeze-drying. The chemical profile of PFSE was previously reported.13,15) The concentration of piceatannol was measured using HPLC analysis as previously described,14) and this powder contained piceatannol (94.9 µg/mg) as a major polyphenol. PFSE was dissolved with 0.5% CMC containing 2 mg/mL or 10 mg/mL piceatannol within 3 h before administration. Effect of Piceatannol in HFD Mice Ten-week-old male C57BL/6Jjcl mice were obtained from Clea Japan Inc. (Japan). Animals were maintained under standard conditions (temperature 23±2°C, humidity 50±10%, 12 : 12-h light–dark cycle;
To whom correspondence should be addressed. e-mail: [email protected] * © 2015 The Pharmaceutical Society of Japan
630
Biol. Pharm. Bull.
Vol. 38, No. 4 (2015)
Fig. 1. Effect of Piceatannol Treatment on Body Weight (a), Food Intake (b), Subcutaneous Fat (c), Visceral Fat (d), Blood Glucose (e), and Blood Leptin (f) Levels C57BL/6Jjcl mice were fed the normal diet (ND) or the high-fat diet (HFD) for 5 weeks. Various doses of piceatannol were administered daily to HFD-fed mice. Data are shown as mean±S.E.M. (n=7–8). P1, P3, P10, P30: HFD with 1, 3, 10, and 30 mg/kg piceatannol administration, respectively. * p
