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DOI: 10.1055/a-1910-3505
A Systematic Review of the Potential Effects of Propolis Extracts on Experimentally-induced Diabetes

Abstract
Oxidative stress (OS) is involved in the development of diabetes mellitus (DM) and its complications. Thus, OS reduction may be an important strategy for DM therapy. Propolis is bee resins with high antioxidant activity and is used in the treatment of different diseases, including DM. Therefore, in this systematic review, we evaluated the impact of propolis administration in diabetic animals. We used the PRISMA strategy to collect preclinical studies published in English up to November 2021 in three databases (PubMed/Medline, Scopus, and Web of Science). We used the SYRCLE tool to analyze the risk of methodological bias. Our primary search returned 198 studies, of which 14 were considered eligible to be included in this review. The administration of propolis induced a hypoglycemic effect in the treated animals, which is probably due to the reduction of OS. The animals showed restoration of endogenous antioxidant defenses and reduced levels of markers for OS. The administration of propolis resulted in improvement in the lipid profile of treated animals. Our risk of bias assessment showed a methodological quality score of less than 30% due to a lack of randomization, blinding, and proper allocation of animals. Heterogeneity in treatments, lack of results, and use of non-standard extracts are limitations in our data analysis. Despite these limitations, propolis induced a significant hypoglycemic effect in diabetic animals when compared to untreated controls. This effect was associated with a reduction in OS, a process mediated by ROS neutralization and restoration of endogenous antioxidant defenses.
Supporting Information
- Supporting Information
The information taken from the studies is summarized in tables available in the Supporting Information.
Publication History
Received: 02 May 2022
Accepted after revision: 20 July 2022
Article published online:
28 September 2022
© 2022. Thieme. All rights reserved.
Georg Thieme Verlag KG
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References
- 1 World Health Organization. Diabetes. 2021 Accessed June 09, 2021 at: https://www.who.int/health-topics/diabetes%23tab=tab_1
- 2 International Diabetes Federation. IDF Diabetes Atlas 2021 10th. International Diabetes Federation 2021. Accessed December 19, 2021 at: https://diabetesatlas.org/atlas/tenth-edition/
- 3 Kharroubi AT, Darwish HM. Diabetes mellitus: The epidemic of the century. World J Diabetes 2015; 6: 850 DOI: 10.4239/wjd.v6.i6.850.
- 4 Deng L, Du C, Song P, Chen T, Rui S, Armstrong DG, Deng W. The role of oxidative stress and antioxidants in diabetic wound healing. Oxid Med Cell Longev 2021; 2021: 8852759 DOI: 10.1155/2021/8852759.
- 5 Luc K, Schramm-Luc A, Guzik TJ, Mikolajczyk TP. Oxidative stress and inflammatory markers in prediabetes and diabetes. J Physiol Pharmacol 2019; 70: 809-824 DOI: 10.26402/jpp.2019.6.01.
- 6 Newsholme P, Cruzat VF, Keane KN, Carlessi R, Bittencourt PIH. Molecular mechanisms of ROS production and oxidative stress in diabetes. Biochem J 2016; 473: 4527-4550 DOI: 10.1042/BCJ20160503C.
- 7 Kaneto H, Katakami N, Matsuhisa M, Matsuoka TA. Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis. Mediators Inflamm 2010; 2010: 453892 DOI: 10.1155/2010/453892.
- 8 Grabež M, Škrbić R, Stojiljković MP, Vučić V, Rudić Grujić V, Jakovljević V, Djuric DM, Suručić R, Šavikin K, Bigović D, Vasiljević N. A prospective, randomized, double-blind, placebo-controlled trial of polyphenols on the outcomes of inflammatory factors and oxidative stress in patients with type 2 diabetes mellitus. Rev Cardiovasc Med 2022; 23: 57 DOI: 10.31083/j.rcm2302057.
- 9 Domanico D, Fragiotta S, Cutini A, Carnevale C, Zompatori L, Vingolo E. Circulating levels of reactive oxygen species in patients with nonproliferative diabetic retinopathy and the influence of antioxidant supplementation: 6-Month follow-up. Indian J Ophthalmol 2015; 63: 9-14 DOI: 10.4103/0301-4738.151455.
- 10 Nna VU, Abu Bakar AB, Md Lazin MRML, Mohamed M. Antioxidant, anti-inflammatory and synergistic anti-hyperglycemic effects of Malaysian propolis and metformin in streptozotocin–induced diabetic rats. Food Chem Toxicol 2018; 120: 305-320 DOI: 10.1016/j.fct.2018.07.028.
- 11 Babu PVA, Liu D, Gilbert ER. Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J Nutr Biochem 2013; 24: 1777-1789 DOI: 10.1016/j.jnutbio.2013.06.003.
- 12 Kocot J, Kiełczykowska M, Luchowska-Kocot D, Kurzepa J, Musik I. Antioxidant potential of propolis, bee pollen, and royal jelly: Possible medical application. Oxid Med Cell Longev 2018; 2018: 7074209 DOI: 10.1155/2018/7074209.
- 13 Braakhuis A. Evidence on the health benefits of supplemental propolis. Nutrients 2019; 11: 2705 DOI: 10.3390/nu11112705.
- 14 Tiveron AP, Rosalen PL, Franchin M, Lacerda RCC, Bueno-Silva B, Benso B, Denny C, Ikegaki M, Alencar SM. Chemical characterization and antioxidant, antimicrobial, and anti-inflammatory activities of South Brazilian organic propolis. PLoS One 2016; 11: e0165588 DOI: 10.1371/journal.pone.0165588.
- 15 Silva BB, Rosalen PL, Cury JA, Ikegaki M, Souza VC, Esteves A, Alencar SM. Chemical composition and botanical origin of red propolis, a new type of Brazilian propolis. Evid Based Complement Alternat Med 2008; 5: 313-316 DOI: 10.1093/ecam/nem059.
- 16 Vieira de Morais D, Rosalen PL, Ikegaki M, Silva APS, Massarioli AP, Alencar SM. Active antioxidant phenolics from Brazilian red propolis: An optimization study for their recovery and identification by LC-ESI-QTOF-MS/MS. Antioxidants (Basel) 2021; 10: 297 DOI: 10.3390/antiox10020297.
- 17 Sforcin JM, Bankova V. Propolis: Is there a potential for the development of new drugs?. J Ethnopharmacol 2011; 133: 253-260 DOI: 10.1016/j.jep.2010.10.032.
- 18 Silva SS, Mizokami SS, Fanti JR, Miranda MM, Kawakami NY, Teixeira FH, Araújo EJA, Panis C, Watanabe MAE, Sforcin JM, Pavanelli WR, Verri WA, Felipe I, Conchon-Costa I. Propolis reduces Leishmania amazonensis-induced inflammation in the liver of BALB/c mice. Parasitol Res 2016; 115: 1557-1566 DOI: 10.1007/s00436-015-4890-4.
- 19 Nani BD, Sardi JCO, Lazarini JG, Silva DR, Massariolli AP, Cunha TM, de Alencar SM, Franchin M, Rosalen PL. Anti-inflammatory and anti-Candida effects of Brazilian organic propolis, a promising source of bioactive molecules and functional food. J Agric Food Chem 2020; 68: 2861-2871 DOI: 10.1021/acs.jafc.8b07304.
- 20 Hooijmans CR, Ritskes-Hoitinga M. Progress in using systematic reviews of animal studies to improve translational research. PLoS Med 2013; 10: e1001482 DOI: 10.1371/journal.pmed.1001482.
- 21 Pereira RM, Greco GMZ, Moreira AM, Chagas PF, Caldas IS, Gonçalves R, Novaes RD. Applicability of plant-based products in the treatment of Trypanosoma cruzi and Trypanosoma brucei infections: A systematic review of preclinical in vivo evidence. Parasitology 2017; 144: 1275-1287 DOI: 10.1017/S0031182017000634.
- 22 Yuan H, Ma Q, Ye L, Piao G. The traditional medicine and modern medicine from natural products. Molecules 2016; 21: 559 DOI: 10.3390/molecules21050559.
- 23 Moroole MA, Materechera SA, Mbeng WO, Aremu AO. Medicinal plants used for contraception in South Africa: A review. J Ethnopharmacol 2019; 235: 19-27 DOI: 10.1016/j.jep.2019.02.002.
- 24 Barré-Sinoussi F, Montagutelli X. Animal models are essential to biological research: Issues and perspectives. Future Sci OA 2015; 1: FSO63 DOI: 10.4155/fso.15.63.
- 25 King AJF. The use of animal models in diabetes research. Br J Pharmacol 2012; 166: 877-894 DOI: 10.1111/j.1476-5381.2012.01911.x.
- 26 Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiolog Res 2001; 50: 537-546
- 27 Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 2008; 51: 216-226 DOI: 10.1007/s00125-007-0886-7.
- 28 Thilakarathna SH, Vasantha Rupasinghe HP. Flavonoid bioavailability and attempts for bioavailability enhancement. Nutrients 2013; 5: 3367-3387 DOI: 10.3390/nu5093367.
- 29 Hu M. Commentary: Bioavailability of flavonoids and polyphenols: Call to arms. Mol Pharm 2007; 4: 803-806 DOI: 10.1021/mp7001363.
- 30 Cavalaro RI, Cruz RGD, Dupont S, de Moura Bell JMLN, Vieira TMFS. In vitro and in vivo antioxidant properties of bioactive compounds from green propolis obtained by ultrasound-assisted extraction. Food Chem X 2019; 4: 100054 DOI: 10.1016/j.fochx.2019.100054.
- 31 Park YK, Alencar SM, Aguiar CL. Botanical origin and chemical composition of Brazilian propolis. J Agric Food Chem 2002; 50: 2502-2506 DOI: 10.1021/jf011432b.
- 32 Cavalaro RI, Fabricio LFF, Vieira TMFS. Ultrasound-assisted extraction of antioxidants from Baccharis dracunculifolia and green propolis. Processes 2020; 8: 1530 DOI: 10.3390/pr8121530.
- 33 Bueno-Silva B, Marsola A, Ikegaki M, Alencar SM, Rosalen PL. The effect of seasons on Brazilian red propolis and its botanical source: chemical composition and antibacterial activity. Nat Prod Res 2017; 31: 1318-1324 DOI: 10.1080/14786419.2016.1239088.
- 34 Al-Ishaq RK, Abotaleb M, Kubatka P, Kajo K, Büsselberg D. Flavonoids and their anti-diabetic effects: Cellular mechanisms and effects to improve blood sugar levels. Biomolecules 2019; 9: 430 DOI: 10.3390/biom9090430.
- 35 El-Guendouz S, Aazza S, Lyoussi B, Majdoub N, Bankova V, Popova M, Raposo S, Antunes MD, Miguel MG. Effect of poplar-type propolis on oxidative stability and rheological properties of O/W emulsions. Saudi Pharm J 2018; 26: 1073-1082 DOI: 10.1016/j.jsps.2018.05.017.
- 36 Mahabaleshwarkar R, DeSantis A. Metformin dosage patterns in type 2 diabetes patients in a real-world setting in the United States. Diab Res Clin Pract 2021; 172: 108531 DOI: 10.1016/j.diabres.2020.108531.
- 37 Jové M, Mota-Martorell N, Pamplona R, Pradas I, Martín-Gari M, Ayala V. The advanced lipoxidation end-product malondialdehyde-lysine in aging and longevity. Antioxidants (Basel) 2020; 9: 1132 DOI: 10.3390/antiox9111132.
- 38 Czerska M, Mikołajewska K, Zieliński M, Gromadzińska J, Wąsowicz W. Todayʼs oxidative stress markers. Med Pr 2015; 66: 393-405 DOI: 10.13075/mp.5893.00137.
- 39 Hybertson BM, Gao B, Bose SK, McCord JM. Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation. Mol Aspects Med 2011; 32: 234-246 DOI: 10.1016/j.mam.2011.10.006.
- 40 Hotta S, Uchiyama S, Ichihara K. Brazilian red propolis extract enhances expression of antioxidant enzyme genes in vitro and in vivo . Biosci Biotechnol Biochem 2020; 84: 1820-1830 DOI: 10.1080/09168451.2020.1773756.
- 41 Haas MJ, Onstead-Haas LM, Szafran-Swietlik A, Kojanian H, Davis T, Armstrong P, Wong NCW, Mooradian AD. Induction of hepatic apolipoprotein A–I gene expression by the isoflavones quercetin and isoquercetrin. Life Sci 2014; 110: 8-14 DOI: 10.1016/j.lfs.2014.06.014.
- 42 Mulvihill EE, Allister EM, Sutherland BG, Telford DE, Sawyez CG, Edwards JY, Markle JM, Hegele RA, Huff MW. Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and hyperinsulinemia in LDL receptor-null mice with diet-induced insulin resistance. Diabetes 2009; 58: 2198-2210 DOI: 10.2337/db09-0634.
- 43 Kim YW, Byzova TV. Oxidative stress in angiogenesis and vascular disease. Blood 2014; 123: 625-631 DOI: 10.1182/blood-2013-09-512749.
- 44 Moldogazieva NT, Mokhosoev IM, Melʼnikova TI, Porozov YB, Terentiev AA. Oxidative stress and advanced lipoxidation and glycation end products (ALEs and AGEs) in aging and age-related diseases. Oxid Med Cell Longev 2019; 2019: 3085756 DOI: 10.1155/2019/3085756.
- 45 Lapchak PA, Zhang JH, Noble-Haeusslein LJ. RIGOR Guidelines: escalating STAIR and STEPS for effective translational research. Transl Stroke Res 2013; 4: 279-285 DOI: 10.1007/s12975-012-0209-2.
- 46 Landis SC, Amara SG, Asadullah K, Austin CP, Blumenstein R, Bradley EW, Crystal RG, Darnell RB, Ferrante RJ, Fillit H, Finkelstein R, Fisher M, Gendelman HE, Golub RM, Goudreau JL, Gross RA, Gubitz AK, Hesterlee SE, Howells DW, Huguenard J, Kelner K, Koroshetz W, Krainc D, Lazic SE, Levine MS, MacLeod MR, McCall JM, Iii RTM, Narasimhan K, Noble LJ, Perrin S, Porter JD, Steward O, Unger E, Utz U, Silberberg SD. A call for transparent reporting to optimize the predictive value of preclinical research. Nature 2012; 490: 187-191 DOI: 10.1038/nature11556.
- 47 Marques DVB, Felizardo AA, Souza RLM, Pereira AAC, Gonçalves RV, Novaes RD. Could diet composition modulate pathological outcomes in schistosomiasis mansoni? A systematic review of in vivo preclinical evidence. Parasitology 2018; 145: 1127-1136 DOI: 10.1017/S0031182018000057.
- 48 Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021; 372: n71 DOI: 10.1136/bmj.n71.
- 49 Bankova V. Chemical diversity of propolis and the problem of standardization. J Ethnopharmacol 2005; 100: 114-117 DOI: 10.1016/j.jep.2005.05.004.
- 50 Bankova V, Popova M, Trusheva B. Propolis volatile compounds: chemical diversity and biological activity: a review. Chem Cent J 2014; 8: 28 DOI: 10.1186/1752-153X-8-28.
- 51 Eriksen MB, Frandsen TF. The impact of PICO as a search strategy tool on literature search quality: A systematic review. J Med Libr Assoc 2018; 106: 420-431
- 52 Hooijmans CR, Rovers MM, Vries RBM, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLEʼs risk of bias tool for animal studies. BMC Med Res Methodol 2014; 14: 43 DOI: 10.1186/1471-2288-14-43.