Comparison of stingless bee honey and silver sulfadiazine on diabetic wound healing in rat models

Authors

  • Nanang Miftah Fajari Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Indonesia
  • Agung Pranoto Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Hospital, Surabaya, Indonesia
  • David Sontani Perdanakusuma Department of Plastic Reconstructive and Aesthetic Surgery, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Hospital, Surabaya, Indonesia
  • Muhammad Darwin Prenggono Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitas Lambung Mangkurat, Ulin Hospital, Banjarmasin, Indonesia
  • Mohammad Rudiansyah Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitas Lambung Mangkurat, Ulin Hospital, Banjarmasin, Indonesia
  • Hendra Wana Nur'amin Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitas Lambung Mangkurat, Ulin Hospital, Banjarmasin, Indonesia; Department of Pharmacology, Faculty of Medicine and Health Sciences, Universitas Lambung Mangkurat, Banjarmasin, Indonesia
  • Yulia Syarifa Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitas Lambung Mangkurat, Ulin Hospital, Banjarmasin, Indonesia
  • Nuvita Hasrianti Internal Medicine Residency Program, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitas Lambung Mangkurat, Ulin Hospital, Banjarmasin, Indonesia
  • Imelda Nita Saputri Internal Medicine Residency Program, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitas Lambung Mangkurat, Ulin Hospital, Banjarmasin, Indonesia
  • Muhammad Irawan Afrianto Internal Medicine Residency Program, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitas Lambung Mangkurat, Ulin Hospital, Banjarmasin, Indonesia
  • Annisa Halida Husna Internal Medicine Residency Program, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitas Lambung Mangkurat, Ulin Hospital, Banjarmasin, Indonesia

DOI:

https://doi.org/10.13181/mji.oa.257974

Keywords:

diabetic foot, honey, silver sulfadiazine, wound healing

Abstract

BACKGROUND Diabetic foot ulcers (DFUs) are a major health concern in Indonesia. Adjuvant therapies may improve healing by avoiding secondary infections, promoting angiogenesis, and supporting oxygen circulation. This aimed to evaluate the effect of stingless bee honey (SBH) from Heterotrigona itama on diabetic wound size in rats (Rattus norvegicus), compared to silver sulfadiazine (SSD).

METHODS An experimental study was conducted on 13 diabetic wounds in streptozotocin-induced diabetic rats treated with three types of therapies: SSD (n = 5), pure SBH (n = 5), and SBH with 20% water content (n = 3). The study initially involved 21 rats, but eight died during the diabetes modeling and wound observation phases, presumably due to hyperglycemia. Baseline characteristics did not differ significantly across the groups.

RESULTS SBH with 20% water content and pure SBH reduced wound size by 95.1% and 92.1%, outperforming SSD (77.4%), with all therapies showing statistically significant improvement (p<0.05). However, the differences between groups were not statistically significant (p = 0.162).

CONCLUSIONS Topically applied SBH is a potential natural therapeutic agent for diabetic wounds, in addition to standard treatment such as SSD.

Downloads

Download data is not yet available.

References

Abbas ZG. Reducing diabetic limb amputations in developing countries. Expert Rev Endocrinol Metab. 2015;10(4):425-34. https://doi.org/10.1586/17446651.2015.1058151

Pemayun TGD, Naibaho RM. Clinical profile and outcome of diabetic foot ulcer, a view from tertiary care hospital in Semarang, Indonesia. Diabet Foot Ankle. 2017;8(1):1312974. https://doi.org/10.1080/2000625X.2017.1312974

Akkus G, Sert M. Diabetic foot ulcers: a devastating complication of diabetes mellitus continues non-stop in spite of new medical treatment modalities. World J Diabetes. 2022;13(12):1106-21. https://doi.org/10.4239/wjd.v13.i12.1106

Daryago AAA, Fitriani F, Kartowigno S, Aryani IA, Yahya YF, Diba S, et al. Management of diabetic foot ulcers: dermatology perspective. Bali Dermatol Venereol J. 2021;4(2). https://doi.org/10.15562/bdv.v4i2.65

Schaper NC, van Netten JJ, Apelqvist J, Bus SA, Hinchliffe RJ, Lipsky BA; IWGDF Editorial Board. Practical guidelines on the prevention and management of diabetic foot disease (IWGDF 2019 update). Diabetes Metab Res Rev. 2020;36 Suppl 1:e3266. https://doi.org/10.1002/dmrr.3266

Benbow M. Best practice in wound assessment. Nursing Standard. 2016;30(27):40-7. https://doi.org/10.7748/ns.30.27.40.s45

Alam F, Islam MA, Gan SH, Khalil MI. Honey: a potential therapeutic agent for managing diabetic wounds. Evid Based Complement Alternat Med. 2014;2014:169130. https://doi.org/10.1155/2014/169130

Brudzynski K. A current perspective on hydrogen peroxide production in honey. A review. Food Chem. 2020;332:127229. https://doi.org/10.1016/j.foodchem.2020.127229

Ewnetu Y, Lemma W, Birhane N. Antibacterial effects of Apis mellifera and stingless bees honeys on susceptible and resistant strains of Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae in Gondar, Northwest Ethiopia. BMC Complement Altern Med. 2013;13:269. https://doi.org/10.1186/1472-6882-13-269

Di Domenico EG, De Angelis B, Cavallo I, Sivori F, Orlandi F, Fernandes Lopes Morais D'Autilio M, et al. Silver sulfadiazine eradicates antibiotic-tolerant Staphylococcus aureus and Pseudomonas aeruginosa biofilms in patients with infected diabetic foot ulcers. J Clin Med. 2020;9(12):3807. https://doi.org/10.3390/jcm9123807

Charan J, Kantharia ND. How to calculate sample size in animal studies? J Pharmacol Pharmacother. 2013;4(4):303-6. https://doi.org/10.4103/0976-500X.119726

Agbagwa OE, Ekeke C, Israel PC. Antibacterial efficacy and healing potential of honey from different zones in Nigeria on diabetic-induced wound infection in wistar rats. Int J Microbiol. 2022;2022:5308435. https://doi.org/10.1155/2022/5308435

Zulkhairi Amin FA, Sabri S, Mohammad SM, Ismail M, Chan KW, Ismail N, et al. Therapeutic properties of stingless bee honey in comparison with European bee honey. Adv Pharmacol Sci. 2018;2018:6179596. https://doi.org/10.1155/2018/6179596

Bogdanov S. Honey in medicine: a review [Internet]. 2017 [cited date]. Available from: www.apitherapy.com.

Misrahanum, Aqilah H, Murniana. Quality analysis, phenolic and flavonoid content, and antimicrobial activity of stingless bees honey (Heterotrigona itama). Pharm J Indones. 2023;20(02):150-6. https://doi.org/10.30595/pharmacy.v0i0.17205

Ng WJ, Sit NW, Ooi PAC, Ee KY, Lim TM. The antibacterial potential of honeydew honey produced by stingless bee (Heterotrigona itama) against antibiotic resistant bacteria. Antibiotics. 2020;9(12):871. https://doi.org/10.3390/antibiotics9120871

Sadeghpour Heravi F, Zakrzewski M, Vickery K, G. Armstrong D, Hu H. Bacterial diversity of diabetic foot ulcers: current status and future prospectives. J Clin Med. 2019;8(11):1935. https://doi.org/10.3390/jcm8111935

Sharp A, Clark J. Diabetes and its effects on wound healing. Nurs Stand. 2011;25(45):41-7. https://doi.org/10.7748/ns2011.07.25.45.41.c8626

Al-Hatamleh MAI, Boer JC, Wilson KL, Plebanski M, Mohamud R, Mustafa MZ. Antioxidant-based medicinal properties of stingless bee products: recent progress and future directions. Biomolecules. 2020;10(6):923. https://doi.org/10.3390/biom10060923

Goulding V. The effects of diabetes on collagen within wound healing. The Diabetic Foot Journal. 2015;18(2):75-80.

Oropallo AR, Serena TE, Armstrong DG, Niederauer MQ. Molecular biomarkers of oxygen therapy in patients with diabetic foot ulcers. Biomolecules. 2021;11(7). https://doi.org/10.3390/biom11070925

Halwany W, Hakim SS, Rahmanto B, Wahyuningtyas RS, Siswadi, Andriani S, et al. A simple reducing water content technique for stingless bee honey (Heterotrigona itama) in South Kalimantan. In: IOP Conference Series: Materials Science and Engineering. International Conference on Forest Products (ICFP) 2020: 2th International Symposium of IWORS; 2020 Sep 1; Bogor, Indonesia. Bristol: IOP Publishing Ltd; 2020. https://doi.org/10.1088/1757-899X/935/1/012011

Codex Alimentarius Commission. Codex standard for honey: CODEX STAN 12-1981 [Internet]. Codex Alimentarius Commission; 2001 [cited date]. Available from: https://www.fao.org/fao-who-codexalimentarius.

Saputra SH, Saragih B, Kusuma I, Tangke Arung E. The physicochemistry of stingless bees honey (Heterotrigona itama) from different meliponiculure areas in East Kalimantan, Indonesia. In: Proceedings of the Joint Symposium on Tropical Studies (JSTS-19); 2019 Sep 4-6. Berau, Indonesia. Paris: Atlantis press; 2021. p. 329-36. https://doi.org/10.2991/absr.k.210408.056

Ali A. Effective dose of streptozotocin for induction of diabetes mellitus and associated mortality rate in Wistar albino rats. Pakistan J Med Dent. 2019;8(04):50-4. https://doi.org/10.36283/PJMD8-4/009

Katsuhiro M, Hui Teoh S, Yamashiro H, Shinohara M, Fatchiyah F, Ohta T, et al. Effects on glycemic control in impaired wound healing in spontaneously diabetic torii (SDT) fatty rats. Med Arch. 2018;72(1):4-8. https://doi.org/10.5455/medarh.2018.72.4-8

Dasari N, Jiang A, Skochdopole A, Chung J, Reece EM, Vorstenbosch J, et al. Updates in diabetic wound healing, inflammation, and scarring. Semin Plast Surg. 2021;35(03):153-8. https://doi.org/10.1055/s-0041-1731460

Eteraf-Oskouei T, Najafi M. Traditional and modern uses of natural honey in human diseases: a review. Iran J Basic Med Sci. 2013;16(6):731-42.

Oaks RJ, Cindass R. Silver Sulfadiazine. 2023 Jan 22. In: StatPearls [Internet]. Treasure Island: StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556054/.

Published

2025-09-30

How to Cite

1.
Fajari NM, Pranoto A, Perdanakusuma DS, Prenggono MD, Rudiansyah M, Nur’amin HW, et al. Comparison of stingless bee honey and silver sulfadiazine on diabetic wound healing in rat models. Med J Indones [Internet]. 2025 Sep. 30 [cited 2025 Oct. 9];34(3):151-7. Available from: https://mji.ui.ac.id/journal/index.php/mji/article/view/7974

Issue

Section

Basic Medical Research

Most read articles by the same author(s)