Login Register Cart 0
Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Therapeutic Potential of Silybum marianum and Pergularia tomentosa Extracts from Jordanian Origin in Diabetes Mellitus

Author(s): Nuha I. Sweidan*, Reema A. Abu Khalaf, Alaa' M. Shatat and Wa'ed A. Hammad

Volume 18, Issue 8, 2022

Published on: 25 March, 2022

Article ID: e210222201293 Pages: 8

DOI: 10.2174/1573407218666220221090910

Price: $65

Abstract

Background: Jordan is a country well-known for its diversity in wild plants, and for many decades, folk medicines have represented part of its cultural heritage. In the present study, investigations have been focused on the therapeutic potential of Silybum marianum and Pergularia tomentosa on type 2 diabetes mellitus. In type 2 diabetes, which is considered a global health problem, the body cannot respond to or produce insulin hormonem, which raises the blood glucose level, resulting in mortality, morbidity, healthcare expenses, and reduced life quality. Dipeptidyl peptidase-IV (DPP-IV) enzyme, a serine protease, is responsible for deactivating incretin hormones that promote insulin secretion. Accordingly, the DPP-IV inhibitory activity of these plant extracts that prolong the hypoglycemic effect of incretins was evaluated.

Methods: The aerial parts of S. marianum and P. tomentosa were dried, ground, and extracted with ethanol. The ethanol extract was dried under reduced pressure and was partitioned by methanol, butanol, and hexane according to a systematic procedure. The inhibition of the DPP-IV enzyme by the different extracts was studied (at 10.0 mg/mL concentration). Sitagliptin was used as the positive control.

Results: Fortunately, most of the plant extracts have noticeable inhibitory activity against the DPPIV enzyme. It was found that the tested methanol extract of S. marianum has an inhibitory activity of 75.6% and the butanol extract of P. tomentosa has an inhibitory activity of 73.6%, which are analogous to DPP-IV inhibition of sitagliptin (78.5%), the used positive inhibitor. A superior inhibition of 98.1% was displayed for the butanol extract of S. marianum at 10.0 mg/ mL concentration.

Conclusion: The revealed DPP-IV inhibitory activity of tested extracts advocates that their active constituents, particularly flavonoids, are capable of binding to the enzyme’s active cleft.

Keywords: Cardenolides, diabetes mellitus, dipeptidyl peptidase-IV, flavonolignans, Pergularia tomentosa, Silybum marianum.

Graphical Abstract

[1]
Flora, K.; Hahn, M.; Rosen, H.; Benner, K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am. J. Gastroenterol., 1998, 93(2), 139-143.
[http://dx.doi.org/10.1111/j.1572-0241.1998.00139.x] [PMID: 9468229]
[2]
Urtasun, R.; Conde de la Rosa, L.; Nieto, N. Oxidative and nitrosative stress and fibrogenic response. Clin. Liver Dis., 2008, 12(4), 769-790. viii.
[http://dx.doi.org/10.1016/j.cld.2008.07.005] [PMID: 18984466]
[3]
Surai, P.F. Silymarin as a natural antioxidant: An overview of the current evidence and perspectives. Antioxidants, 2015, 4(1), 204-247.
[http://dx.doi.org/10.3390/antiox4010204] [PMID: 26785346]
[4]
Clichici, S.; Olteanu, D.; Nagy, A.L.; Oros, A.; Filip, A.; Mircea, P.A. Silymarin inhibits the progression of fibrosis in the early stages of liver injury in CCl₄-treated rats. J. Med. Food, 2015, 18(3), 290-298.
[http://dx.doi.org/10.1089/jmf.2013.0179] [PMID: 25133972]
[5]
Esmaeil, N.; Anaraki, S.B.; Gharagozloo, M.; Moayedi, B. Silymarin impacts on immune system as an immunomodulator: One key for many locks. Int. Immunopharmacol., 2017, 50, 194-201.
[http://dx.doi.org/10.1016/j.intimp.2017.06.030] [PMID: 28672215]
[6]
Andrew, R.; Izzo, A.A. Principles of pharmacological research of nutraceuticals. Br. J. Pharmacol., 2017, 174(11), 1177-1194.
[http://dx.doi.org/10.1111/bph.13779] [PMID: 28500635]
[7]
Kvasnicka, F.; Bíba, B.; Sevcík, R.; Voldrich, M.; Krátká, J. Analysis of the active components of silymarin. J. Chromatogr. A, 2003, 990(1-2), 239-245.
[http://dx.doi.org/10.1016/S0021-9673(02)01971-4] [PMID: 12685603]
[8]
Zhu, H.J.; Brinda, B.J.; Chavin, K.D.; Bernstein, H.J.; Patrick, K.S.; Markowitz, J.S. An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: A dose escalation study. Drug Metab. Dispos., 2013, 41(9), 1679-1685.
[http://dx.doi.org/10.1124/dmd.113.052423] [PMID: 23835761]
[9]
Santos, J.; Mira, L.B.; Freire, A.M.; Azevedo, M.; Manso, C. Placental aldose reductase inhibition by Silybin (preliminary communica-tion). Acta Med. Port., 1984, 5(4-5), 115-117.
[PMID: 6431756]
[10]
MacDonald-Ramos, K.; Michán, L.; Martínez-Ibarra, A.; Cerbón, M. Silymarin is an ally against insulin resistance: A review. Ann. Hepatol., 2021, 23, 100255.
[http://dx.doi.org/10.1016/j.aohep.2020.08.072] [PMID: 32950646]
[11]
Alsaid, M.S.; Hifnawy, M.S.; McPhail, A.T.; McPhail, D.R. Ghalakinoside, a cytotoxic cardiac glycoside from Pergularia tomentosa. Phytochemistry, 1988, 27(10), 3245-3250.
[http://dx.doi.org/10.1016/0031-9422(88)80035-9]
[12]
Hammiche, V.; Maiza, K. Traditional medicine in Central Sahara: Pharmacopoeia of Tassili N’ajjer. J. Ethnopharmacol., 2006, 105(3), 358-367.
[http://dx.doi.org/10.1016/j.jep.2005.11.028] [PMID: 16414225]
[13]
Hosseini, S.H.; Masullo, M.; Cerulli, A.; Martucciello, S.; Ayyari, M.; Pizza, C.; Piacente, S. Antiproliferative cardenolides from the aerial parts of pergularia tomentosa. J. Nat. Prod., 2019, 82(1), 74-79.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00630] [PMID: 30629433]
[14]
Sweidan, N.; Esawi, E.; Ismail, M.; Alshaer, W. Anticancer Cardenolides from the aerial parts of Calortopis procera. Z. Naturforsch. C J. Biosci., 2021, 76(5-6), 243-250.
[http://dx.doi.org/10.1515/znc-2020-0281] [PMID: 33770827]
[15]
Rayyan, W.A.; Alshammari, S.A.G. AL-Sammary, A.M.F.; AL-Shammari, M.S.S.; Seder, N.; Qatoosh, L.F.A.; Bostami, M.; Mansoor, K.; Hamad, M.F.; Al-Majali, I.S.; Daiyyah, W.A. The phytochemical analysis and antimicrobial activity of pergularia tomentosa in North East Kingdom of Saudi Arabia KSA. Biomed. Pharmacol. J., 2018, 11(4)
[http://dx.doi.org/10.13005/bpj/1547]
[16]
Sewidan, N.; Abu Khalaf, R.; Mohammad, H.; Hammad, W. In-vitro studies on selected jordanian plants as dipeptidyl peptidase-IV inhibi-tors for management of diabetes mellitus. Iran. J. Pharm. Res., 2020, 19(4), 95-102.
[PMID: 33841525]
[17]
Katsarou, A.; Gudbjörnsdottir, S.; Rawshani, A.; Dabelea, D.; Bonifacio, E.; Anderson, B.J.; Jacobsen, L.M.; Schatz, D.A.; Lernmark, Å. Type 1 diabetes mellitus. Nat. Rev. Dis. Primers, 2017, 3(1), 17016.
[http://dx.doi.org/10.1038/nrdp.2017.16] [PMID: 28358037]
[18]
Chan, J.C.; Malik, V.; Jia, W.; Kadowaki, T.; Yajnik, C.S.; Yoon, K.H.; Hu, F.B. Diabetes in Asia: Epidemiology, risk factors, and patho-physiology. JAMA, 2009, 301(20), 2129-2140.
[http://dx.doi.org/10.1001/jama.2009.726] [PMID: 19470990]
[19]
Davidson, M.H. Potential impact of dipeptidyl peptidase-4 inhibitors on cardiovascular pathophysiology in type 2 diabetes mellitus. Postgrad. Med., 2014, 126(3), 56-65.
[http://dx.doi.org/10.3810/pgm.2014.05.2756] [PMID: 24918792]
[20]
Zimmet, P.; Alberti, K.G.; Magliano, D.J.; Bennett, P.H. Diabetes mellitus statistics on prevalence and mortality: Facts and fallacies. Nat. Rev. Endocrinol., 2016, 12(10), 616-622.
[http://dx.doi.org/10.1038/nrendo.2016.105] [PMID: 27388988]
[21]
Ahmad, M.N.; Farah, A.I.; Al-Qirim, T.M. The cardiovascular complications of diabetes: A striking link through protein glycation. Rom. J. Intern. Med., 2020, 58(4), 188-198.
[http://dx.doi.org/10.2478/rjim-2020-0021] [PMID: 32759408]
[22]
Kushwaha, R.; Haq, W.; Katti, S. discovery of 17 gliptins in 17-years of research for the treatment of type 2 diabetes: A synthetic over-view. Chem. Biol. Interact., 2014, 4(3), 137-162.
[23]
Khalaf, R.A. Exploring natural products as a source for antidiabetic lead compounds and possible lead optimization. Curr. Top. Med. Chem., 2016, 16(23), 2549-2561.
[http://dx.doi.org/10.2174/1568026616666160414123602] [PMID: 27086794]
[24]
Röhrborn, D.; Wronkowitz, N.; Eckel, J. DPP4 in Diabetes. Front. Immunol., 2015, 6, 386.
[http://dx.doi.org/10.3389/fimmu.2015.00386] [PMID: 26284071]
[25]
Pantaleão, S.Q.; Philot, E.A.; de Resende-Lara, P.T.; Lima, A.N.; Perahia, D.; Miteva, M.A.; Scott, A.L.; Honorio, K.M. Structural dynam-ics of DPP-4 and its influence on the projection of bioactive ligands. Molecules, 2018, 23(2), 490.
[http://dx.doi.org/10.3390/molecules23020490] [PMID: 29473857]
[26]
Yang, Y.; Shi, C.Y.; Xie, J.; Dai, J.H.; He, S.L.; Tian, Y. Identification of Potential Dipeptidyl Peptidase (DPP)-IV inhibitors among Moringa oleifera phytochemicals by virtual screening, molecular docking analysis, ADME/T-based prediction, and in vitro analyses. Molecules, 2020, 25(1), 189.
[http://dx.doi.org/10.3390/molecules25010189] [PMID: 31906524]
[27]
Green, B.D.; Flatt, P.R.; Bailey, C.J. Dipeptidyl peptidase IV (DPP IV) inhibi associations of dietary flavonoids with risk of type 2 diabe-tes, and markers of insulin resistance and systemic inflammation in women: A prospective study and cross-sectional analysistors: A new-ly emerging drug class for the treatment of type 2 diabetes. Diab. Vasc. Dis. Res., 2006, 3(3), 159-165.
[http://dx.doi.org/10.3132/dvdr.2006.024] [PMID: 17160910]
[28]
Guo, H.; Fang, C.; Huang, Y.; Pei, Y.; Chen, L.; Hu, J. The efficacy and safety of DPP4 inhibitors in patients with type 1 diabetes: A sys-tematic review and meta-analysis. Diabetes Res. Clin. Pract., 2016, 121, 184-191.
[http://dx.doi.org/10.1016/j.diabres.2016.08.022] [PMID: 27741478]
[29]
Inzucchi, S.E.; Bergenstal, R.M.; Buse, J.B.; Diamant, M.; Ferrannini, E.; Nauck, M.; Peters, A.L.; Tsapas, A.; Wender, R.; Matthews, D.R. Management of hyperglycemia in type 2 diabetes, 2015: A patient-centered approach: Update to a position statement of the American Dia-betes Association and the European Association for the Study of Diabetes. Diabetes Care, 2015, 38(1), 140-149.
[http://dx.doi.org/10.2337/dc14-2441] [PMID: 25538310]
[30]
Doupis, J. Linagliptin: From bench to bedside. Drug Des. Devel. Ther., 2014, 8, 431-446.
[http://dx.doi.org/10.2147/DDDT.S59523] [PMID: 24851042]
[31]
Song, Y.; Manson, J.E.; Buring, J.E.; Sesso, H.D.; Liu, S. Associations of dietary flavonoids with risk of type 2 diabetes, and markers of insulin resistance and systemic inflammation in women: A prospective study and cross-sectional analysis. J. Am. Coll. Nutr., 2005, 24(5), 376-384.
[http://dx.doi.org/10.1080/07315724.2005.10719488] [PMID: 16192263]
[32]
Eid, H.M.; Haddad, P.S. The antidiabetic potential of quercetin: Underlying mechanisms. Curr. Med. Chem., 2017, 24(4), 355-364.
[http://dx.doi.org/10.2174/0929867323666160909153707] [PMID: 27633685]
[33]
Bule, M.; Abdurahman, A.; Nikfar, S.; Abdollahi, M.; Amini, M. Antidiabetic effect of quercetin: A systematic review and meta-analysis of animal studies. Food Chem. Toxicol., 2019, 125, 494-502.
[http://dx.doi.org/10.1016/j.fct.2019.01.037] [PMID: 30735748]
[34]
Eid, H.M.; Martineau, L.C.; Saleem, A.; Muhammad, A.; Vallerand, D.; Benhaddou-Andaloussi, A.; Nistor, L.; Afshar, A.; Arnason, J.T.; Haddad, P.S. Stimulation of AMP-activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis-idaea. Mol. Nutr. Food Res., 2010, 54(7), 991-1003.
[http://dx.doi.org/10.1002/mnfr.200900218] [PMID: 20087853]
[35]
Alam, M.M.; Meerza, D.; Naseem, I. Protective effect of quercetin on hyperglycemia, oxidative stress and DNA damage in alloxan induced type 2 diabetic mice. Life Sci., 2014, 109(1), 8-14.
[http://dx.doi.org/10.1016/j.lfs.2014.06.005] [PMID: 24946265]
[36]
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(2), 117-123.
[http://dx.doi.org/10.1016/j.phrs.2004.06.002] [PMID: 15629256]
[37]
Stewart, L.K.; Wang, Z.; Ribnicky, D.; Soileau, J.L.; Cefalu, W.T.; Gettys, T.W. Failure of dietary quercetin to alter the temporal progres-sion of insulin resistance among tissues of C57BL/6J mice during the development of diet-induced obesity. Diabetologi, 2009, 52(3), 514-523.
[http://dx.doi.org/10.1007/s00125-008-1252-0] [PMID: 19142628]
[38]
Kobori, M.; Masumoto, S.; Akimoto, Y.; Takahashi, Y. Dietary quercetin allevia tes diabetic symptoms and reduces streptozotocin-induced disturbance of hepatic gene expression in mice. Mol. Nutr. Food Res., 2009, 53(7), 859-868.
[http://dx.doi.org/10.1002/mnfr.200800310] [PMID: 19496084]
[39]
Vessal, M.; Hemmati, M.; Vasei, M. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp. Biochem. Physiol, 2003, 135 C(3), 357-364.
[http://dx.doi.org/10.1016/S1532-0456(03)00140-6]
[40]
Eid, H.M.; Nachar, A.; Thong, F.; Sweeney, G.; Haddad, P.S. The molecular basis of the antidiabetic action of quercetin in cultured skele-tal muscle cells and hepatocytes. Pharmacogn. Mag., 2015, 11(41), 74-81.
[http://dx.doi.org/10.4103/0973-1296.149708] [PMID: 25709214]
[41]
Eitah, H.E.; Maklad, Y.A.; Abdelkader, N.F.; Gamal El Din, A.A.; Badawi, M.A.; Kenawy, S.A. Modulating impacts of quercetin/sitagliptin combination on streptozotocin-induced diabetes mellitus in rats. Toxicol. Appl. Pharmacol., 2019, 365, 30-40.
[http://dx.doi.org/10.1016/j.taap.2018.12.011] [PMID: 30576699]

Rights & Permissions Print Cite
Article Metrics
29
1
© 2024 Bentham Science Publishers | Privacy Policy