期刊论文详细信息
Diabetology & Metabolic Syndrome
Blood glucose lowering activity of aloe based composition, UP780, in alloxan induced insulin dependent mouse diabetes model
Qi Jia1  Lidia Brownell1  Mandee Pantier1  Brandon Corneliusen1  Jifu Zhao1  Mesfin Yimam1 
[1] Unigen, Inc, 3005 1st Ave, Seattle, WA, 98121, USA
关键词: Alloxan;    Chromones;    Aloe vera;    Insulin resistance;   
Others  :  803587
DOI  :  10.1186/1758-5996-6-61
 received in 2014-01-10, accepted in 2014-05-18,  发布年份 2014
PDF
【 摘 要 】

Background

There are a few nutritional approaches to address the increased needs of managing diabetic conditions. Previously it has been reported that UP780, a standardized composition of aloe chromone formulated with an aloe polysaccharide, has a significant impact in reducing HbA1C, fasting blood glucose, fructosamine and plasma insulin level in humans and improved impaired glucose and insulin resistance in high-fat diet-induced and db/db non-insulin dependent diabetic mouse models. Here we describe activity of UP780 and its constituents to improve insulin sensitivity in alloxan induced insulin dependent diabetic mouse model.

Materials and method

Insulin dependent diabetes was induced by administering a single intraperitoneal injection of alloxan monohydrate at a dose of 150 mg/kg to CD-1 mice. Aloesin (UP394) was formulated with an Aloe vera inner leaf gel powder polysaccharide (Qmatrix) to yield a composition designated UP780. Efficacy of oral administration of UP780 at 2000 mg/kg and its constituents (aloesin at 80 mg/kg and Qmatrix at 1920 mg/kg) were evaluated in this model. Glyburide, a sulfonylurea drug used in the treatment of type 2 diabetes, was used at 5 mg/kg as a positive control. Effect of UP780 on non-diabetic normal mice was also addressed.

Results

Mice administered intraperitoneal alloxan monohydrate developed progressive type-1 diabetes like symptom. After 4 weeks of daily oral administration, reductions of 35.9%, 17.2% and 11.6% in fasting blood glucose levels were observed for UP780, the UP780 Aloe vera inner leaf gel polysaccharide preparation without chromone (Qmatrix), and Aloesin (UP394), treated animals respectively, compared to vehicle treated animals. UP780 has no impact on blood glucose level of non-diabetic healthy mice. UP780 showed statistically significant improvement for blood glucose clearance in oral glucose tolerance tests. Similarly, enhanced improvement in plasma insulin level and statistically significant reduction in triglyceride level was also observed for animals treated with the composition.

Conclusion

These findings suggest that UP780, a chromone standardized Aloe based composition, could possibly be used as a natural supplement alternative to facilitate maintenance of healthy blood glucose levels.

【 授权许可】

   
2014 Yimam et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140708043158981.pdf 453KB PDF download
Figure 3. 21KB Image download
Figure 2. 43KB Image download
Figure 1. 20KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】
  • [1]Cohen IK, Diegelmann RF, Lindblad WJ: Wound Healing: Biochemical & Clinical Aspects. Philadelphia: Saunders; 1992.
  • [2]Grindlay D, Reynolds T: The Aloe vera phenomenon: a review of the properties and modern uses of the leaf parenchyma gel. J Ethnopharmacol 1986, 16:117-151.
  • [3]Hart LA, van Enckevort PH, van Dijk H, Zaat R, de Silva KT, Labadie RP: Two functionally and chemically distinct immunomodulatory compounds in the gel of Aloe vera. J Ethnopharmacol 1988, 23:61-71.
  • [4]Yagi A, Kanbara T, Morinobu N: Inhibition of mushroom-tyrosinase by aloe extract. Planta Med 1987, 53:515-517.
  • [5]Yu BP, Lee KY: Identification of potent antioxidant from Aloe barbadensis. U.S. Patent No. 5, 939, 395
  • [6]Ajabnoor MA: Effect of aloes on blood glucose levels in normal and alloxan diabetic mice. J Ethnopharmacol 1990, 28:215-220.
  • [7]Ghannam N, Kingston M, Al-Meshaal IA, Tariq M, Parman NS, Woodhouse N: The antidiabetic activity of aloes: preliminary clinical and experimental observations. Horm Res 1986, 24:288-294.
  • [8]Jones K, Hughes J, Hong M, Jia Q, Orndorff S: Modulation of melanogenesis by aloesin: a competitive inhibitor of tyrosinase. Pigment Cell Res 2002, 15:335-340.
  • [9]Lee KY, Park JH, Chung MH, Park YI, Kim KW, Lee YJ, Lee SK: Aloesin up-regulates cyclin E/CDK2 kinase activity via inducing the protein levels of cyclin E, CDK2, and CDC25A in SK-HEP-1 cells. Biochem Mol Biol Int 1997, 41:285-292.
  • [10]Hutter JA, Salman M, Stavinoha WB, Satsangi N, Williams RF, Streeper RT, Weintraub ST: Antiinflammatory C-glucosyl chromone from Aloe barbadensis. J Nat Prod 1996, 59:541-543.
  • [11]Lee KY, Weintraub ST, Yu BP: Isolation and identification of a phenolic antioxidant from Aloe barbadensis. Free Radic Biol Med 2000, 28:261-265.
  • [12]Adeyi AO, Idowu BA, Mafiana CF, Oluwalana SA, Ajayi OL, Akinloye OA: Rat model of food-induced non-obese-type 2 diabetes mellitus: comparative pathophysiology and histopathology. Int J Physiol Pathophysiol Pharmacol 2012, 4:51-58.
  • [13]Xu Z, Wang X, Zhou M, Ma L, Deng Y, Zhang H, Zhao A, Zhang Y, Jia W: The antidiabetic activity of total lignan from Fructus Arctii against alloxan-induced diabetes in mice and rats. Phytother Res 2008, 22:97-101.
  • [14]Attele AS, Zhou YP, Xie JT, Wu JA, Zhang L, Dey L, Pugh W, Rue PA, Polonsky KS, Yuan CS: Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component. Diabetes 2002, 51:1851-1858.
  • [15]Harach T, Aprikian O, Monnard I, Moulin J, Membrez M, Beolor JC, Raab T, Mace K, Darimont C: Rosemary (Rosmarinus officinalis L.) leaf extract limits weight gain and liver steatosis in mice fed a high-fat diet. Planta Med 2010, 76:566-571.
  • [16]Rajasekaran S, Sivagnanam K, Subramanian S: Antioxidant effect of Aloe vera gel extract in streptozotocin-induced diabetes in rats. Pharmacol Rep 2005, 57:90-96.
  • [17]Rajasekaran S, Ravi K, Sivagnanam K, Subramanian S: Beneficial effects of aloe vera leaf gel extract on lipid profile status in rats with streptozotocin diabetes. Clin Exp Pharmacol Physiol 2006, 33:232-237.
  • [18]al-Awadi F, Fatania H, Shamte U: The effect of a plants mixture extract on liver gluconeogenesis in streptozotocin induced diabetic rats. Diabetes Res 1991, 18:163-168.
  • [19]Rajasekaran S, Sivagnanam K, Subramanian S: Modulatory effects of Aloe vera leaf gel extract on oxidative stress in rats treated with streptozotocin. J Pharm Pharmacol 2005, 57:241-246.
  • [20]Parihar MS, Chaudhary M, Shetty R, Hemnani T: Susceptibility of hippocampus and cerebral cortex to oxidative damage in streptozotocin treated mice: prevention by extracts of Withania somnifera and Aloe vera. J Clin Neurosci 2004, 11:397-402.
  • [21]Bolkent S, Akev N, Ozsoy N, Sengezer-Inceli M, Can A, Alper O, Yanardag R: Effect of Aloe vera (L.) Burm. fil. leaf gel and pulp extracts on kidney in type-II diabetic rat models. Indian J Exp Biol 2004, 42:48-52.
  • [22]Can A, Akev N, Ozsoy N, Bolkent S, Arda BP, Yanardag R, Okyar A: Effect of Aloe vera leaf gel and pulp extracts on the liver in type-II diabetic rat models. Biol Pharm Bull 2004, 27:694-698.
  • [23]Kim K, Kim H, Kwon J, Lee S, Kong H, Im SA, Lee YH, Lee YR, Oh ST, Jo TH, Park YI, Lee CK, Kim K: Hypoglycemic and hypolipidemic effects of processed Aloe vera gel in a mouse model of non-insulin-dependent diabetes mellitus. Phytomedicine 2009, 16:856-863.
  • [24]Yimam M, Zhao J, Corneliusen B, Pantier M, Brownell LA, Jia Q: UP780, a chromone-enriched aloe composition improves insulin sensitivity. Metab Syndr Relat Disord 2013, 11:267-275.
  • [25]Tanaka M, Misawa E, Ito Y, Habara N, Nomaguchi K, Yamada M, Toida T, Hayasawa H, Takase M, Inagaki M, Higuchi R: Identification of five phytosterols from Aloe vera gel as anti-diabetic compounds. Biol Pharm Bull 2006, 29:1418-1422.
  • [26]Agarwal OP: Prevention of atheromatous heart disease. Angiology 1985, 36:485-492.
  • [27]Yongchaiyudha S, Rungpitarangsi V, Bunyapraphatsara N, Chokechaijaroenporn O: Antidiabetic activity of Aloe vera L. juice. I. Clinical trial in new cases of diabetes mellitus. Phytomedicine 1996, 3:241-243.
  • [28]Bunyapraphatsara N, Yongchaiyudha S, Rungpitarangsi V, Chokechaijaroenporn O: Antidiabetic activity of Aloe vera L. juice II. Clinical trial in diabetes mellitus patients in combination with glibenclamide. Phytomedicine 1996, 3:245-248.
  • [29]Nasiff HA, Fajardo FR, Velez F: Effect of aloe on hyperlipidemia in patients with negative response to diet. Revista Cubana Med Gen Integral 1993, 9:43-51.
  • [30]Devaraj S, Yimam M, Brownell LA, Jialal I, Singh S, Jia Q: Effects of Aloe vera supplementation in subjects with prediabetes/metabolic syndrome. Metab Syndr Relat Disord 2013, 11:35-40.
  • [31]Huseini HF, Kianbakht S, Hajiaghaee R, Dabaghian FH: Anti-hyperglycemic and anti-hypercholesterolemic effects of Aloe vera leaf gel in hyperlipidemic type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial. Planta Med 2012, 78:311-316.
  • [32]Chung CH, Hao E, Piran R, Keinan E, Levine F: Pancreatic beta-cell neogenesis by direct conversion from mature alpha-cells. Stem Cells 2010, 28:1630-1638.
  • [33]Okyar A, Can A, Akev N, Baktir G, Sutlupinar N: Effect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models. Phytother Res 2001, 15:157-161.
  • [34]Patanè G, Piro S, Anello M, Rabuazzo AM, Vigneri R, Purrello F: Exposure to glibenclamide increases rat beta cells sensitivity to glucose. Br J Pharmacol 2000, 129:887-892.
  • [35]Beppu H, Koike T, Shimpo K, Chihara T, Hoshino M, Ida C, Kuzuya H: Radical-scavenging effects of Aloe arborescens Miller on prevention of pancreatic islet B-cell destruction in rats. J Ethnopharmacol 2003, 89:37-45.
  • [36]Jain N, Vijayaraghavan R, Pant SC, Lomash V, Ali M: Aloe vera gel alleviates cardiotoxicity in streptozocin-induced diabetes in rats. J Pharm Pharmacol 2010, 62:115-123.
  • [37]Lenzen S: The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 2008, 51:216-226.
  文献评价指标  
  下载次数:43次 浏览次数:19次