Progress 09/01/03 to 08/31/06
Outputs
Cornelian cherries (Cornus mas) are used in the preparation of beverages in Europe and also to treat diabetes related disorders in Asia. Anthocyanins are responsible for a variety of bright colors including red, blue, and purple in fruits, vegetables, and flowers and consumed as dietary polyphenols. Anthocyanin containing fruits are implicated in decreased coronary heart diseases and used in antidiabetic preparations. We have characterized and quantified anthocyanins in the fruits of a number of Cornus spp. In addition, we have purified the most abundant bioactive compounds in C. mas fruits, the anthocyanins, cyanidin-3-glucoside, delphinidin-3-glucoside, cyanidin-3-galactoside and pelargonidin-3-galactoside, and ursolic acid. We have determined in vitro ability of these anthocyanins and several anthocyanidins, cyanidin, delphinidn, pelargonidin, malvidin, and petunidin to stimulate insulin secretion by rodent pancreatic beta cells. The compounds were tested in the
presence of 4 and 10 mM glucose concentrations. Our results indicated that cyanidin-3-glucoside and delphindin-3-glucoside were the most effective insulin secretagogues among the anthocyanins and anthocyanidins tested at 4 and 10 mM glucose concentrations. Pelargonidin-3-galactoside is one of the major anthocyanins and its aglycone, pelargonidin, caused a 1.4-fold increase in insulin secretion at 4 mM glucose concentration. Rest of the anthocyanins and anthocyanidins tested in our in vitro assay had only marginal affects on insulin secretion at 4 and 10 mM glucose concentrations. We have then determined the antiobese and insulin secretion abilities of C. mas anthocyanins, delphinidin, cyanidin and pelargonidin-3-O-galactosides, in C57BL/6J mouse model. Much attention has been focused on food that may be beneficial in preventing diet-induced body fat accumulation and possibly reduce the risk of diabetes and heart disease. Cornelian cherries (Cornus mas) are used in the preparation of
beverages in Europe and also to treat diabetes related disorders in Asia. Therefore, we have purified the most abundant bioactive compounds in C. mas fruits, the anthocyanins and ursolic acid, and evaluated their ability to ameliorate obesity and insulin resistance in mice fed a high fat diet. Mice were initially fed a high fat diet for four weeks and then switched to a high fat diet containing anthocyanins (1g/Kg high fat diet) and ursolic acid (500 mg/Kg high fat diet) for an additional 8 weeks. High fat diet induced glucose intolerance was prevented by anthocyanins and ursolic acid. The anthocyanins treated mice showed a 24% decrease in weight gain. These mice also showed decreased lipid accumulation in the liver including a significant decrease in liver triacylglycerol levels. Anthocyanins and ursolic acid treated mice exhibited extremely elevated insulin levels. Both treatments, however, showed preserved islet architecture and insulin staining. Overall, these data suggest that
anthocyanins and ursolic acid purified from C. mas fruits have biological activities that improve certain metabolic parameters associated with diets high in saturated fats and obesity and regulate blood glucose.
Impacts
Our results suggest that consumption of Cornus mas fruits has potential to reduce overall body weight under obese conditions. In addition, a decrease in total cholesterol and triglycerides and improved insulin secretion by pancreatic beta cells are other potential benfits of C. mas fruits to diabetic patients.
Publications
- Vareed, S.K., Reddy,M.K., Schutzki, R.E., Nair, M.G. 2006. Tumor cell growth inhibitory anthocyanins in Cornus alternifolia, Cornus controversa, Cornus kousa and Cornus florida fruits. Life Sciences. 78: 777-784.
- Bolleddula,J., Olson,L.K., Schutzki,R.E., Tai, M-H.,Nair, M.G. 2006. Amelioration of obesity and glucose intolerance in high fat fed C57BL/6 mice by anthocyanins and ursolic acid in Cornelian cherry (Cornus mas). J. Agric. Food Chemistry. 54: 243-248.
- Vareed, S.K., Schutzki, R.E., Nair, M.G. 2006. Lipid peroxidation, cyclooxygenase enzyme and tumor cell proliferation inhibitory compounds in Cornus kousa. Phytomedicine. In Press.
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Progress 01/01/05 to 12/31/05
Outputs
We have completed the isolation of anthocyanins in Cornus mas fruits collected in November of 2004. Anthocyanin containing fruits are implicated in decreased coronary heart diseases and used in antidiabetic preparations. In the present study, we have determined the antiobese and insulin secretion abilities of C. mas anthocyanins, delphinidin, cyanidin and pelargonidin-3-O-galactosides, in C57BL/6J mouse model. Much attention has been focused on food that may be beneficial in preventing diet-induced body fat accumulation and possibly reduce the risk of diabetes and heart disease. Cornelian cherries (Cornus mas) are used in the preparation of beverages in Europe and also to treat diabetes related disorders in Asia. Therefore, we have purified the most abundant bioactive compounds in C. mas fruits, the anthocyanins and ursolic acid, and evaluated their ability to ameliorate obesity and insulin resistance in C57BL/6 mice fed a high fat diet. Mice were initially fed a high
fat diet for four weeks and then switched to a high fat diet containing anthocyanins (1g/Kg high fat diet) and ursolic acid (500 mg/Kg high fat diet) for an additional 8 weeks. High fat diet induced glucose intolerance and this was prevented by anthocyanins and ursolic acid. The anthocyanins treated mice showed a 24% decrease in weight gain. These mice also showed decreased lipid accumulation in the liver including a significant decrease in liver triacylglycerol concentration. Anthocyanins and ursolic acid treated mice exhibited extremely elevated insulin levels. Both treatments, however, showed preserved islet architecture and insulin staining. Overall, these data suggest that anthocyanins and ursolic acid purified from C. mas fruits have biological activities that improve certain metabolic parameters associated with diets high in saturated fats and obesity (this abstract and the full manuscript are in press, J. Agric. Food Chem.).
Impacts
Our results suggest that consumption of Cornus mas fruits has potential to reduce overall body weight under obese conditions. In addition, a decrease in total cholesterol and triglycerides and improved insulin secretion by pancreatic beta cells are other potential benfits of C. mas fruits to diabetic patients.
Publications
- Bolleddula, J., Vareed, S.K., Olson, L.K., Nair, M.G. 2005. Insulin secretion by bioactive anthocyanins and anthocyanidins present in fruits. J. Agric. Food Chem. 53: 28-31.
- Zhang, Y., Vareed, S.K., Nair, M.G. 2005. Human tumor cell growth inhibition by nontoxic anthocyanidins, the pigments in fruits and vegetables. Life Sciences. 76: 1465-1472.
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Progress 01/01/04 to 12/31/04
Outputs
We have completed the extraction of Cornus mas fruits collected in October-November of 2003. We have also collected additional C. mas fruits in November of 2004. The fresh fruits were pitted manually. The pits were dried and extracted sequentially with hexane, ethyl acetate and methanol. The seedless fruits were blended with RO water and centrifuged. The aqueous extract was lyophilized. The residue was extracted with methanol and ethyl acetate, respectively, and the solvents evaporated under reduced pressure. The aqueous, methanol and ethyl acetate extracts of the fruits and the seed extracts were investigated for insulin secretion activity in vivo using rodent pancreatic beta cells. The aqueous and ethyl acetate extracts induced secretion of insulin and hence were purified. The aqueous extract predominantly contained anthocyanins, sugars and acids. The acids and sugars were removed and the anthocyanin fraction was evaluated in vitro for insulin secretion.
Anthocyanins are responsible for a variety of bright colors including red, blue, and purple in fruits, vegetables, and flowers and consumed as dietary polyphenols. Anthocyanin containing fruits are implicated in decreased coronary heart diseases and used in antidiabetic preparations. In the present study, we have determined the ability of anthocyanins, cyanidin-3-glucoside, delphinidin-3-glucoside, cyanidin-3-galactoside and pelargonidin-3-galactoside; and anthocyanidins, cyanidin, delphinidn, pelargonidin, malvidin, and petunidin to stimulate insulin secretion by rodent pancreatic beta cells. The compounds were tested in the presence of 4 and 10 mM glucose concentrations. Our results indicated that cyanidin-3-glucoside and delphindin-3-glucoside were the most effective insulin secretagogues among the anthocyanins and anthocyanidins tested at 4 and 10 mM glucose concentrations. Pelargonidin-3-galactoside is one of the major anthocyanins and its aglycone, pelargonidin, caused a
1.4-fold increase in insulin secretion at 4 mM glucose concentration. Rest of the anthocyanins and anthocyanidins tested in our assay had only marginal affects on insulin at 4 and 10 mM glucose concentrations. Animal studies using C57BL/KsJ are in progress. These mice are mutants of leptin-receptor and prone to develop hyperphagia, obesity, hyperinsulinemia and hyperglycemia. The in vivo effect of Cornus fruits and its components are being evaluated at the moment. Animal studies using C57BL/KsJ mice are in progress. These mice are mutants of leptin-receptor and prone to develop hyperphagia, obesity, hyperinsulinemia and hyperglycemia. The effect of Cornus fruits and its components are being evaluated at eh moment. Patent/Invention Serial No. 60/591,806. DATE: July 29,2004.
Impacts
If the project is successful, there is potential for compounds from Cornus mas fruits that could be used as phytomedicine to prevent or treat type-2 diabetes.
Publications
- No publications reported this period
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Progress 01/01/03 to 12/31/03
Outputs
This project started in September of 2003. We have completed the collection of Cornus mas fruits in October-November. Year 2003 is not a very good year for C. mas fruits in Michigan. We have also completed the extraction of 2 kg of C. mas fruits. The fresh fruits were pitted manually. The pits were dried and extracted sequentially with hexane, ethyl acetate and methanol. The seedless fruits were blended with RO water and centrifuged. The aqueous extract was lyophilized. The residue was extracted with methanol and ethyl acetate, respectively, and the solvents evaporated under reduced pressure. The aqueous, methanol and ethyl acetate extracts of the fruits and the seed extracts are under investigation for insulin secretion activity in vivo using rodent pancreatic beta cells (INS-1). We are also in the process of housing mice to start the blood glucose level experiments with Cornus mas extracts. The extracts will be administered to the mice IP as DMSO solutions.
Impacts
If the project is successful, there is potential for compounds from Cornus mas fruits that could be used as phytomedicine to prevent or treat type-2 diabetes.
Publications
- We have just started this project in September of 2003. No publications are available at the moment.
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