The Possible Role of Saponin in Type-II Diabetes- A Review

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Abstract

Background: The possible role of secondary metabolites in the management of diabetes is a great concern and constant discussion. This characteristic seems relevant and should be the subject of thorough discussion with respect to saponin.

Objective: The current data mainly focus on the impact of saponin in the treatment of type-II diabetes. The majority of studies emphasize on other secondary metabolites such as alkaloids and flavonoids, but very few papers are there representing the possible role of saponin as these papers express the narrow perspective of saponin phytoconstituents but lacking in providing the complete information on various saponin plants. The aim of the study was to summarize all available data concerning the saponin containing plant in the management of type-II diabetes.

Methods: All relevant papers on saponin were selected. This review summarizes the saponin isolation method, mechanism of action, clinical significance, medicinal plants and phytoconstituents responsible for producing a therapeutic effect in the management of diabetes.

Results: The saponin is of high potential with structural diversity and inhibits diabetic complications along with reducing the hyperglycemia through different mechanisms thereby providing scope for improving the existing therapy and developing the novel medicinal agents for curing diabetes.

Conclusion: Saponins having potential therapeutic benefits and are theorized as an alternative medication in decreasing serum blood glucose levels in the patient suffering from diabetes.

Keywords: Type-II diabetes, saponin, mechanism, clinical significance, medicinal plants, phytoconstituents.

[1]
LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: An endocrine society clinical practice Guideline. J Clin Endocrinol Metab 2019; 104(5): 1520-74.
[http://dx.doi.org/10.1210/jc.2019-00198] [PMID: 30903688]
[2]
World Health Organization. Global Report on Diabetes 2016; 978: 88.
[3]
Ghoul JE, Smiri M, Ghrab S, Boughattas NA, Ben-Attia M. Antihyperglycemic, antihyperlipidemic and antioxidant activities of traditional aqueous extract of Zygophyllum album in streptozotocin diabetic mice. Pathophysiology 2012; 19(1): 35-42.
[http://dx.doi.org/10.1016/j.pathophys.2011.12.001] [PMID: 22209473]
[4]
Srinivasan K. Plant foods in the management of diabetes mellitus: spices as beneficial antidiabetic food adjuncts. Int J Food Sci Nutr 2005; 56(6): 399-414.
[http://dx.doi.org/10.1080/09637480500512872] [PMID: 16361181]
[5]
Meliani N, Dib Mel A, Allali H, Tabti B. Hypoglycaemic effect of Berberis vulgaris L. in normal and streptozotocin-induced diabetic rats. Asian Pac J Trop Biomed 2011; 1(6): 468-71.
[http://dx.doi.org/10.1016/S2221-1691(11)60102-0] [PMID: 23569815]
[6]
Cho NH, Shaw JE, Karuranga S, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018; 138: 271-81.
[http://dx.doi.org/10.1016/j.diabres.2018.02.023] [PMID: 29496507]
[7]
El Barky A, Hussein SA. Saponins and their potential role in diabetes mellitus. Diabetes Mgmt 2017; 7(1): 148-58.
[8]
Marrelli M, Conforti F, Araniti F, Statti GA. Effects of saponins on lipid metabolism: A review of potential health benefits in the treatment of obesity. Molecules 2016; 21(10)E1404
[http://dx.doi.org/10.3390/molecules21101404] [PMID: 27775618]
[9]
Vinarov Z, Radeva D, Katev V, Tcholakova S, Denkov N. Solubilisation of hydrophobic drugs by saponins. Indian J Pharm Sci 2018; 80(4): 709-18.
[http://dx.doi.org/10.4172/pharmaceutical-sciences.1000411]
[10]
Moghimipour E, Handali S. Saponin: Properties, methods of evaluation and applications. Annu Res Rev Biol 2014; 5(3): 207-20.
[http://dx.doi.org/10.9734/ARRB/2015/11674]
[11]
Ahlberg V, Hjertner B, Wallgren P, Hellman S, Lövgren Bengtsson K, Fossum C. Innate immune responses induced by the saponin adjuvant Matrix-M in specific pathogen free pigs. Vet Res (Faisalabad) 2017; 48(1): 30.
[http://dx.doi.org/10.1186/s13567-017-0437-2] [PMID: 28532492]
[12]
Cibulski SP, Rivera-Patron M, Mourglia-Ettlin G, et al. Quillaja brasiliensis saponin-based nanoparticulate adjuvants are capable of triggering early immune responses. Sci Rep 2018; 8(1): 13582.
[http://dx.doi.org/10.1038/s41598-018-31995-1] [PMID: 30206376]
[13]
Ahhmed A, Baek JS, Kim JD, Kim MY, Khan MI, Shin JH. Green Tea Seed Isolated Saponins Exerts Antibacterial Effects against Various Strains of Gram Positive and Gram Negative Bacteria, a Comprehensive Study In Vitro and In Vivo. Evid-Based Compl Alt 2018; pp. 1-12.
[14]
Ravi L. V M, B PL. Antibacterial and antioxidant activity of saponin from Abutilon indicum leaves. Asian J Pharmaceut Clin Res 2017; 9(3): 344-7.
[15]
Nafiu MO, Ashafa AOT. Antioxidant and inhibitory effects of saponin extracts from Dianthus basuticus Burtt Davy on key enzymes implicated in type 2 diabetes in vitro. Pharmacogn Mag 2017; 13(52): 576-82.
[http://dx.doi.org/10.4103/pm.pm_583_16] [PMID: 29200716]
[16]
Al-Snafi AE. Chemical constituents and pharmacological effects of Chenopodium album -an overview. Int J Pharmacol Screen Methods 2015; 5(1): 10-7.
[17]
Yu Z, Zhang T, Zhou F, Xiao X, Ding X, He H, et al. Anticancer activity of saponins from allium chinense against the B16 melanoma and 4T1 breast carcinoma cell. Evid-Based Compl Alt 2015; pp. 1-12.
[18]
Koczurkiewicz P, Czyż J, Podolak I, et al. Multidirectional effects of triterpene saponins on cancer cells - mini-review of in vitro studies. Acta Biochim Pol 2015; 62(3): 383-93.
[http://dx.doi.org/10.18388/abp.2015_1089] [PMID: 26307770]
[19]
Yildirim I, Kutlu T. Anticancer agents: Saponin and tannin. Int J Biol Chem 2015; 9(6): 332-40.
[http://dx.doi.org/10.3923/ijbc.2015.332.340]
[20]
El-Naggar SA, Germoush MO, Abdel-Farid IB, Lgebaly HA. Phytochemical analysis and anticancer screening of some indigenous plants grown in Saudi Arabia. J Cancer Biomed Res 2018; 1(1): 19-27.
[http://dx.doi.org/10.21608/jcbr.2019.34741]
[21]
Elekofehinti OO. Saponins: Anti-diabetic principles from medicinal plants - A review. Pathophysiology 2015; 22(2): 95-103.
[http://dx.doi.org/10.1016/j.pathophys.2015.02.001] [PMID: 25753168]
[22]
Sani UM. Phytochemical screening and antidiabetic effect of extracts of the seeds of Citrullus lanatus in alloxan-induced diabetic albino mice. J Appl Pharm Sci 2015; 5(3): 51-64.
[http://dx.doi.org/10.7324/JAPS.2015.50309]
[23]
Khan N, Akhtar MS, Khan BA, Braga Vde A, Reich A. Antiobesity, hypolipidemic, antioxidant and hepatoprotective effects of Achyranthes aspera seed saponins in high cholesterol fed albino rats. Arch Med Sci 2015; 11(6): 1261-71.
[http://dx.doi.org/10.5114/aoms.2015.56353] [PMID: 26788089]
[24]
Md AHMMR. Mahfuzur Rahman. Medicinal plants having anti-obesity potentiality available in Bangladesh: A review. Biol Med Case Rep 2017; 1(2): 4-11.
[25]
Desai S, Kaur H. Saponins and their biological activities. Pharm Times 2017; 41(3): 12-6.
[26]
Faizal A, Geelen D. Saponins and their role in biological processes in plants. Phytochem Rev 2013; 12(4): 877-93.
[http://dx.doi.org/10.1007/s11101-013-9322-4]
[27]
Cheok CY, Salman HAK, Sulaiman R. Extraction and quantification of saponins: A review. Food Res Int 2014; 59: 16-40.
[http://dx.doi.org/10.1016/j.foodres.2014.01.057]
[28]
Care D, Suppl SS. American Diabetes Association. 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes. Diabetes Care 2019; 42(1)(Suppl. 1): S13-28.
[PMID: 30559228]
[29]
Abdal Dayem A, Hossain MK, Lee SB, et al. The role of reactive oxygen species (ROS) in the biological activities of metallic nanoparticles. Int J Mol Sci 2017; 18(1): 1-21.
[http://dx.doi.org/10.3390/ijms18010120] [PMID: 28075405]
[30]
Zhou J, Liu YY, Tang Y, Liu F, Zhang L, Zeng X, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Int Urol Nephrol 2017; 10(1): 1-6.
[31]
Held BP, Instruments B. An Introduction to Reactive Oxygen species measurement of ROS in yeast cells. Biotek 2015; pp. 1-21.
[32]
Guilbaud A, Niquet-Leridon C, Boulanger E, Tessier FJ. How can diet affect the accumulation of advanced glycation end-products in the human body. Foods 2016; 5(4)E84
[http://dx.doi.org/10.3390/foods5040084] [PMID: 28231179]
[33]
Hanssen NMJ, Beulens JWJ, van Dieren S, et al. Plasma advanced glycation end products are associated with incident cardiovascular events in individuals with type 2 diabetes: a case-cohort study with a median follow-up of 10 years (EPIC-NL). Diabetes 2015; 64(1): 257-65.
[http://dx.doi.org/10.2337/db13-1864] [PMID: 24848072]
[34]
Geraldes P, King GL. Activation of protein kinase C isoforms and its impact on diabetic complications. Circ Res 2010; 106(8): 1319-31.
[http://dx.doi.org/10.1161/CIRCRESAHA.110.217117] [PMID: 20431074]
[35]
Noh H, King GL. The role of protein kinase C activation in diabetic nephropathy. Kidney Int Suppl 2007; 72(106): S49-53.
[http://dx.doi.org/10.1038/sj.ki.5002386] [PMID: 17653211]
[36]
Yan LJ. Redox imbalance stress in diabetes mellitus: Role of the polyol pathway. Animal Model Exp Med 2018; 1(1): 7-13.
[http://dx.doi.org/10.1002/ame2.12001] [PMID: 29863179]
[37]
Zheng T, Shu G, Yang Z, Mo S, Zhao Y, Mei Z. Antidiabetic effect of total saponins from Entada phaseoloides (L.) Merr. in type 2 diabetic rats. J Ethnopharmacol 2012; 139(3): 814-21.
[http://dx.doi.org/10.1016/j.jep.2011.12.025] [PMID: 22212505]
[38]
Lavle N, Shukla P, Panchal A. Role of Flavonoids and saponins in the treatment of diabetes mellitus. J Pharm Sci Bioscientific Res 2016; 64(6): 535-41.
[39]
Kwon DY, Kim YS, Ryu SY, et al. Platyconic acid, a saponin from Platycodi radix, improves glucose homeostasis by enhancing insulin sensitivity in vitro and in vivo. Eur J Nutr 2012; 51(5): 529-40.
[http://dx.doi.org/10.1007/s00394-011-0236-x] [PMID: 21847688]
[40]
Deshpande HA, Bhalsing SR. Plant derived novel biomedicinal: Diosgenin. Int J Pharmacog Phytochem Res 2014; 6(4): 780-94.
[41]
Habicht SD, Kind V, Rudloff S, Borsch C, Mueller AS, Pallauf J, et al. Quantification of antidiabetic extracts and compounds in bitter gourd varieties. Food Chem 2011; 126(1): 172-86.
[http://dx.doi.org/10.1016/j.foodchem.2010.10.094]
[42]
Moses T, Papadopoulou KK, Osbourn A. Metabolic and functional diversity of saponins, biosynthetic intermediates and semi-synthetic derivatives. Crit Rev Biochem Mol Biol 2014; 49(6): 439-62.
[http://dx.doi.org/10.3109/10409238.2014.953628] [PMID: 25286183]
[43]
Ojo AB, Adanlawo IG, Ojo OA. Efficacy of saponins from Helianthus annuus roots on antihyperglycemic, antiperoxidative and antihyperlipidemic effects in alloxan-induced diabetic rats. Int J Pharmacog Phytochem Res 2017; 9(1): 83-98.
[http://dx.doi.org/10.25258/ijpapr.v9i1.8045]
[44]
Elekofehinti OO. Saponins: Anti-diabetic principles from medicinal plants - A review. Pathophysiology 2015; 22(2): 95-103.
[http://dx.doi.org/10.1016/j.pathophys.2015.02.001] [PMID: 25753168]
[45]
Hị Hong Hanh T, Hai Dang N, Tien Dat N. α -Amylase and α -Glucosidase inhibitory saponins from Polyscias fruticosa leaves. J Chem-NY 2016; 8(7): 337-49.
[46]
Yin Z, Zhang W, Feng F, Zhang Y, Kang W. α-Glucosidase inhibitors isolated from medicinal plants. Food Sci Hum Wellness 2014; 3(4): 136-74.
[http://dx.doi.org/10.1016/j.fshw.2014.11.003]
[47]
Deng Y, He K, Ye X, et al. Saponin rich fractions from Polygonatum odoratum (Mill.) Druce with more potential hypoglycemic effects. J Ethnopharmacol 2012; 141(1): 228-33.
[http://dx.doi.org/10.1016/j.jep.2012.02.023] [PMID: 22366676]
[48]
Guo Y, Han X, Che H, et al. Synergistic effect of eicosapentaenoic acid-enriched phospholipids and sea cucumber saponin on orotic acid-induced non-alcoholic fatty liver disease in rats. R Soc Open Sci 2018; 5(7)172182
[http://dx.doi.org/10.1098/rsos.172182] [PMID: 30109054]
[49]
Xu J, Wang S, Feng T, Chen Y, Yang G. Hypoglycemic and hypolipidemic effects of total saponins from Stauntonia chinensis in diabetic db/db mice. J Cell Mol Med 2018; 22(12): 6026-38.
[http://dx.doi.org/10.1111/jcmm.13876] [PMID: 30324705]
[50]
Petit B, Mitaine-Offer AC, Delaude C, Miyamoto T, Tanaka C, Lacaille-Dubois MA. Hederagenin glycosides from the fruits of Blighia unijugata. Phytochemistry 2019; 162(3): 260-9.
[http://dx.doi.org/10.1016/j.phytochem.2019.03.020] [PMID: 31031211]
[51]
Majinda RRT. Extraction and isolation of saponins. Methods Mol Biol 2012; 864: 415-26.
[http://dx.doi.org/10.1007/978-1-61779-624-1_16] [PMID: 22367906]
[52]
Ramesh AS, Christopher JG, Radhika R, Setty CR, Thankamani V. Isolation, characterisation and cytotoxicity study of arjunolic acid from Terminalia arjuna. Nat Prod Res 2012; 26(16): 1549-52.
[http://dx.doi.org/10.1080/14786419.2011.566870] [PMID: 21732908]
[53]
Bhakuni RS, Shukla YN, Tripathi AK, Prajapati V, Kumar S. Insect growth inhibitor activity of arjunolic acid isolated from Cornus capitata. Phytother Res 2002; 16(Suppl. 1): S68-70.
[http://dx.doi.org/10.1002/ptr.748] [PMID: 11933143]
[54]
Hemalatha T, Pulavendran S, Balachandran C, Manohar BM, Puvanakrishnan R. Arjunolic acid: a novel phytomedicine with multifunctional therapeutic applications. Indian J Exp Biol 2010; 48(3): 238-47.
[PMID: 21046976]
[55]
Manna P, Sil PC. Arjunolic acid: beneficial role in type 1 diabetes and its associated organ pathophysiology. Free Radic Res 2012; 46(7): 815-30.
[http://dx.doi.org/10.3109/10715762.2012.683431] [PMID: 22486656]
[56]
Manna P, Sinha M, Sil PC. Prophylactic role of arjunolic acid in response to streptozotocin mediated diabetic renal injury: activation of polyol pathway and oxidative stress responsive signaling cascades. Chem Biol Interact 2009; 181(3): 297-308.
[http://dx.doi.org/10.1016/j.cbi.2009.08.004] [PMID: 19682444]
[57]
Carella AM. Hypoglycemia by Ginseng in type 2 Diabetic Patient: Case Report. New Insights in Obes Gene Beyond 2017; 1: 1-6.
[http://dx.doi.org/10.29328/journal.hodms.1001001]
[58]
Agyemang K, Han L, Liu E, Zhang Y, Wang T, Gao X. Anti-Diabetic Research: Pharmacological Effects of Its Phytochemical Constituents. Evid-Based Compl. Alt 2013; pp. 643-53.
[59]
Song G, Han P, Sun H, et al. Astragaloside IV ameliorates early diabetic nephropathy by inhibition of MEK1/2-ERK1/2-RSK2 signaling in streptozotocin-induced diabetic mice. J Int Med Res 2018; 46(7): 2883-97.
[http://dx.doi.org/10.1177/0300060518778711] [PMID: 29896981]
[60]
Lu WS, Li S, Guo WW, Chen LL, Li YS. Effects of Astragaloside IV on diabetic nephropathy in rats. Genet Mol Res 2015; 14(2): 5427-34.
[http://dx.doi.org/10.4238/2015.May.22.12] [PMID: 26125738]
[61]
Lv L, Wu SY, Wang GF, et al. Effect of astragaloside IV on hepatic glucose-regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin. Phytother Res 2010; 24(2): 219-24.
[PMID: 19610026]
[62]
Desai S, Tatke P. Charantin: An important lead compound from Momordica charantia for the treatment of diabetes. J Pharmacog Phytochem 2015; 3(6): 163-76.
[63]
Zaini AS, Aris NA, Putra NR, Abd Hashib S, Kamaruddin MJ, Idham Z, et al. Comparison of charantin extract from Momordica charantia using modified supercritical carbon dioxide and soxhlet extraction method. Malaya J Appl Sci 2019; 14(4): 462-6.
[http://dx.doi.org/10.11113/mjfas.v14n4.1092]
[64]
Nagappan K, Anoop K, Kowmudi G, Sailaja M. Charantin: A neglected antidiabetic compound from Momordica charantia L. Int J Pharm Sci Rev Res 2018; 51(7): 35-40.
[65]
Joseph B, Jini D. Antidiabetic effects of Momordica charantia (bitter melon) and its medicinal potency. Asian Pac J Trop Dis 2013; 3(2): 93-102.
[http://dx.doi.org/10.1016/S2222-1808(13)60052-3]
[66]
Ads EN, Rajendrasozhan S, Hassan SI, Sharawy SMS, Humaidi JR. Phytochemical, antimicrobial and cytotoxic evaluation of Ziziphus spina-christi (L.) stem bark. Biomed Res (Aligarh) 2017; 28(15): 6646-53.
[67]
Michel CG, Nesseem DI, Ismail MF. Anti-diabetic activity and stability study of the formulated leaf extract of Zizyphus spina-christi (L.) Willd with the influence of seasonal variation. J Ethnopharmacol 2011; 133(1): 53-62.
[http://dx.doi.org/10.1016/j.jep.2010.09.001] [PMID: 20833236]
[68]
Governa P, Baini G, Borgonetti V, et al. Phytotherapy in the management of diabetes: A review. Molecules 2018; 23(1): 1-22.
[http://dx.doi.org/10.3390/molecules23010105] [PMID: 29300317]
[69]
Avalos-Soriano A, De la Cruz-Cordero R, Rosado JL, Garcia-Gasca T. 4-Hydroxyisoleucine from fenugreek (Trigonella foenum-graecum): Effects on insulin resistance associated with obesity. Molecules 2016; 21(11): 1-12.
[http://dx.doi.org/10.3390/molecules21111596] [PMID: 27879673]
[70]
Uemura T, Goto T, Kang M-S, et al. Diosgenin, the main aglycon of fenugreek, inhibits LXRα activity in HepG2 cells and decreases plasma and hepatic triglycerides in obese diabetic mice. J Nutr 2011; 141(1): 17-23.
[http://dx.doi.org/10.3945/jn.110.125591] [PMID: 21106928]
[71]
Kanchan DM, Somani GS, Peshattiwar VV, Kaikini AA, Sathaye S. Renoprotective effect of diosgenin in streptozotocin induced diabetic rats. Pharmacol Rep 2016; 68(2): 370-7.
[http://dx.doi.org/10.1016/j.pharep.2015.10.011] [PMID: 26922541]
[72]
Roghani-Dehkordi F, Roghani M, Baluchnejadmojarad T. Diosgenin mitigates streptozotocin diabetes-induced vascular dysfunction of the rat aorta: The involved mechanisms. J Cardiovasc Pharmacol 2015; 66(6): 584-92.
[http://dx.doi.org/10.1097/FJC.0000000000000308] [PMID: 26309100]
[73]
Gaikwad SB, Krishna Mohan G, Sandhya Rani M. Phytochemicals for diabetes management. Pharmaceut Crops 2014; 5: 11-28.
[http://dx.doi.org/10.2174/2210290601405010011]
[74]
Li Y, Liu Y, Liang J, Wang T, Sun M, Zhang Z. Gymnemic acid ameliorates hyperglycemia through PI3K/AKT- and AMPK-mediated signaling pathways in Type 2 diabetes mellitus rats. J Agric Food Chem 2019; 67(47): 13051-60.
[http://dx.doi.org/10.1021/acs.jafc.9b04931] [PMID: 31609623]
[75]
Jia S, Shen M, Zhang F, Xie J. Recent advances in momordica charantia: Functional components and biological activities. Int J Mol Sci 2017; 18(12): 25-55.
[http://dx.doi.org/10.3390/ijms18122555] [PMID: 29182587]
[76]
Luo JG, Ma L, Kong LY. New triterpenoid saponins with strong alpha-glucosidase inhibitory activity from the roots of Gypsophila oldhamiana. Bioorg Med Chem 2008; 16(6): 2912-20.
[http://dx.doi.org/10.1016/j.bmc.2007.12.053] [PMID: 18194870]
[77]
Guo T, Wu S, Guo S, Bai L, Liu Q, Bai N. Synthesis and Evaluation of a Series of Oleanolic Acid Saponins as α-Glucosidase and α-Amylase Inhibitors. Arch Pharm (Weinheim) 2015; 348(9): 615-28.
[http://dx.doi.org/10.1002/ardp.201500179] [PMID: 26207761]
[78]
Patel DK, Kumar R, Laloo D, Hemalatha S. Natural medicines from plant source used for therapy of diabetes mellitus: An overview of its pharmacological aspects. Asian Pac J Trop Dis 2012; 2(4): 239-50.
[http://dx.doi.org/10.1016/S2222-1808(12)60054-1]
[79]
Zhou P, Xie W, He S, et al. Ginsenoside Rb1 as an anti-diabetic agent and its underlying mechanism analysis. Cells 2019; 8(3): 204.
[http://dx.doi.org/10.3390/cells8030204] [PMID: 30823412]
[80]
Bai L, Gao J, Wei F, Zhao J, Wang D, Wei J. Therapeutic potential of ginsenosides as an adjuvant treatment for diabetes. Front Pharmacol 2018; 9: 423.
[http://dx.doi.org/10.3389/fphar.2018.00423] [PMID: 29765322]
[81]
Naseem M, Nazih H, Ouguerram K, Rabbani I, Sciences A. The effects of Panax ginseng root extract on carbohydrate and lipid disturbances associated with alloxan-induced diabetic rats. J Anim Plant Sci 2016; 26(1): 45-89.
[82]
Mohammed A, Kumar D, Rizvi SI. Emergence of traditional antidiabetic treatments as starting points for development of modern medicine. J Exp Integr Med 2015; 5(3): 121-7.
[http://dx.doi.org/10.5455/jeim.160615.rw.012]
[83]
Patel DK, Prasad SK, Kumar R, Hemalatha S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac J Trop Biomed 2012; 2(4): 320-30.
[http://dx.doi.org/10.1016/S2221-1691(12)60032-X] [PMID: 23569923]
[84]
Sunil K. Manjusha Choudhary, Priya Yadav N and VB. Anti-diabetic activity of hydroalcoholic extract of Acacia melanoxylon Linn. seeds in streptozotocin induced diabetic rats. J Diabetes Metab 2016; •••: 5-7.
[85]
Mukundi MJ. Antidiabetic effects of aqueous leaf extracts of acacia nilotica in alloxan induced diabetic mice. J Diabetes Metab 2015; 6(7): 1-6.
[http://dx.doi.org/10.4172/2155-6156.1000568] [PMID: 26819810]
[86]
Talukder FZ, Khan KA, Uddin R, Jahan N, Alam MA, Alam A. In vitro free radical scavenging and anti-hyperglycemic activities of Achyranthes aspera extract in alloxan-induced diabetic mice. Drug Discov Ther 2012; 6(6): 298-305.
[http://dx.doi.org/10.5582/ddt.2012.v6.6.298] [PMID: 23337817]
[87]
Tafesse TB, Hymete A, Mekonnen Y, Tadesse M. Antidiabetic activity and phytochemical screening of extracts of the leaves of Ajuga remota Benth on alloxan-induced diabetic mice. BMC Complement Altern Med 2017; 17(1): 243.
[http://dx.doi.org/10.1186/s12906-017-1757-5] [PMID: 28464813]
[88]
Patel PA, Parikh MP, Johari S, Gandhi TR. Antihyperglycemic activity of Albizzia lebbeck bark extract in streptozotocin-nicotinamide induced type II diabetes mellitus rats. Ayu 2015; 36(3): 335-40.
[http://dx.doi.org/10.4103/0974-8520.182752] [PMID: 27313423]
[89]
Cabrera W, Genta S, Said A, Farag A, Rashed K, Sánchez S. Hypoglycemic activity of Ailanthus excelsa leaves in normal and streptozotocin-induced diabetic rats. Phytother Res 2008; 22(3): 303-7.
[http://dx.doi.org/10.1002/ptr.2311] [PMID: 18058975]
[90]
Ozougwu JC. Anti-Diabetic effects of Allium cepa (Onions) aqueous extracts on alloxan-Induced diabetic. J Med Plants Res 2011; 5(7): 1134-9.
[91]
Rind NA, Dahot MU, Malik SA, Kumar M, Bhutto MA, Rafiq M. Comparative antihyperglycemic activity of aqueous extracts of garlic (Allium sativum) and ginger (Zingiber officinale) in alloxan-induced male rabbits. Pak J Biotechnol 2013; 10(2): 53-62.
[92]
Metwally NS, Mohamed AM, El Sharabasy FS. Chemical constituents of the Egyptian plant Anabasis articulata (Forssk) moq and its antidiabetic effects on rats with streptozotocininduced diabetic hepatopathy. J Appl Pharm Sci 2012; 2(4): 54-65.
[93]
Chaouki Selles. Anti-diabetic activity of aqueous root extract of Anacyclus pyrethrum L. in streptozotocin-induced-diabetic rats. J Med Plants Res 2012; 6(16): 1-7.
[94]
Mondal S, Bhattacharya S, Biswas M. Antidiabetic activity of Areca catechu leaf extracts against streptozotocin induced diabetic rats. J Adv Pharm Educ Res 2012; 2(1): 10-7.
[95]
Zhang K, Pugliese M, Pugliese A, Passantino A. Biological active ingredients of traditional Chinese herb Astragalus membranaceus on treatment of diabetes: a systematic review. Mini Rev Med Chem 2015; 15(4): 315-29.
[http://dx.doi.org/10.2174/1389557515666150227113431] [PMID: 25723453]
[96]
Debnath T, Radhakrishnan R, Murugananthan G, Talwar SKN. Hypoglycaemic effects of alcoholic root extract of Borassus flabellifer (Linn.) in normal and diabetic rats. Pak J Pharm Sci 2013; 26(4): 673-9.
[PMID: 23811441]
[97]
G SPK Kasireddy GR. Anil C, Sathish D, Bhavani E. Anti-diabetic properties of the methanolic leaf extract of Bougainvillea glabra on alloxan-induced diabetic rats. J Dent Med Sci 2017; 16(11): 8-13.
[98]
Widhiantara IG, Arunngam P, Milas Siswanto F. Ethanolic extract of Caesalpinia bonducella f. seed ameliorates diabetes phenotype of streptozotocin- nicotinamide-induced type 2 diabetes rat. Biomed Pharmacol J 2018; 11(2): 1127-33.
[http://dx.doi.org/10.13005/bpj/1473]
[99]
Manzo JAM, Vitor RJS. Antihyperglycemic effects of Cajanus cajan L. (pigeon pea) ethanolic extract on the blood glucose levels of ICR mice (Mus musculus l.). J Physiol Pharm Pharmacol 2017; 7(8): 860-4.
[http://dx.doi.org/10.5455/njppp.2017.7.0410801052017]
[100]
Ezike AC, Akah PA, Okoli CC, Okpala CB. Experimental evidence for the antidiabetic activity of cajanus cajan leaves in rats. J Basic Clin Pharm 2010; 1(2): 81-4.
[PMID: 24825970]
[101]
Ripa FA, Dash PR, Podder AK. Anti-diarrheal and hypoglycemic activities of methanol extract of Calamus rotang L. seed in rat. Res J Pharmacog 2016; 3(2): 33-40.
[102]
Odoh UE, Onugha VO, Chukwube VO. Evaluation of antidiabetic effect and hematotological profile of methanol extract of Ceiba pentandra G (Malvaceae) stem bark on alloxan-induced diabetic rats. Afr J Pharm Pharmacol 2016; 10: 584-90.
[http://dx.doi.org/10.5897/AJPP2015.4469]
[103]
Satyaprakash RJ, Rajesh MS, Bhanumathy M, et al. Hypoglycemic and antihyperglycemic effect of Ceiba pentandra L. Gaertn in normal and streptozotocin-induced diabetic rats. Ghana Med J 2013; 47(3): 121-7.
[PMID: 24391227]
[104]
Sahane RS, Wankhade PA, Shrungarpure MA. Investigation of Cestrum nocturnum leaf extract for antihyperglycemic and antihyperlipidemic activity. Int J Res Pharmacol Phytochem 2014; 3(4): 255-68.
[105]
Singh S, Ali S, Singh M. Pharmacological potential of Tricosanthes tricuspidata and Clematis montana for hypoglycemic and antioxidant activity. European J Med Plants 2015; 6(3): 175-80.
[http://dx.doi.org/10.9734/EJMP/2015/12769]
[106]
Helal EGE, AbouAouf N, Abdallah IZA. Khattab AlM. Hypoglycemic and antioxidant effects of Cleome droserifolia in alloxan-induced diabetic rats. Egypt J Hosp Med 2015; 58: 39-47.
[http://dx.doi.org/10.12816/0009359]
[107]
Ramakrishnan M, Bhuvaneshwari R, Duraipandiyan V, Dhandapani R. Hypoglycaemic activity of Coccinia indica fruits in alloxan-induced diabetic rats. Indian J Nat Prod Resour 2011; 2(3): 350-3.
[108]
Vadivel E, Panwal SV. Antidiabetic and anthelmintic activity of Crossandra infundibuliformis. Int J Pharm Tech 2016; 8(3): 67-74.
[109]
Liu W, Deng S, Zhou D, et al. 3,4-seco-Dammarane Triterpenoid Saponins with Anti-Inflammatory Activity Isolated from the Leaves of Cyclocarya paliurus. J Agric Food Chem 2020; 68(7): 2041-53.
[http://dx.doi.org/10.1021/acs.jafc.9b06898] [PMID: 31967813]
[110]
Wang Q, Jiang C, Fang S, et al. Antihyperglycemic, antihyperlipidemic and antioxidant effects of ethanol and aqueous extracts of Cyclocarya paliurus leaves in type 2 diabetic rats. J Ethnopharmacol 2013; 150(3): 1119-27.
[http://dx.doi.org/10.1016/j.jep.2013.10.040] [PMID: 24184190]
[111]
Roy A, Geetha RV. Invitro α-amylase and α-glucosidase inhibitory activities of the ethanolic extract of Dioscorea Villosa tubers. Int J Pharma Bio Sci 2013; 4(4): 1-9.
[112]
Krishnaveni kante and Challa Srinivas Reddy. Anti diabetic activity of Dolichos lablab (seeds) in Streptozotocin- Nicotinamide induced diabetic rats. J Drugs Med 2013; 5: 32-40.
[113]
Zheng T, Shu G, Yang Z, Mo S, Zhao Y, Mei Z. Antidiabetic effect of total saponins from Entada phaseoloides (L.) Merr. in type 2 diabetic rats. J Ethnopharmacol 2012; 139(3): 814-21.
[http://dx.doi.org/10.1016/j.jep.2011.12.025] [PMID: 22212505]
[114]
Gayathri M, Kannabiran K. Antidiabetic and ameliorative potential of Ficus bengalensis bark extract in streptozotocin induced diabetic rats. Indian J Clin Biochem 2008; 23(4): 394-400.
[http://dx.doi.org/10.1007/s12291-008-0087-2] [PMID: 23105795]
[115]
Singh AK, Singh J. Evaluation of anti-diabetic potential of leaves and stem of Flacourtia jangomas in streptozotocin-induced diabetic rats. Indian J Pharmacol 2010; 42(5): 301-5.
[http://dx.doi.org/10.4103/0253-7613.70238] [PMID: 21206623]
[116]
Smith YA, Adanlawo IG, Oni OS, Oni OS. Hypoglycaemic effect of saponin from the root of Garcinia kola (bitter kola) on alloxan-induced diabetic rats. J Drug Deliv Ther 2012; 2(6): 1-8.
[http://dx.doi.org/10.22270/jddt.v2i6.338]
[117]
Patel P, Harde P, Pillai J, Darji N, Patel B. Antidiabetic herbal drugs a review. Pharmacophore 2012; 3(1): 18-24.
[118]
Saini S, Sharma S. Antidiabetic effect of Helianthus annuus L., seeds ethanolic extract in streptozotocin- nicotinamide induced type 2 diabetes mellitus. Int J Pharm Pharm Sci 2013; 5(2): 382-7.
[119]
Bhavsar SK, Singh S, Giri S, Jain MR, Santani DD. Effect of saponins from Helicteres isora on lipid and glucose metabolism regulating genes expression. J Ethnopharmacol 2009; 124(3): 426-33.
[http://dx.doi.org/10.1016/j.jep.2009.05.041] [PMID: 19505560]
[120]
Hridi SU, Ferdous N, Majumder FU, Hannan JMA. Phytochemical screening and anti-diabetic efficacy of stem of Hiptage benghalensis (L) Kurz. J Sci Innov Res 2013; 2(4): 736-44.
[121]
Tanko Y, Abdelaziz MM, Adelaiye AB, Fatihu MY, Musa KY. Effects of hydromethanolic leaves extract of Indigofera pulchra on blood glucose levels of normoglycemic and alloxan-induced diabetic Wistar rats. Int J Appl Res Nat Prod 2008; 1(4): 13-8.
[122]
Akhtar N, Akram M, Daniyal M, Ahmad S. Evaluation of antidiabetic activity of Ipomoea batatas L extract in alloxan-induced diabetic rats. Int J Immunopath Ph 2018; p. 32.
[123]
Samanta S, Chanda R, Reddy AG. Anti-diabetic activity of mango (Mangifera indica): a review. MOJ Bioequiv 2019; 6(2): 23-6.
[124]
Basha DP, Kumar KP, Teja BB, Subbarao M. Antidiabetic activity on extracts of Mangifera indica in Alloxan monohydrate induced diabetic rats. Drug InventToday 2011; 3(7): 165-8.
[125]
Siboto A, Sibiya N, Khathi A, Ngubane P. The Effects of Momordica balsamina Methanolic Extract on Kidney Function in STZ-Induced Diabetic Rats: Effects on Selected Metabolic Markers. J Diabetes Res 2018.20187341242
[http://dx.doi.org/10.1155/2018/7341242] [PMID: 30009183]
[126]
Koneri RB, Samaddar S, Ramaiah CT. Antidiabetic activity of a triterpenoid saponin isolated from Momordica cymbalaria Fenzl. Indian J Exp Biol 2014; 52(1): 46-52.
[PMID: 24624483]
[127]
Owolabi O, Amaechina F, Okoro M. Effect of ethanol leaf extract of Newboulda laevis on blood glucose levels of diabetic rats. Trop J Pharm Res 2011; 10(3): 249-54.
[http://dx.doi.org/10.4314/tjpr.v10i3.12]
[128]
Danladi S, Idris M. Review on pharmacological activities and phytochemical constituents of Phyllanthus niruri (Amarus). J Phytopharmacol 2018; 7(3): 341-8.
[129]
Okoli CO. Ibiam, Akah PA, Okoye TC. Evaluation of antidiabetic potentials of Phyllanthus niruri in alloxan diabetic rats. Afr J Biotechnol 2010; 9(2): 248-59.
[130]
Bnouham M, Ziyyat A, Mekhfi H, Tahri A, Legssyer A. Medicinal plants with potential antidiabetic activity - A review of ten years of herbal medicine research (1990-2000). Int J Diabetes Metab 2006; 14(1): 1-25.
[http://dx.doi.org/10.1159/000497588]
[131]
Singh S, Farswan M, Ali S, et al. Antidiabetic potential of triterpenoid saponin isolated from Primula denticulate. Pharm Biol 2014; 52(6): 750-5.
[http://dx.doi.org/10.3109/13880209.2013.869759] [PMID: 24617737]
[132]
Liu YW, Zhu X, Lu Q, et al. Total saponins from Rhizoma Anemarrhenae ameliorate diabetes-associated cognitive decline in rats: involvement of amyloid-beta decrease in brain. J Ethnopharmacol 2012; 139(1): 194-200.
[http://dx.doi.org/10.1016/j.jep.2011.11.004] [PMID: 22101084]
[133]
Barky EA. Ali, Mohamed. Marine Sea Cucumber Saponins and Diabetes. Austin Pancreat Disord 2017; 1(1): 1002.
[134]
Ali MA, Wahed MI, Khatune NA, Rahman BM, Barman RK, Islam MR. Antidiabetic and antioxidant activities of ethanolic extract of Semecarpus anacardium (Linn.) bark. BMC Complement Altern Med 2015; 15(4): 138-45.
[http://dx.doi.org/10.1186/s12906-015-0662-z] [PMID: 25925864]
[135]
Elekofehinti OO, Kamdem JP, Kade IJ, Rocha JBT, Adanlawo IG. Hypoglycemic, antiperoxidative and antihyperlipidemic effects of saponins from Solanum anguivi Lam. fruits in alloxan-induced diabetic rats. S Afr J Bot 2013; 88: 56-61.
[http://dx.doi.org/10.1016/j.sajb.2013.04.010]
[136]
Elosh G, Palanivel V, Kl SK. Evaluation of Anti-diabetic activity of Tecoma stans stem extract in induced diabetic albino rats. Int J Innov Pharmaceut Res 2013; 4(3): 337-41.
[137]
El-Shaibany A, Al-Habori M, Al-Tahami B, Al-Massarani S. Anti-hyperglycaemic activity of Tribulus terrestris L aerial part extract in glucose-loaded normal rabbits. Trop J Pharm Res 2015; 14(12): 2263-8.
[http://dx.doi.org/10.4314/tjpr.v14i12.16]
[138]
Zhang H, Tong WT, Zhang CR, et al. Gross saponin of Tribulus terrestris improves erectile dysfunction in type 2 diabetic rats by repairing the endothelial function of the penile corpus cavernosum. Diabetes Metab Syndr Obes 2019; 12: 1705-16.
[http://dx.doi.org/10.2147/DMSO.S205722] [PMID: 31564938]
[139]
Neelakantan N, Narayanan M, de Souza RJ, van Dam RM. Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: a meta-analysis of clinical trials. Nutr J 2014; 13: 7.
[http://dx.doi.org/10.1186/1475-2891-13-7] [PMID: 24438170]
[140]
Elmhdwi MF, Elaali NMS, Mohamed NN, Muktar MA, Negia B. Anti-diabetic activity of methanolic extract of grape seeds in alloxan induced diabetic rats. Aust J Agric Res 2017; 6(5): 1-6.
[141]
Al-Ghamdi AAM, Shahat AA. Antioxidant, hypoglycemic and anti-diabetic activities of Ziziphus spina-christi (L) Willd (Rhamnacae) leaf extract. Trop J Pharm Res 2017; 16(11): 2601-10.
[http://dx.doi.org/10.4314/tjpr.v16i11.5]
[142]
Ghorbani A. Best herbs for managing diabetes: A review of clinical studies. Braz J Pharm Sci 2013; 49(3): 413-22.
[http://dx.doi.org/10.1590/S1984-82502013000300003]
[143]
Geberemeskel GA, Debebe YG, Nguse NA. Antidiabetic effect of fenugreek seed powder solution (Trigonella foenum-graecum l.) on hyperlipidemia in diabetic patients. J Diabetes Res 2019; •••20198507453
[http://dx.doi.org/10.1155/2019/8507453] [PMID: 31583253]
[144]
Verma N, Usman K, Patel N, et al. A multicenter clinical study to determine the efficacy of a novel fenugreek seed (Trigonella foenum-graecum) extract (Fenfuro™) in patients with type 2 diabetes. Food Nutr Res 2016; 60(1): 32382.
[http://dx.doi.org/10.3402/fnr.v60.32382] [PMID: 27733237]
[145]
Samani NB, Jokar A, Soveid M, Heydari M, Mosavat SH. Efficacy of the hydroalcoholic extract of Tribulus terrestris on the serum glucose and lipid profile of women with diabetes mellitus: A double-blind randomized placebo-controlled clinical trial. J Evid Based Complementary Altern Med 2016; 21(4): NP91-7.
[http://dx.doi.org/10.1177/2156587216650775] [PMID: 27255456]
[146]
Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res 2006; 20(12): 1036-9.
[http://dx.doi.org/10.1002/ptr.1988] [PMID: 17072885]