Planta Med 2017; 83(14/15): 1141-1148
DOI: 10.1055/s-0043-107616
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Antidiabetic Activities of an LC/MS Fingerprinted Aqueous Extract of Fagonia cretica L. in Preclinical Models[*]

Imran Nazir
1   Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
5   Trinity College Dublin, School of Pharmacy & Pharmaceutical Sciences and Trinity Biosciences Institute (TBSI), Dublin, Ireland
,
Nisar ur Rahman
2   Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan
,
Zunaira Alvi
1   Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
,
M. Hafizur Rahman
3   Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, Karachi, Pakistan
,
Jandirk Sendker
4   University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany
,
Tao Zhang
5   Trinity College Dublin, School of Pharmacy & Pharmaceutical Sciences and Trinity Biosciences Institute (TBSI), Dublin, Ireland
,
Neil Frankish
5   Trinity College Dublin, School of Pharmacy & Pharmaceutical Sciences and Trinity Biosciences Institute (TBSI), Dublin, Ireland
,
Helen Sheridan
5   Trinity College Dublin, School of Pharmacy & Pharmaceutical Sciences and Trinity Biosciences Institute (TBSI), Dublin, Ireland
› Author Affiliations
Further Information

Publication History

received 07 February 2017
revised 15 March 2017

accepted 23 March 2017

Publication Date:
07 April 2017 (online)

Abstract

Diabetes mellitus is a chronic disease and one of the most important public health challenges facing mankind. Fagonia cretica is a medicinal plant used widely in the Punjab in Pakistan. A recent survey has demonstrated that traditional healers and herbalists frequently use this plant to treat diabetes. In the current study, the traditional medicine was prepared as a tea, and the profile of the main metabolites present in the traditional medicine was analysed via LC/MS/MS. The extract was shown to contain a number of phenolic glycosides including quercetin-3-O-rutinoside, kaempferol-3-O-rutinoside, kaempferol-3-O-glycoside, kaempferol-3(6′-malonylglucoside), isorhamnetin-3-O-rutinoside, and isorhamnetin 3-(6″-malonylglucoside) in addition to two unidentified sulphonated saponins. The traditional medicine inhibits α-glucosidase in vitro with an IC50 of 4.62 µg/mL. The hypoglycaemic effect of the traditional medicine was evaluated in normoglycaemic and streptozotocin-treated diabetic rats, using glibenclamide as an internal control. The preparation (250 or 500 mg/kg body weight) was administered once a day for 21 consecutive days. The dose of 500 mg/kg was effective in the management of the disease, causing a 45 % decrease in the plasma glucose level at the end of the experimental period. Histological analysis of pancreatic sections confirmed that streptozotocin/nictotinamide treatment caused destruction of pancreatic islet cells, while pancreatic sections from the treatment groups showed that both the extract and glibenclamide partially prevented this deterioration. The mechanism of this protective effect is unclear. However, such a finding suggests that ingestion of the tea could confer additional benefits and should be investigated further.

* Dedicated to Professor Dr. Max Wichtl in recognition of his outstanding contribution to pharmacognosy research.


Supporting Information

 
  • References

  • 1 World Health Organization. Definition and Diagnosis of Diabetes mellitus and intermediate Hyperglycaemia: Report of a WHO/IDF Consultation. Geneva, Switzerland: World Health Organization; 2006
  • 2 Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414: 813-820
  • 3 Al Quwaidhi AJA. Epidemiological modelling of Type 2 Diabetes in Saudi Arabia: predicted Trends and public Health Implications [Dissertation]. Newcastle: University of Newcastle; 2013
  • 4 Hussain M, Naqvi SBS, Khan MA, Rizvi M, Alam S, Abbas A, Akram M. Direct cost of the treatment of diabetes mellitus type 2 in Pakistan. Int J Pharm Pharm Sci 2014; 6: 261-262
  • 5 Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, Dagogo-Jack S, Davidson MB, Einhorn D, Garvey WT, Grunberger G, Handelsman Y, Hirsch IB, Jellinger PS, McGill JB, Mechanick JI, Rosenblit PD, Umpierrez GE, Davidson MH. American Association of Clinical Endocrinologistsʼ comprehensive diabetes management algorithm 2013 consensus statement. Endocr Pract 2013; 19: 536-557
  • 6 Rutten GEHM, Verhoeven S, Heine RJ, De Grauw P, Cromme K, Reenders E, Van Ballegooie E, Wiersma T. Dutch College of General Practitionersʼ guidelines on type 2 diabetes mellitus. Huisarts Wet 1999; 42: 67-84
  • 7 International Diabetes Federation. Pakistan. Available at. http://www.idf.org/membership/mena/pakistan Accessed April 5, 2017
  • 8 Campbell LK, White JR, Campbell RK. Acarbose: its role in the treatment of diabetes mellitus. Ann Pharmacother 1996; 30: 1255-1262
  • 9 Ceriello A. Postprandial hyperglycemia and diabetes complications is it time to treat?. Diabetes 2005; 54: 1-7
  • 10 Kusunoki Y, Katsuno T, Myojin M, Miyakoshi K, Ikawa T, Matsuo T, Ochi F, Tokuda M, Murai K, Miuchi M, Hamaguchi T, Miyagawa J, Namba M. Effect of additional administration of acarbose on blood glucose fluctuations and postprandial hyperglycaemia in patients with type 2 diabetes mellitus under treatment with alogliptin. Endocr J 2013; 60: 431-439
  • 11 Zhou JH, Li X, Zhang Y, Peng Y, Mo Y, Bao Y, Jia W. Nateglinide and acarbose are comparably effective reducers of postprandial glycemic excursions in Chinese antihyperglycemic agent-naive subjects with type 2 diabetes. Diabetes Technol Ther 2013; 15: 481-488
  • 12 Kalra S, Gupta Y. The insulin: glucagon ratio and the choice of glucose-lowering drugs. Diabetes Ther 2016; 7: 1-9
  • 13 Patwardhan B. Traditional medicine: modern approach for affordable healthcare. WHO Geneva, Switzerland: World Health Organization; 2005. Available at http://www.who.int/intellectualproperty/studies/B.Patwardhan2.pdf Accessed October 17, 2016
  • 14 Shaikh BT, Hatcher J. Complementary and alternative medicine in Pakistan: prospects and limitations. Evid Based Complement Alternat Med 2005; 2: 139-142
  • 15 Nazir I, ur Rahman N, Chan K, Frankish N, Sheridan H. Use of herbal plants to treat diabetes mellius in Pakistan. Ethnobotanical study of antidiabetic plants of cholistan desert, district Bahawalpur, Pakistan. London BioNat: University of East London; 2013
  • 16 Qureshi H, Asif S, Ahmed H, Al-Kahtani HA, Hayat K. Chemical composition and medicinal significance of Fagonia cretica L: a review. Nat Prod Res 2015; 30: 625-639
  • 17 Chopra RM, Handa KL, Kapur LD, Chopra IC. Indigenous Drug of India. 2nd ed.. New Delhi: Academic Press; 1982: 507
  • 18 Nadkarni KM. Dr. K.M. Nadkarniʼs Indian Materia Medica: with Ayurvedic, Unani-tibbi, Siddha, allopathic, homeopathic, naturopathic & Home Remedies, Appendices & Indexes, Volume 2. Mumbai: Popular Prakashan; 1954
  • 19 Ahmad M, Khan MA, Arshad M, Zafar M. Ethnophytotherapical approaches for the treatment of diabetes by the local inhabitants of district Attock (Pakistan). Ethnobot Leaflets 2004; 1: 7
  • 20 Ahmad M, Qureshi R, Arshad M, Khan M, Zafar M. Traditional herbal remedies used for the treatment of diabetes from the district of Attock (Pakistan). Pak J Bot 2009; 41: 2777-2782
  • 21 Razi MT, Asad MH, Khan T, Chaudhary MZ, Ansari MT, Arshad MA, Saqib QN. Antihaemorrhagic potential of Fagonia cretica L. against Naja naja karachiensis (black Pakistan cobra) venom. Nat Prod Res 2011; 25: 1902-1907
  • 22 Hussain A, Zia M, Mirza B. Cytotoxic and antitumor potential of Fagonia cretica L. Turk J Biol 2007; 31: 19-24
  • 23 Rawal AD, Nath N, Yadav S, Pande S, Meshram SU, Biswas SK. Rubia cordifolia, Fagonia cretica Linn and Tinospora cordifolia exert anti-inflammatory properties by modulating platelet aggregation and VEGF, COX-2 and VCAM gene expressions in rat hippocampal slices subjected to ischemic reperfusion injury. Int J Appl Res Nat Prod 2009; 2: 19-26
  • 24 Rawal AK, Muddeshwar MG, Biswas SK. Rubia cordifolia, Fagonia cretica L. and Tinospora cordifolia exert neuroprotection by modulating the antioxidant system in rat hippocampal slices subjected to oxygen glucose deprivation. BMC Complement Altern Med 2004; 4: 11
  • 25 Shishodia S, Majumdar S, Banerjee S, Aggarwal BB. Occurrence of taraxerol and taraxasterol in medicinal plants. Pharmacogn Rev 2015; 9: 19-23
  • 26 Sharma K, Zafar R. Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through suppression of IkappaBalpha kinase and p65 phosphorylation: correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1. Cancer Res 2003; 63: 4375-4383
  • 27 Abdel Khalik SM, Miyase T, El-Ashaal HA, Meleek FR. Triterpenoid saponins from Fagonia cretica . Phytochemistry 2000; 54: 853-859
  • 28 Anjum MI, Ahmed E, Jabbar A, Malik A, Ashraf M, Moazzam M, Rasool MA. Antimicrobial constituents from Fagonia cretica . J Chem Soc Pak 2007; 29: 634-639
  • 29 El-Negoumy SI, Wakeel SAM, El-Hadidi MN, Saleh NAM. The flavonoids of the F. arabica-complex (Zygophyllaceae). Phytochemistry 1986; 25: 2423-2424
  • 30 Lam M, Carmichael AR, Griffiths HR. An aqueous extract of Fagonia cretica induces DNA damage, cell cycle arrest and apoptosis in breast cancer cells via FOXO3a and p53 expression. PLoS One 2012; 7: e40152
  • 31 Saleem S, Jafri L, ul Haq I, Chang LC, Calderwood D, Green BD, Mirza B. Plants Fagonia cretica L. and Hedera nepalensis K contain natural compounds with potent dipeptidyl peptidase-4 (DPP-4) inhibitory activity. J Ethnopharmacol 2014; 156: 26-32
  • 32 Sheridan H, Krenn L, Jiang R, Sutherland I, Ignatova S, Marmann A, Liang X, Sendker J. The potential of metabolic fingerprinting as a tool for the modernisation of TCM preparations. J Ethnopharmacol 2012; 140: 482-491
  • 33 Sheridan H, Kopp B, Krenn L, Guo D, Sendker J. Traditional Chinese herbal medicine preparation: invoking the butterfly effect. Science 2015; 350: S64-S66
  • 34 Sendker J, Ellendorff T, Hölzenbein A. Occurrence of benzoic acid esters as putative catabolites of prunasin in senescent leaves of Prunus laurocerasus . J Nat Prod 2016; 79: 1724-1729
  • 35 Shaker KH, Bernhardt M, Elgamal MHA, Seifert K. Sulfonated triterpenoid saponins from Fagonia indica . Z Naturforsch C 2000; 55: 520-523
  • 36 Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci 2008; 4: 89-96
  • 37 Wongsa P, Chaiwarit J, Zamaludien A. In vitro screening of phenolic compounds, potential inhibition against α-amylase and α-glucosidase of culinary herbs in Thailand. Food Chem 2012; 131: 964-971
  • 38 Kalra S. Alpha glucosidase inhibitors. J Pak Med Assoc 2014; 64: 474-476
  • 39 Ma HY, Gao HY, Sun J, Huang J, Xu XM, Wu LJ. Constituents with α-glucosidase and advanced glycation end-product formation inhibitory activities from Salvia miltiorrhiza Bge. J Nat Med 2011; 65: 37-42
  • 40 Jo SH, Ka EH, Lee HS, Apostolidis HD, Jang HD, Kwon YI. Comparison of antioxidant potential and rat intestinal α-glucosidases inihibitory activities of quercetin, rutin, and isoquercetin. Int J Appl Res Nat Prod 2009; 2: 52-60
  • 41 Kamalakkannan N, Prince PSM. Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic wistar rats. Basic Clin Pharmacol Toxicol 2006; 98: 97-103
  • 42 Lee CC, Hsu WH, Shen SR, Cheng YH, Wu SC. Fagopyrum tataricum (buckwheat) improved high-glucose-induced insulin resistance in mouse hepatocytes and diabetes in fructose-rich diet-induced mice. Exp Diabetes Res 2012; 2012: 375673
  • 43 Chang CLT, Lin Y, Bartolome AP, Chen YC, Chiu SC, Yang WC. Herbal therapies for type 2 diabetes mellitus: chemistry, biology, and potential application of selected plants and compounds. Evid Based Complement Alternat Med 2013; 2013: 378657
  • 44 Rabbani SI, Devi K, Khanam S. Protective role of glibenclamide against nicotinamide-streptozotocin induced nuclear damage in diabetic Wistar rats. J Pharmacol Pharmacother 2010; 1: 18-23