期刊论文详细信息
Diabetology & Metabolic Syndrome
Alleviating effects of morin against experimentally-induced diabetic osteopenia
Mohammed M Ahmed1  Mihir Y Parmar2  Khaled A Al-Hosaini2  Salim S Al-Rejaie2  Hatem M Abuohashish1 
[1] Experimental Animal Care Center, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia;Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia
关键词: Micro CT;    Inflammation;    Oxidative stress;    Morin;    Diabetic osteopenia;   
Others  :  814729
DOI  :  10.1186/1758-5996-5-5
 received in 2012-11-13, accepted in 2013-01-21,  发布年份 2013
PDF
【 摘 要 】

Background

Plant flavonoids are emerging as potent therapeutic drugs effective against a wide range of aging diseases particularly bone metabolic disorders. Morin (3,5,7,20,40-pentahydroxyflavone), a member of flavonols, is an important bioactive compound by interacting with nucleic acids, enzymes and protein. The present study was designed to investigate the putative beneficial effect of morin on diabetic osteopenia in rats.

Methods

Streptozotocin (STZ)-induced diabetic model was used by considering 300 mg/dl fasting glucose level as diabetic. Morin (15 and 30 mg/kg) was treated for five consecutive weeks to diabetic rats. Serum levels of glucose, insulin, deoxypyridinoline cross links (DPD), osteocalcin (OC), bone specific alkaline phosphatase (BALP), telopeptides of collagen type I (CTX), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), thiobarbituric acid reactive substance (TBARS) and reduced glutathione (GSH) were estimated. Femoral bones were taken for micro CT scan to measure trabecular bone mineral density (BMD) and other morphometric parameters.

Results

Significant bone loss was documented as the level of bone turnover parameters including DPD, OC, BALP and CTX were increased in serum of diabetic rats. Morin treatment significantly attenuated these elevated levels. Bone micro-CT scan of diabetic rats showed a significant impairment in trabecular bone microarchitecture, density and other morphometric parameters. These impairments were significantly ameliorated by morin administration. Serum levels of glucose, TBARS, IL-1β, IL-6 and TNF-α were significantly elevated, while the level of insulin and GSH was decreased in diabetic rats. These serum changes in diabetic rats were bring back to normal values after 5 weeks morin treatment.

Conclusion

These findings revealed the protective effect of morin against diabetic induced osteopenia. We believed that this effect is through its both the anti-inflammatory and antioxidant properties.

【 授权许可】

   
2013 Abuohashish et al; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140710044249267.pdf 572KB PDF download
Figure 5. 23KB Image download
Figure 4. 19KB Image download
Figure 3. 36KB Image download
Figure 2. 58KB Image download
Figure 1. 21KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】
  • [1]Rakel A, Sheehy O, Rahme E, LeLorier J: Osteoporosis among patients with type 1 and type 2 diabetes. Diabetes Metab 2008, 34:193-205.
  • [2]Hamada Y, Fujii H, Fukagawa M: Role of oxidative stress in diabetic bone disorder. Bone 2009, 45(Suppl 1):S35-S38.
  • [3]Liang W, Luo Z, Ge S, Li M, Du J, Yang M, Yan M, Ye Z: Oral administration of quercetin inhibits bone loss in rat model of diabetic osteopenia. Eur J Pharmacol 2011, 670:317-324.
  • [4]King GL, Loeken MR: Hyperglycemia-induced oxidative stress in diabetic complications. Histochem Cell Biol 2004, 122:333-338.
  • [5]Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM, Luo SQ: Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB. Biochem Biophys Res Commun 2004, 314:197-207.
  • [6]Zhen D, Chen Y, Tang X: Metformin reverses the deleterious effects of high glucose on osteoblast function. J Diabetes Complications 2010, 24:334-344.
  • [7]Blakytny R, Spraul M, Jude EB: Review: the diabetic bone: a cellular and molecular perspective. Int J Low Extrem Wounds 2011, 10:16-32.
  • [8]Kapoor R, Kakkar P: Protective role of morin, a flavonoid, against high glucose induced oxidative stress mediated apoptosis in primary Rat hepatocytes. PLoS One 2012, 7:e41663.
  • [9]Sreedharan V, Venkatachalam KK, Namasivayam N: Effect of morin on tissue lipid peroxidation and antioxidant status in 1, 2-dimethylhydrazine induced experimental colon carcinogenesis. Invest New Drugs 2009, 27:21-30.
  • [10]Nandhakumar R, Salini K, Niranjali Devaraj S: Morin augments anticarcinogenic and antiproliferative efficacy against 7,12-dimethylbenz(a)-anthracene induced experimental mammary carcinogenesis. Mol Cell Biochem 2012, 364:79-92.
  • [11]Prahalathan P, Kumar S, Raja B: Morin attenuates blood pressure and oxidative stress in deoxycorticosterone acetate-salt hypertensive rats: a biochemical and histopathological evaluation. Metabolism 2012, 61:1087-1099.
  • [12]Merwid-Lad A, Trocha M, Chlebda E, Sozanski T, Magdalan J, Ksiadzyna D, Kopacz M, Kuzniar A, Nowak D, Piesniewska M, et al.: Effects of morin-5'-sulfonic acid sodium salt (NaMSA) on cyclophosphamide-induced changes in oxido-redox state in rat liver and kidney. Hum Exp Toxicol 2012, 31:812-819.
  • [13]Fang SH, Hou YC, Chang WC, Hsiu SL, Chao PD, Chiang BL: Morin sulfates/glucuronides exert anti-inflammatory activity on activated macrophages and decreased the incidence of septic shock. Life Sci 2003, 74:743-756.
  • [14]Kawabata K, Tanaka T, Honjo S, Kakumoto M, Hara A, Makita H, Tatematsu N, Ushida J, Tsuda H, Mori H: Chemopreventive effect of dietary flavonoid morin on chemically induced rat tongue carcinogenesis. Int J Cancer 1999, 83:381-386.
  • [15]Kuo HM, Chang LS, Lin YL, Lu HF, Yang JS, Lee JH, Chung JG: Morin inhibits the growth of human leukemia HL-60 cells via cell cycle arrest and induction of apoptosis through mitochondria dependent pathway. Anticancer Res 2007, 27:395-405.
  • [16]Iwase Y, Takemura Y, Ju-ichi M, Mukainaka T, Ichiishi E, Ito C, Furukawa H, Yano M, Tokuda H, Nishino H: Inhibitory effect of flavonoid derivatives on epstein-barr virus activation and two-stage carcinogenesis of skin tumors. Cancer Lett 2001, 173:105-109.
  • [17]Kitagawa S, Sakamoto H, Tano H: Inhibitory effects of flavonoids on free radical-induced hemolysis and their oxidative effects on hemoglobin. Chem Pharm Bull (Tokyo) 2004, 52:999-1001.
  • [18]Subash S, Subramanian P: Effect of morin on the levels of circulatory liver markers and redox status in experimental chronic hyperammonaemic rats. Singapore Med J 2008, 49:650-655.
  • [19]Subash S, Subramanian P: Morin a flavonoid exerts antioxidant potential in chronic hyperammonemic rats: a biochemical and histopathological study. Mol Cell Biochem 2009, 327:153-161.
  • [20]Yugarani T, Tan BK, Teh M, Das NP: Effects of polyphenolic natural products on the lipid profiles of rats fed high fat diets. Lipids 1992, 27:181-186.
  • [21]Pogula BK, Maharajan MK, Oddepalli DR, Boini L, Arella M, Sabarimuthu DQ: Morin protects heart from beta-adrenergic-stimulated myocardial infarction: an electrocardiographic, biochemical, and histological study in rats. J Physiol Biochem 2012, 68:433-446.
  • [22]Sedlak J, Lindsay RH: Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem 1968, 25:192-205.
  • [23]Salmon P: Method for ex-vivo micro-CT analysis of rat bone (proximal tibia, distal femur). Skyscan 2011. [http://www.skyscan.be/company/UM2011/abstract_38.pdf webcite]
  • [24]Lenzen S: The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 2008, 51:216-226.
  • [25]Suzuki K, Miyakoshi N, Tsuchida T, Kasukawa Y, Sato K, Itoi E: Effects of combined treatment of insulin and human parathyroid hormone(1–34) on cancellous bone mass and structure in streptozotocin-induced diabetic rats. Bone 2003, 33:108-114.
  • [26]Crozier A, Jaganath IB, Clifford MN: Dietary phenolics: chemistry, bioavailability and effects on health. Nat Prod Rep 2009, 26:1001-1043.
  • [27]Dembinska-Kiec A, Mykkanen O, Kiec-Wilk B, Mykkanen H: Antioxidant phytochemicals against type 2 diabetes. Br J Nutr 2008, 99(E Suppl 1):ES109-ES117.
  • [28]Coskun O, Kanter M, Korkmaz A, Oter S: Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and beta-cell damage in rat pancreas. Pharmacol Res 2005, 51:117-123.
  • [29]Kapoor R, Srivastava S, Kakkar P: Bacopa monnieri modulates antioxidant responses in brain and kidney of diabetic rats. Environ Toxicol Pharmacol 2009, 27:62-69.
  • [30]Thrailkill KM, Liu L, Wahl EC, Bunn RC, Perrien DS, Cockrell GE, Skinner RA, Hogue WR, Carver AA, Fowlkes JL, et al.: Bone formation is impaired in a model of type 1 diabetes. Diabetes 2005, 54:2875-2881.
  • [31]Badescu L, Badulescu O, Badescu M, Ciocoiu M: Mechanism by sambucus nigra extract improves bone mineral density in experimental diabetes. Evid Based Complement Alternat Med 2012, 2012:848269.
  • [32]Tsirella E, Mavrakanas T, Rager O, Tsartsalis S, Kallaras K, Kokkas B, Mironidou-Tzouveleki M: Low dose pioglitazone does not affect bone formation and resorption markers or bone mineral density in streptozocin-induced diabetic rats. J Physiol Pharmacol 2012, 63:201-204.
  • [33]Wauquier F, Leotoing L, Coxam V, Guicheux J, Wittrant Y: Oxidative stress in bone remodelling and disease. Trends Mol Med 2009, 15:468-477.
  • [34]Das J, Sil PC: Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress-related signaling pathways and apoptosis in rats. Amino Acids 2012, 43:1509-1523.
  • [35]Bell DS, Allbright E: The multifaceted associations of hepatobiliary disease and diabetes. Endocr Pract 2007, 13:300-312.
  • [36]Sayed AA: Ferulsinaic acid modulates SOD, GSH, and antioxidant enzymes in diabetic kidney. Evid Based Complement Alternat Med 2012, 2012:580104.
  • [37]Chang CC, Chang CY, Huang JP, Hung LM: Effect of resveratrol on oxidative and inflammatory stress in liver and spleen of streptozotocin-induced type 1 diabetic rats. Chin J Physiol 2012, 55:192-201.
  • [38]Udagawa N, Kotake S, Kamatani N, Takahashi N, Suda T: The molecular mechanism of osteoclastogenesis in rheumatoid arthritis. Arthritis Res 2002, 4:281-289. BioMed Central Full Text
  • [39]Polzer K, Joosten L, Gasser J, Distler JH, Ruiz G, Baum W, Redlich K, Bobacz K, Smolen JS, van den Berg W, et al.: Interleukin-1 is essential for systemic inflammatory bone loss. Ann Rheum Dis 2010, 69:284-290.
  • [40]Smith C, Halliwell B, Aruoma OI: Protection by albumin against the pro-oxidant actions of phenolic dietary components. Food Chem Toxicol 1992, 30:483-489.
  • [41]Mora A, Paya M, Rios JL, Alcaraz MJ: Structure-activity relationships of polymethoxyflavones and other flavonoids as inhibitors of non-enzymic lipid peroxidation. Biochem Pharmacol 1990, 40:793-797.
  • [42]Wu TW, Fung KP, Yang CC, Weisel RD: Antioxidation of human low density lipoprotein by Morin hydrate. Life Sci 1995, 57:PL51-56.
  • [43]Wu TW, Zeng LH, Wu J, Fung KP: Morin hydrate is a plant-derived and antioxidant-based hepatoprotector. Life Sci 1993, 53:PL213-218.
  • [44]Middleton E Jr, Kandaswami C, Theoharides TC: The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000, 52:673-751.
  • [45]Devipriya S, Shyamaladevi CS: Protective effect of quercetin in cisplastin- induced cell injury in the rat kidney. Ind J Pharmacol 1999, 31:422-426.
  • [46]Nettleton JA, Harnack LJ, Scrafford CG, Mink PJ, Barraj LM, Jacobs DR Jr: Dietary flavonoids and flavonoid-rich foods are not associated with risk of type 2 diabetes in postmenopausal women. J Nutr 2006, 136:3039-3045.
  • [47]Bosetti C, Bravi F, Talamini R, Parpinel M, Gnagnarella P, Negri E, Montella M, Lagiou P, Franceschi S, La Vecchia C: Flavonoids and prostate cancer risk: a study in italy. Nutr Cancer 2006, 56:123-127.
  • [48]Hara A, Sasazuki S, Inoue M, Iwasaki M, Shimazu T, Sawada N, Yamaji T, Tsugane S: Isoflavone intake and risk of gastric cancer: a population-based prospective cohort study in japan. Am J Clin Nutr 2012, 95:147-154.
  • [49]Pohaci C, Groza M, Mares L, Ciocoiu M, Badescu M: Beneficial dexa-related effects of natural polyphenols on experimentally-induced diabetes mellitus complications. Rev Med Chir Soc Med Nat Iasi 2009, 113:838-844.
  • [50]Kok LD, Wong YP, Wu TW, Chan HC, Kwok TT, Fung KP: Morin hydrate: a potential antioxidant in minimizing the free-radicals-mediated damage to cardiovascular cells by anti-tumor drugs. Life Sci 2000, 67:91-99.
  • [51]Zhang R, Kang KA, Kang SS, Park JW, Hyun JW: Morin (2',3,4',5,7-pentahydroxyflavone) protected cells against gamma-radiation-induced oxidative stress. Basic Clin Pharmacol Toxicol 2011, 108:63-72.
  • [52]Galvez J, Coelho G, Crespo ME, Cruz T, Rodriguez-Cabezas ME, Concha A, Gonzalez M, Zarzuelo A: Intestinal anti-inflammatory activity of morin on chronic experimental colitis in the rat. Aliment Pharmacol Ther 2001, 15:2027-2039.
  • [53]Kim JW, Lee JH, Hwang BY, Mun SH, Ko NY, Kim do K, Kim B, Kim HS, Kim YM, Choi WS: Morin inhibits Fyn kinase in mast cells and IgE-mediated type I hypersensitivity response in vivo. Biochem Pharmacol 2009, 77:1506-1512.
  • [54]Harasstani OA, Moin S, Tham CL, Liew CY, Ismail N, Rajajendram R, Harith HH, Zakaria ZA, Mohamad AS, Sulaiman MR, Israf DA: Flavonoid combinations cause synergistic inhibition of proinflammatory mediator secretion from lipopolysaccharide-induced RAW 264.7 Cells. Inflamm Res 2010, 59:711-721.
  • [55]Ocete MA, Galvez J, Crespo ME, Cruz T, Gonzalez M, Torres MI, Zarzuelo A: Effects of morin on an experimental model of acute colitis in rats. Pharmacology 1998, 57:261-270.
  • [56]Chen WP, Wang YL, Tang JL, Hu PF, Bao JP, Wu LD: Morin inhibits interleukin-1beta-induced nitric oxide and prostaglandin E2 production in human chondrocytes. Int Immunopharmacol 2012, 12:447-452.
  文献评价指标  
  下载次数:0次 浏览次数:7次