Türkiye’de Yayılış Gösteren Kan Şekerini Etkileyen Bitkiler Özet

Dünyada kan şekerini etkileyen bitkilerin sayısı 375’ten fazladır. Ülkemizde ise bitkilerin 69’i çeşitli bölgelerde yayılış göstermektedir. Bu bitkilerin yayılış gösterdiği bölgelere yapılacak arazi çalışmalarıyla toplanması, kültüre alınması ve fitokimyasal içeriklerinin belirlenerek kan şekeri üzerine etkilerininde araştırılması önemlidir. Önemli olduğu düşünülen bitkilerin çoğunda fitokimyasal çalışmalar yapılmış olmasına rağmen, farmakolojik çalışmalara bitki ekstraktları kullanılarak etkileri kanıtlanan önemli bitkilerin çoğunda biyoaktivitesi bilinen etken maddelerin izolasyonu gerçekleştirilmemiştir. Bu bitkilerden bazıları Coriandrum sativum, Cyamopsis tetragonoloba, Lepidium sativum, Olea europaea’dır (16). Bunun nedeni birçok durumda fitokimyasal çalışmaların farmakolojik çalışmalarla birlikte yapılmamasından kaynaklanmaktadır. bitkilerin neredeyse tamamının birçok farmakolojik etkiye de sahip oldukları bilinmektedir. Bu bitkilerde yapılan fitokimyasal çalışmalar dışında, fitoterapötik veya fitofarmakolojik çalışmaların da yapılması ve kan şekerine etkilerinin yanı sıra etken madde izolasyonlarının da yapılması gereklidir.

Sonuç

Kan şekerini etkileyen bitkilerde fitokimyasallar incelendiğinde, bileşiklerin bir kısmının birçok bitki içerisinde meydana geldiği görülmektedir. Örnek olarak bu bileşikler kersetin, ursolik asit, ferulik asit, β-sitosterol, oleanolik asit, klorojenik asit, α- ve β-amirin ve mirisetin içerir. Diğer ilgi çekici nokta, bu bileşiklerin çoğunun birden fazla farmakolojik aktiviteye ve hedef moleküle sahip olmalarıdır.

Ekstraktlar ve aktif fraksiyonlar dahil bitki kısımlarının ham preparasyonları muhtemelen çeşitli biyolojik aktiviteleri olan molekülleri içerebilir. Aynı zamanda hazırlanan preparasyonlarda kan şekerini etkileyen moleküllerin olması da mümkündür. Kafein ile insulin değişimi etkisi muhtemelen epinefrin salınımının artmasına bağlı olarak depolanan şekerin azaldığını ifade etmektedir (22). Diterpenlerin, özellikle kahvede bulunan kafestol ve kahveolün serum total kolesterol düzeylerini artırdığı ve Norveç'li kahve içicilerde yüksek koroner kalp hastalığı oranlarıyla ilişkili olduğu bildirilmiştir (23). Kahvede çok miktarda bulunan klorojenik asit, önemli bir bileşik olarak kabul edilir. Ham özütlerde olduğu gibi bir bileşik karışımı kullanıldığında, sinerjik, aditif, inhibe edici veya uyarıcı etkileri de ortaya çıkabilir.

Kan şekerinin fizyolojik olarak belli sınırlarda tutulmasını sağlayan mekanizmalar dışardan vücuda alınan besinler ve bitkilerle etkilenebilir. Karmaşık bir metabolik hastalık olan diyabette beklendiği gibi terapötik ajanlar için birçok moleküler hedef vardır. Çeşitli kimyasal sınıflara ait fitokimyasalların in vitro ve in vivo çalışmalarda kan şekeri üzerine etkileri ortaya konmuştur. Yaklaşık 300’den fazla fitokimyasal bileşik tablo 1’de gösterilmiştir. Ancak etken maddelerin varlığının yanı sıra metabolik etkilerin de tespit edilmesi gereklidir. Her koşulda bu bileşiklerin aktif farmasötik prensiplerinin ve özelliklerinin belirlenmesi önemlidir.

Kaynaklar

1. 
   Zimmet P, Alberti KGMM, Shaw J. Global and societal implications of the diabetes epidemic. Nature 2001; 414: 782–787.
   
2. 
   Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Research and Clinical Practice 2010; 87: 4–14.
   
3. 
   Chehade J, Mooradian A. A rational approach to drug therapy of type2 diabetes mellitus. Drugs 2000; 60: 95–113.
   
4. 
   Sheehan MT. Current therapeutic options in type2 diabetes mellitus: a practical approach. Clinical Medicine and Research 2003; 1: 189–200.
   
5. 
   Moller DE. New drug targets for type2 diabetes and the metabolic syndrome. Nature 2001; 414:821–827.
   
6. 
   Rotenstein LS, Kozak BM, Shivers JP, Yarchoan M, Close J, Close KL. The ideal diabetes therapy: what will it look like? How close are we? Clinical Diabetes, 2012; 30: 44-53.
   
7. 
   IDF. 2012. International Diabetes Federation Diabetes Atlas, update 2012. 6th ed. Brussels, Belgium. http:// www.idf.org/diabetesatlas/5e/update2012.
   
8. 
   Yang W, Lu J, Weng J. Prevalence of diabetes among men and women in China. N. Engl. J. Med. 2010; 362: 1090-1101.
   
9. 
   IDF 2011. International Diabetes Federation Diabetes Atlas. 5th ed. Brussels, Belgium: International Diabetes Federation Bulletin.
   
10. 
    Powers AC. Diabetes mellitus. In: Principles of Harrison’s InternalMedicine. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J. (Eds). Vol. 2, 17th Edition. New York: McGraw Hill 2008; 2275-2304.
    
11. 
    Mansour AA, Al-Maliky AA, Kasem B, Jabar A, Mosbeh KA. Prevalence of diagnosed and undiagnosed diabetes mellitus in adults aged 19 years and older in Basrah, Iraq. Diabetes Metab. Syndr. Obes. Targets Ther. 2014: 139-144.
    
12. 
    Satman I, Ömer B, Tütüncü Y, Kalaca S, Gedik S, Dinççağ N, Karşıdağ K, Genç S, Telci A, Canbaz B, Türker F, Yılmaz T, Çakır B, Tuomilehto J. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults. European Journal of Epidemiology 2013; 28 (2): 169-180.
    
13. 
    İnce M. Diyabet Hastalarının Beslenmesinde Besin Destek Ögesi Olarak Kullanılan Bitki ve Baharatlar, Yüksek Lisans Tezi, Afyon Kocatepe Ünv. Fen Bilimleri Ens. Gıda Mühendisliği Anabilim Dalı, Afyon 2010; 165 sayfa.
    
14. 
    Aslan M, Orhan N. Diyabet Tedavisinde Kullanılan Bitkisel Ürünler ve Gıda Destekleri. Mised 2010; 23: 24: 27-38
    
15. 
    WHO Expert Committee on Diabetes Mellitus, Second Report. Technical Report Series 646. WHO, Geneva 1980, p: 61
    
16. 
    Subramoniam, A. 2017. Plants with Anti-Diabetes Mellitus Properties. Boca Raton, FL: CRC Press, Taylor & Francis.
    
17. 
    McCune LM, Owen P, Johns T. Flavonoids, xanthones and other anti-oxidant polyphenols. In: Traditional Medicines for Modern Times: Antidiabetic Plants. Soumyanath, A. (Ed). Boca Raton, FL: CRC Press, Taylor & Francis 2005; 293-303.
    
18. 
    Nazaruk J, Borzym-Kluczyk M. The role of triterpenes in the management of diabetes mellitus and its complications. Phytochem. Rev. 2015; 14: 675-690.
    
19. 
    Judd PA, Ellis PR. Plant polysaccharides in the prevention and treatment of diabetes mellitus. In: Traditional Medicines for Modern Times: Antidiabetic Plants. Soumyanath, A. (Ed). Boca Raton, FL: CRC Press, Taylor & Francis, 2005; 293-303.
    
20. 
    Tübives. Turkish Plants Data Service, http://www.tubives.com, 2017.
    
21. 
    Fai YM, Tao CC. A review of oleanoic acid in natural products. Nat. Prod. Med. 2009; 28: 277-290.
    
22. 
    Gomes, JAD, Faria BG, Silva VD, Zangeronimo MG, Miranda JR, De Lima AR. Influence of integral and decaffeinated coffee brews on metabolic parameters of rats fed with hiperlip- idemic diets. Braz. Arch. Biol. Technol. 2013; 56: 829-836.
    
23. 
    Bisht S, Sisodia SS. Coffea arabica: A wonder gift to medical science. J. Nat. Pharm. 2010; 1: 58-65.
    
24. 
    Ajikumaran NS, Subramoniam A. Indian medicinal plants with anti-diabetes properties. In: Modern and Alternative Medicine for Diabetes, Khan IA, Khanum A, Khan AH. (Eds). Hydrabad, India: Ukaaz Publications 2005; 43-193.
    
25. 
    Ajikumaran NS, Sabulal B, Radhika S, Arunkumar R, Subramoniam A. Promising anti-diabetes mellitus activity of β-amyrin palmitate isolated from Hemidesmus indicus roots. Eur. J. Pharmacol. 2014; 734: 77-82.
    
26. 
    Alarcon-Aguilar FJ, Valdes-Arzata A, Xolalpa-Molina S, Banderas-Dorantes T, Jimenez-Estrada M, Hernandez-Galicia E. Hypoglycemic activity of two polysaccharides isolated from Opuntia ficus-indica and O. streptacantha. Proc. West. Pharmacol. Soc. 2003; 46: 139-142.
    
27. 
    Al-Khateeb E, Hamadi SA, Al-Hakeemi AAN, Abu-Taha M, Al-Rawi N. Hypoglycemic effect of trigonelline isolated from Iraqi fenugreek seeds in normal and alloxan-diabetic rabbits. Eur. Sci. J. 2012; 8: 16-24.
    
28. 
    Al-Snafi, AE. The pharmaceutical importance of Althaea officinalis and Althaea rosea: A review. Int. J. PharmTech. Res. 2013; 5: 1378-1385.
    
29. 
    Anderson RA, Polansky MM. Tea enhances insulin activity. J. Agric. Food Chem. 2002; 50: 7182-7186.
    
30. 
    Aruna A, Vijayalakshmi K, Karthikeyan V. Anti-diabetic screening of methanolic extract of Citrullus lanatus leaves. Am. J. PharmTech Res. 2014; 4: 295-323.
    
31. 
    Awad NE, Seida AA, Shaffie ZEN, El-Aziz, AMA. Hypoglycemic activity of Artemisia herba-alba (Asso.) used in Egyptian traditional medicine as hypoglycemic remedy. J. Appl. Pharm. Sci. 2012; 2: 30-39.
    
32. 
    Bhat MZA, Ali M, Mir SR. Anti-diabetic activity of Ficus carica L. stem barks and isolation of two new flavonol esters from the plant by using spectroscopical techniques. Asian J. Biomed. Pharm. Sci. 2013; 3: 22-28.
    
33. 
    Bhattacharya S, Rasmussen MK, Christensen LP, Young JF, Kristiansen K, Oksbjerg N. Naringenin and falcarinol stimulate glucose uptake and TBC1D1 phosphorylation in porcine myotube cultures. J. Biochem. Pharmacol. Res. 2014; 2: 91-98.
    
34. 
    Bustanji Y, Taha MO, Al-Masri IM, Mohammad MK. Docking simulations and in vitro assay unveil potent inhibitory action of papaverine against protein tyrosine phosphatase 1B. Biol. Pharm. Bull. 2009; 32: 640-645.
    
35. 
    Chang SH, Liu CJ, Kuo CH, Chen H, Lin, WY, Teng KY. Garlic oil alleviates MAPKs- and IL-6-mediated diabetes-related cardiac hypertrophy in STZ-induced DM rats. Evid. Based Complement. Altern. Med. 2011; 950150: 1-11.
    
36. 
    Chohachi, K, Yusuka S, Kajna S, Eiko M, Hiroshi S. Hypoglycemic activity of Glycan A, B, C, D and E from Saccharum officinarum. Planta Med. 1985; 51: 113-115.
    
37. 
    Çıkladilmez Ş. Diyabet Tedavisinde Kullanılan Bitkiler ve Bitkisel Ürünler, Bitirme Ödevi, Erciyes Üniversitesi Eczacılık Fakültesi. 2013, 102 Sayfa.
    
38. 
    De AU, Saha BP. Indolizines II: Search for potential oral hypoglycemic agents. J. Pharm. Sci. 1975; 64: 49-55.
    
39. 
    Devi B, Sharma N, Kumar D, Jeet K. Morus alba L. A phytopharmocological review. Int. J. Pharm. Pharmaceut. Sci. 2013; 5: 14-18.
    
40. 
    Eid HM, Haddad PS. Mechanisms of action of indigenous anti-diabetic plants from the Boreal forest of Northeastern Canada. Adv. Endocrinol. 2014; 272968: 11.
    
41. 
    El-Mostafa, K, Kharrassi YE, Badreddline A, Andreoletti P, Vamecq J, Kebbaj MSE. Nopal cactus (Opuntia ficus-indica) as a source of bioactive compounds for nutrition, health and dis- ease. Molecules 2014; 19: 14879-14881.
    
42. 
    El-Shobaki FA, El-Bahay AM, Esmail RSA, Abd-El-Megeid AA, Esmail NS. Effects of figs fruit (Ficus carica L.) and its leaves on hyperglycemia in alloxan-diabetic rats. World J. Dairy Food Sci. 2010; 5: 47-57.
    
43. 
    El-Wahab AEA, Ghareeb DA, Sarhan EE, Abu-Serie MM, Demellawy MAE. In vitro biological assessment of Berberis vulgaris and its active constituent, berberine: Antioxidants, anti- acetylcholinesterase, anti-diabetic and anticancer effects. BMC Complement. Altern. Med. 2013; 13: 218.
    
44. 
    Erdogan-Orhan I, Altun ML, Sever-Yilmaz B, Saltan G. Anti-acetylcholinesterase and anti- oxidant assets of the major components (salicin, amentoflavone, and chlorogenic acid) and the extracts of Viburnum opulus and Viburnum lantana and their total phenol and flavonoid contents. J. Med. Food 2011; 14: 434-440.
    
45. 
    Farahanikia B, Akbarzadeh T, Jahangirzadeh A, Yassa N, Shams AMR, Mirnezami T. Phytochemical investigation of Vinca minor cultivated in Iran. Iranian J. Pharm. Res. 2011; 10: 777-785.
    
46. 
    Firdous SM. Phyto-chemicals for the treatment of diabetes. EXCLIJ. 2014; 13: 451-453.
    
47. 
    Ghorbani A. Best herbs for managing diabetes: A review of clinical studies. Brazilian J. Pharm. Sci. 2013; 49: 413-418.
    
48. 
    Hozayen WGM, Bastawy M, Hamed MZ. Biochemical effects of Cichorium intybus and Sonchus oleraceus infusions and esculetin on streptozotocin-induced diabetic albino rats. J. Am. Sci. 2011; 7: 1124-1137.
    
49. 
    Hsu FL, Chen YC, Cheng JT. Caffeic acid as active principle from the fruit of Xanthium strumarium to lower plasma glucose in diabetic rats. Planta Med. 2000; 66: 228-230.
    
50. 
    Jain, V, Viswanatha GL, Manohar D, Shivaprasad HN. Isolation of antidiabetic principle from fruit rinds of Punica granatum. Evid. Based Complement. Altern. Med. 2012; 147202.
    
51. 
    Jiang CS, Liang L, Guo Y. Natural products possessing protein tyrosine phosphatase 1B (PTP1B) inhibitory activity found in the last decades. Acta Pharmacologica Sinica 2012; 33: 1217-1245.
    
52. 
    Kaithwas G, Majumdar DK. In vitro antioxidant and in vivo antidiabetic, antihyperlipidemic activity of linseed oil against streptozotocin-induced toxicity in albino rats. Eur. J. Lipid Sci. Technol. 2012; 144: 1237-1245.
    
53. 
    Karawya, MS, Abde SM, EI-Olemy MM, Farrag NM. Diphenylamine, an antihyperglycemic agent from onion and tea. J. Nat. Prod. 1984; 47: 775-780.
    
54. 
    Kavalal G, Tuncel H, Goksel S, Hatemi HH. Hypoglycemic activity of Urtica pilulifera in streptozotocin-diabetic rats. J. Ethnopharmacol. 2003; 84: 241-245.
    
55. 
    Kawabata J, Mizuhata K, Sato E, Nishioka T, Aoyama Y, Kasai T. 6-Hydroxyflavonoids as a-glucosidase inhibitors from marjoram (Origanum majorana) leaves. Biosci. Biotechnol. Biochem. 2003; 67: 445-447.
    
56. 
    Kim J, Kim CS, Lee YM, Sohn E, Jo K, Shin SD. Scopoletin inhibits rat aldose reductase activity and cataractogenesis in galactose-fed rats. Evid. Based Complement. Alternat. Med. 2013; 787138: 8.
    
57. 
    Kim KH, Kim KS, Shin MH, Jang EG, Kim EY, Lee JH. Aqueous extract of Anemarrhena asphodeloides stimulate glucagon-like peptide-1 secreation in enteroendocrine NCI- H716 cells. BioChip J. 2013; 7: 188-193.
    
58. 
    Kim TH, Kim JK, Kang YH, Lee JY, Kang IJ, Lim SS. Aldose reductase inhibitory activity of compounds from Zea mays L. Biomed. Res. Int. 2013: 727143.
    
59. 
    Konno C, Mizuno T, Hikino H. Isolation and hypoglycemic activity of Ephedrans A, B, C, D and E, glycans of Ephedra distachya herb. Planta Med. 1985; 51: 162-163.
    
60. 
    Kumar B, Gupta SK, Nag TC, Srivastava S, Saxena R. Greentea prevents hyperglycemia- induced retinal oxidative stress and inflammation in streptozotocin-induced diabetic rats. Ophthalmic Res. 2012; 47: 103-108.
    
61. 
    Kumar VR, Chauhan S. Mulberry: Life enhancer. J. Med. Plant Res. 2008; 2: 271-278.
    
62. 
    Kumari K, Augusti KT. Antidiabetic and antioxidant effects of S-methyl cysteine sulfoxide isolated from onions (Allium cepa L.) as compared to standard drugs in alloxan diabetic rats. Indian J. Exp. Biol. 2002; 40: 1005-1009.
    
63. 
    Kuroda M, Mimaki Y, Sashida Y, Mae T, Kishida H, Nishiyama H. Phenolics with PPAR- ligand binding activity obtained from licorice (Glycyrrhiza uralensis roots) and ameliorative effects of glycyrin on genetically diabetic KK-Ay mice. Bioorg. Med. Chem. Lett. 2004; 13: 4267-4272.
    
64. 
    Li HM, Kim JK, Jang JM, Kwon SO, Cui CB, Lim SS. 2012a. The inhibitory effect of Prunella vulgaris L. on aldose reductase and protein glycation. J. Biomed. Biotechnol. 2012(928159): 7.
    
65. 
    Li J, Liu T, Wang L, Guo X, Xu T, Wu L. Anti-hyperglycemic and anti-hyperlipidemic actions of Cinnamaldehyde in C57BLKS/J db/db mice. J. Tradit. Chin. Med. 2012; 32: 446-452.
    
66. 
    Li, Q, Qu H. Study on the hypoglycemic activities and metabolism of alcohol extract of Alismatis Rhizoma. Fitoterapia 2012; 83: 1046-1053.
    
67. 
    Li Y, Ding Y. Minireview: Therapeutic potential of myricetin in diabetes mellitus. Food Science Human Wellness 2012; 1: 19-25.
    
68. 
    Luo Q, Cai Y, Yan J, Sun M, Corke H. Hypohlycemic and hypolipidemic effects and antioxi- dant activity of fruit extracts from Lycium barbarum. Life Sci. 2004; 76: 137-149.
    
69. 
    McCarty MF. Potential utility of natural polyphenols for reversing fat-induced insulin resistance. Med. Hypotheses 2005; 64: 628-635.
    
70. 
    Merghache S, Zerriouh M, Merghache D, Tabti B, Djaziri R, Ghalem S. Evaluation of hypoglycaemic and hypolipidemic activities of Globularin isolated from Globularia alypum L. in normal and streptozotocin-induced diabetic rats. J. Appl. Pharm. Sci. 2013; 3: 1-7.
    
71. 
    Middha SK, Usha T, Pande V. A review on anti-hyperglycemic and hepatoprotective activity of eco-friendly Punica granatum peel waste. Evid. Based Complement. Altern. Med. 2013; (656172): 10.
    
72. 
    Miura T, Nosaka K, Ishii H, Ishida T. Antidiabetic effect of Nitobegiku, the herb Tithonia diversifolia, in KK-Ay diabetic mice. Biol. Pharm. Bull. 2005; 28: 2152-2154.
    
73. 
    Mohamed AEH, El-Sayed MA, Hegazy ME, Helaly SE, Esmail AM, Mohamed NS. Chemical constituents and biological activities of Artemisia herba-alba. Rec. Nat. Prod. 2010; 4: 1-25.
    
74. 
    Mokhber-Dezfuli N, Saeidnia S, Gohari AR, Kurepaz-Mahmoodabadi M. Phytochemistry and pharmacology of Berberis Species. Phcog. Rev. 2014; 8: 8-15.
    
75. 
    Moloudizargari M, Mikaili P, Aghajanshakeri S, Asghari MH, Shayegh J. Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids. Pharmacogn Rev. 2013; 7: 199-212.
    
76. 
    Moorthy R, Prabhu KM, Murthy PS. Anti-hyperglycemic compound GII from fenugreek (Trigonella foenum-graceum Linn) seeds, its purification and effect in diabetes mellitus. Ind. J. Exp. Biol. 2010; 48: 1111-1118.
    
77. 
    Mueller M, Lukas B, Novak J, Simoncini T, Genazzani AR, Jungbauer A. Oregano: A source for peroxisome proliferator-activated receptor gamma antagonists. J. Agric. Food Chem. 2008; 56: 11621-11630.
    
78. 
    Paarakh PM. Coriandrum sativum Linn. - A review. Pharmacology online 2009; 3: 561-573.
    
79. 
    Paneda C, Villar AV, Alonso A, Goni FM, Varela F, Brodbeck U. Purification and charac- terization of insulin-mimetic inositol phosphoglycan-like molecules from grass pea (Lathyrus sativus) seeds. Mol. Med. 2001; 7: 454-460.
    
80. 
    Patade GR, Marita AR. Metformin: A journey from countryside to the bedside. J. Obes. Metab. Res. 2014; 1: 127-130.
    
81. 
    Potterat O. Goji (Lycium barbarum and L. chinense): Phytochemistry, pharmacology and safety in the perspective of traditional uses and recent popularity. Planta Med. 2009; 76: 7-19.
    
82. 
    Qadan F, Verspohl EJ, Nahrstedt A, Petereit F, Matalka KZ. Cinchonain Ib isolated from Eriobotrya japonica induces insulin secretion in vitro and in vivo. J. Ethnopharmacol. 2009; 124: 224-227.
    
83. 
    Sahu PK, Giri DD, Singh R, Pandey P, Gupta S, Shrivastava AK. Therapeutic and medicinal uses of Aloe vera: A review. Pharmocol. Pharm. 2013; 4: 599-610.
    
84. 
    hydroxyisoleucine: A novel amino acid potentiator of insulin secretion. Diabetes 1998; 47: 206-210.
    
85. 
    Sauvaire Y, Petit P, Broca C, Manteghetti M, Baissac Y, Fernandez-Alvarez J. 4-
    
86. 
    Sezik E, Aslan M, Yesilada E, Ito S. Hypoglycaemic activity of Gentiana olivieri and isolation of the active constituent through bioassay-directed fractionation techniques. Life Sci. 2005; 76: 1223-1238.
    
87. 
    Shah TI, Sharma E, Ahmad G. Juglans regia L. A phytopharmocological review. World J. Pharm. Sci. 2014; 2: 364-373.
    
88. 
    Sharma P, Dubey G, Kaushik S. Chemical and medico-biological profile of Cyamopsios tetragonoloba (L.) Taub: An overview. J. Appl. Pharm. Sci. 2011; 1: 32-37.
    
89. 
    Smirin P, Taler D, Abitbol G, Brutman-Barazani T, Kerem Z, Sampson SR. Sarcopoterium spinosum extract as an antidiabetic agent: In vitro and in vivo study. J. Ethanopharmacol. 2010; 129: 10-17.
    
90. 
    Song MK, Roufogalis BD, Huang TH. Reversal of the caspase-dependent apoptotic cytotoxicity pathway by taurine from Lycium barbarum (Goji Berry) in human retinal pigment epithelial cells: Potential benefit in diabetic retinopathy. Evid. Based Complement. Altern. Med. 2012; 323784.
    
91. 
    Takahashi M, Konno C, Hikino H. Isolation and hypoglycemic activity of coixans A, B, and C, glycans of Coix lachrymal-jobi var. mayuen seeds. Planta Med. 1986; 1: 64-65.
    
92. 
    Takii H, Kometani T, Nishimura T, Nakae T, Okada S, Fushiki T. Anti-diabetic effect of glycyrrhizin in genetically diabetic KK-Ay mice. Biol. Pharm. Bull. 2000; 24: 484-487.
    
93. 
    Wang A, Liu D, Luo J, Suh K, Moore W, Alkhalidy H. Phytochemical genistein promotes pancreatic beta-cell survival and exerts anti-diabetic effect via GPR30-mediated mechanism. FASEB J. 2014; 29(1): Supplement 1045.44.
    
94. 
    Wang CP, Zhang LZ, Li GC, Shi YW, Li JL, Xang XC. Mulberroside A protects against ischemic impairment in primary culture of rat cortical neurons after oxygen-glucose deprivation followed by reperfusion. J. Neurosci. Res. 2014; 92: 944-954.
    
95. 
    Wang L, Waltenberger B, Pferschy-Wenzing EM, Blunder M, Liu X, Malainer C. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): A review. Biochem. Pharmacol. 2014; 92: 73-89.
    
96. 
    Wang Z, Chen Z, Yang S, Wang Y, Huang Z, Gao J. Berberine ameliorates collagen-induced arthritis in rats associated with anti-inflammatory and anti-angiogenic effects. Inflammation 2014; 37: 1789-1798.
    
97. 
    Wargent ET, Zaibi MS, Silvestri C, Hislop DC, Stocker CJ, Stott CG. The cannabinoid A(9)-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutr. Diabetes 2013; 3: e68. doi:10.1038/nutd.2013.9.
    
98. 
    Weiss L, Zeira M, Reich S, Har-Noy M, Mechoulam R, Slavin S, Gallily R. Cannabidiol lowers incidence of diabetes in non-obese mice. Autoimmunity 2006; 39: 143-151.
    
99. 
    WHO 1999. WHO Monographs on Selected Medicinal Plants. Vol. 1. Geneva, Switzerland: WHO Press.
    
100. 
     WHO 2009. WHO Monographs on Selected Medicinal Plants. Vol. 4. Geneva, Switzerland: WHO Press.
     
101. 
     Xia X, Yan J, Shen Y, Tang K, Yin J, Zhang Y. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PLoS One 2011; 6: e16556.
     
102. 
     Xiu LM, Miura AB, Yamamoto K, Kobayashi T, Song QH, Kitamura H. Pancreatic islet regeneration by ephedrine in mice with streptozotocin-induced diabetes. Am. J. Chin. Med. 2001; 29: 493-500.
     
103. 
     Yoo NH, Jang DS, Yoo JL, Lee YM, Kim YS, Cho JH, Kim JS. Erigeroflavanone, a flavanone türevi from the flowers of Erigeron annuus with protein glycation and aldose reductase inhibitory activity. J. Nat. Prod. 2008; 71: 713-715.
     
104. 
     Yoshikawa M, Shimada H, Morikawa T, Yoshizumi S, Matsumura N, Murakami T, Matsuda H, Hori K, Yamahara J. Medicinal food stuffs. VII. On the saponin constituents with glucose and alcohol absorption-inhibitory activity from a food garnish “Tonburi” the fruit of Japanese Kochia scoparia (L.) Schrad.: Structures of scoparianosides A, B, and C. Chem. Pharmaceut. Bull. 1997; 45: 1300-1305.
     
105. 
     Zhang M, Chen M, Zhang HQ, Sun S, Xia B, Wu FH. In vivo hypoglycemic effects of phenolics from the root bark of Morus alba. Fitoterapia 2009a; 80: 475-477.
     
106. 
     Zhang H, Matsuda H, Yamashita C, Nakamura S, Yoshikawa M. Hydrangeic acid from the processed leaves of Hydrangea macrophylla var. thunbergii as a new type of anti-diabetic compound. Eur. J. Pharmacol. 2009b; 606: 255-261.
     
107. 
     Zhang J, Li L, Kim SH, Hagerman AE, Lu J. Anti-cancer, anti-diabetic and other pharmacologic and biological activities of penta-galloylglucose. Pharm. Res. 2009c; 26: 2066-2080.
     
108. 
     Zhou T, Deng X, Qiu J. Antimicrobial activity of licochalcone E against Staphylococcus aureus and its impact on the production of staphylococcal alpha-toxin. J. Microbiol. Technol. 2012; 22: 800-805.