January 10, 2007
Combined Use of Honey, Bee Propolis and Myrrh in Healing a Deep, Infected Wound in a Patient With Diabetes Mellitus
By Lotfy, M; Badra, G; Burham, W; Alenzi, F Q
Diabetes mellitus is a group of diseases characterised by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. Diabetes can be associated with serious complications including diabetic foot disease. Diabetic foot disease is estimated to affect 15% of people with diabetes.1Wound healing is a process that involves inflammation, proliferation/regeneration and finally remodeling. The normal orderly pattern is disrupted in chronic non-healing wounds, which are characterised by decreased levels of growth factors and increased protease activity. Wound healing is affected by serum albumin, tissue oxygenation, infection, hyperglycaemia, cytokines and proteases.2
A marker of non-healing wounds may be the prolonged presence of extracellular matrix molecules in the dermis.1 Other markers and potential mediators include increased levels of transforming growth factor (TGF)-β3,4 proteolytic factors such as matrix metalloproteinases,5 and the absence of IGF-I.6
Wound care includes a variety of approaches to enhance healing, with treatment of infection, vascular reconstruction, achieving adequate glycaemic control, removal of pressure, and ongoing wound debridement being important aspects of this care.2
A deep wound with tissue loss in the right foot of a 65-year-old male patient with diabetes mellitus was treated by a standard protocol that included strict control of blood sugar level. In addition, an antibiotic regimen was included to combat anaerobic and aerobic infection. Also, a paste consisting of myrrh, bee propolis and honey (MPH) was applied to the wound. Following treatment, the wound settled and healed well (Fig. 1).
The patient presented to the out-patient clinic of Minufiya University Hospital (MUH) with possible osteomyelitis. A foot wound showed severe oedema and the patient was unable to bear weight on the foot. On examination, the patient had a large abscess beneath the skin of the foot. An incision (3 cm) was made, pus was drained and the wound was cleaned. The patient returned home with antibiotic (gatifloxacin; 400 mg twice a day for five days) and an anti- inflammatory agent.
X-ray examination showed no bony abnormality and inflammation was prominent around the smallest toe. Two days later, the patient's foot was re-examined and debridement of the wound was performed to remove dead skin and necrotic tissue inside the opened cavity.
At all times during treatment, blood sugar level was controlled (in the range 150-170 mg/dL) using insulin. The patient was kept on metronidazole (1500 mg/day) and combined amoxicillin with clavulanic acid (1500 mg/day) for 10 days. Thereafter, ciprofloxacin (1500 mg/ day) was used instead of the combined amoxicillin with clavulanic acid. Pentoxifylline, vitacid calcium (vitamin C and calcium carbonate) and vitazinc (vitamins A and E plus zinc) were added to the treatment regimen to aid vascularity and healing. From the beginning of treatment until the deep wound healed, the patient was maintained on an oral dose of bee propolis (400 mg/day). Erythrocyte sedimentation rate (a good indicator of treatment efficacy) was 125 mm prior to treatment and dropped to 65 mm after two weeks and 25 mm after four weeks, where it stabilised.
The most significant results were obtained during the use of the MPH paste (800 mg bee propolis, 50 g myrrh, mixed together in honey). The paste was prepared every three days and stored in a refrigerator. Wound cleaning was performed daily using standard methods in addition to the MPH paste to fill the wound cavity. The effectiveness of the paste in keeping the wound clean was indicated by a complete absence of pus and cellular exudate. After four weeks the wound had healed well and the patient returned to work.
Poor wound healing in people with diabetes is well recognised.7 However, there is little information about many aspects of foot care in people with diabetes, including wound healing.8 The American Diabetes Association9 suggests a range of predisposing factors to explain poor healing of wounds in people with diabetes, including abnormal cellular and/or inflammatory pathways, peripheral neuropathy and vascular disease and/or tissue hypoxia. Abnormal cellular function, particularly in fibroblasts and neutrophils, has been found in people with diabetes. In vitro, hyperglycaemia may be toxic to these cellular elements, while in vivo it may result in a greater susceptibility to infection.
Modest differences in the function of neutrophils, macrophages and fibroblasts associated with hyperglycaemia have been postulated, but these have not been demonstrated conclusively in vivo. Advanced glycosylation end products accumulate in diabetes as a result of hyperglycaemia, leading to the non-enzymatic glycosylation of collagen.10 This process results in the production of abnormal collagen, which is highly inflexible and prone to breakdown, particularly over pressure areas.11
In this report, a paste is described that keeps a wound clean, which is especially important in cases that involve tissue loss. The MPH paste contains safe and effective components that have prominent antimicrobial activity.
Myrrh is an oleogum resin obtained from the stem of the plant Commiphora molmol. It is a safe, natural flavouring substance approved by the US Food and Drug Administration.12,13 In experimental studies on Swiss albino mice, myrrh from C. molmol exhibited no mutagenicity and proved to be a potent cytotoxic drug against Ehrlich solid tumour cells. The antitumour potential of C. molmol was comparable with that of the standard cytotoxic drug cyclophosphamide.14 Studies with animal and human models demonstrate antischistosomal and other antiparasitic activity for myrrh and have found it to be safe and effective.15,16
Myrrh has considerable antimicrobial activity and is used in a variety of diseases.17 It has antibacterial and antifungal activity against standard pathogenic strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans.18 In addition, it has an antidiabetic effect, especially in non-insulin-dependent diabetes mellitus (NIDDM).19 Moreover, Myrrh has found pharmacological application in the reduction of cholesterol and triglycerides.20
Propolis is a resinous substance collected from trees by the bee Apis mellifera, which uses it as a building and insulating material in the hive. It is known that propolis has antimicrobial, antioxidative, anti-ulcer and antitumour, anti-inflammatory, hypotensive and immune stimulatory activities.21
Antimicrobial activity has been observed against S. aureus,22,23 Streptococcus pyogenes,24 Gram-positive and Gram-negative bacterial species and Candida species,25,26 S. mutons,27 anaerobic bacteria in the human oral cavity,28 salmonellas,29 and other microorganisms including mycobacteria.30 Antibacterial activity of propolis against Staphylococcus aureus is higher when extracts are prepared in 60- 80% ethanol.22 In vitro synergy between propolis and antimicrobial drugs has been investigated,31,32 and preparations combining propolis with antibiotic and antifungal agents are of potential medical interest.26
Honey is an ancient remedy that has regained popularity as an alternative treatment for antibiotic-resistant bacteria. Both honey and sugar pastes are considered useful as topical antimicrobial agents, mainly because of their high osmolarity and the ability to minimise water availability to bacteria.33 Although the dilution of honey by wound fluid is likely to reduce the efficacy of its osmotic effect, the slow and sustained production of hydrogen peroxide by some types of honey (e.g., manuka honey) is capable of maintaining an antimicrobial effect at a concentration approximately 1000-fold higher than that used commonly in antiseptic solutions (i.e., 3%).33 Also, certain components of manuka honey (e.g., flavonoids and aromatic acids) demonstrate antimicrobial properties.33
Honey is also an effective wound deodorant, an effect attributed to the presence of glucose, which is metabolised by bacteria in preference to proteinaceous necrotic tissue, resulting in the production of lactic acid and not the malodorous compounds generated by protein degradation.33 In addition, the observed benefits of honey in infected wounds may be attributed to the high glucose content and low pH, both of which stimulate macrophages.34
In the present case study, application of MPH resulted in a clean and odour-free wound, which healed well. However, the results of this single case need to be confirmed in a study of a larger number of patients. In the meantime, use of the MPH paste would appear to reduce the cost of deep wound treatment and improve the outcome in the patients affected.
1 Mancini L, Ruotolo V The diabetic foot: epidemiology. Rays 1997; 22: 511-23.
2 Bloomgarden ZT. Diabetes complications. Diabetes Care 2004; 27: 1506-14.
3 Loots MA, Lamme EN, Zeegelaar J, Mekkes JR, Bos JD, Middelkoop E. Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. J Invest Dermatol 1998; 111: 850-7.
4 Jude EB, Blakytny R, Bulmer J, Boulton AJ, Ferguson MW. Transforming growth factor-beta 1, 2, 3 and receptor type I and II in diabetic foot ulcers. Diabet Med 20\02; 19: 440-7.
5 Lobmann R, Ambrosch A, Schultz G, Waldmann K, Schiweck S, Lehnert H. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients. Diabetologia 2002; 45:1011-6.
6 Blakytny R, Jude EB, Martin Gibson J, Boulton AJ, Ferguson MW. Lack of insulin-like growth factor 1 (IGF1) in the basal keratinocyte layer of diabetic skin and diabetic foot ulcers. J Pathol 2000; 190: 589-94.
7 Bouter KP, Storm AJ, de Groot RRM et al. The diabetic foot in Dutch hospitals: epidemiological features and clinical outcome. Eur J Med 1993; 2: 215-8.
8 Pecoraro RE, Ahroni JH, Bpyko EJ et al. Chronology and extremities of tissue repair in diabetic lower-extremity ulcers. Diabetes 1991; 40:1305-13.
9 American Diabetes Association. Consensus development conference on diabetic foot wound care. Diabetes Care 1991; 22: 1354-60.
10 McInnes A. Guide to the assessment and management of diabetic foot wounds. The Diabetic Foot 200; 4 (Suppl 1): SI-II.
11 Ikes RS, Wolfe JHN. The diabetic foot. BMJ 1991; 303: 1053-5.
12 Hall BL, Oser BL. Recent progress in the consideration of flavoring ingredients under the food additive amendment. 3. GRAF substances. Food Tcchnol 1965; 19: 151-97.
13 Ford RA, Api AM, Letizia CS. Monographs on fragrance to raw materials. Food Chem Toxicol 1992; 30 (Suppl): 91S-92S.
14 Al Harbi MM, Qureshi S, Ahmed MM, Rafatulla S, Shah AH. Effect of Commiphora molmol (oleogum resin) on the cytological and biochemical changes induced by cyclophosphamide in mice. Am J Chin Med 1994; 22: 77-82.
15 Botros S, Sayed H, El-Dusoki H et al. Efficacy of Mirazid in comparison with praziquantel in Egyptian Schistosoma mansoniinfected school children and households. Am J Trop Med Hyg 2005; 72 (2): 119- 23.
16 Sheir Z, Nasr AA, Massoud A et al. A safe, effective, herbal antischistosomal therapy derived from myrrh. Am J Trop Med Hyg 2001; 65: 700-4.
17 El Ashry ES, Rashed N, Salama OM, Saleh A. Components, therapeutic value and uses of myrrh. Pharmazie 2003; 58 (3): 163-8.
18 Dolara P, Corte B, Ghelardini C et al. A. Local anaesthetic, antibacterial and antifungal properties of sesquiterpenes from myrrh. Planta Med 2000; 66 (4): 356-8.
19 Al-Awadi F, Fatania H, Shamte U. The effect of a plant mixture extract on liver gluconeogenesis in streptozotocin induced diabetic rats. Diabetes Res 1991; 18 (4):163-8.
20 Michie CA, Cooper E. Frankincense and myrrh as remedies in children. J R Soc Med. 1991; 84: 602-5.
21 Lotfy M. Biological activity of bee propolis in health and disease. Asian Pac J Cancer Prev 2006; 7: 22-31.
22 Fernandes Junior A, Balestrin ECC, Cunha MLRS. Anti- Staphylococcus aureus activity of bee propolis extracts prepared with different ethanol concentrations. Rev Cinc Farm 2003; 24: 147- 52.
23 Fernandes Junior A, Leomil L, Fernandes AAH, Sforcin JM. The antibacterial activity of propolis produced by Apis mellifera L. and Brazilian stingless bees. J Venom Anim Toxins 2001; 7: 173-82.
24 Bosio K, Avanzini C, D'avolio A, Ozimo O, Savoia D. In vitro activity of propolis against Streptococcus pyogenes. Lett Appl Microbiol 2000; 31:174-7.
25 Drago I, Mombelli B, De Vecchi E, Fassina MC, Tocalli L, Gismondo MR. In vitro antimicrobial activity of propolis dry extract. J Chemotherapy 2002; 12: 390-5.
26 Stepanovic S, Antic N, Dakic I, Svabic-Vlahovic M. In vitro antimicrobial activity of propolis and synergism between propolis and antimicrobial drugs. Microbiol Res 2003; 158: 353-7.
27 Koo H, Rosalen PL, Cury JA, Park YK, Bowen WH. Effects of compounds found in propolis on Streptococcus mutans growth and on glucosiltransferase activity. Antimicrob Agents Chemother 2002; 46:1302-9.
28 Santos FA, Bastos EMA, Uzeda B, Carvalho MAR, Farias ESA, Braga FC. Antibacterial activity of Brazilian propolis and fractions against oral anaerobic bacteria. J Ethnopharmacol 2002; 80: 1-7.
29 Orsi RO, Sforcin JM, Rail VLM, Funari SRC, Barbosa L, Fernandes Junior A. Susceptibility profile of Salmonella against the antibacterial activity of propolis produced in two regions of Brazil. J Venom Anim Toxins 2005; 11:109-16.
30 Banskota AH, Tezuka Y, Kadota S. Recent progress in pharmacological research of propolis. Phytother Res 2001; 15: 561- 71.
31 Scheller S, Dworniczak S, Waldemar KK, Rajca M, Tomczik A, Shani J. Synergism between ethanolic extract of propolis (EEP) and anti-tuberculosis drugs on growth of mycobacteria. Z Naturforsch C 1999; 54: 549-53.
32 Fernandes Junior A, Balestrin EC, Betoni JEC, Orsi RO, Cunha MLRS, Montelli AC. Propolis: anti-Staphylococcus aureus activity and synergism with antimicrobial drugs. Mem Inst Oswaldo Cruz, Rio de Janeiro 2005; 100: 563-6.
33 Molan PC. The role of honey in the management of wounds. J Wound Care 1999; 8: 415-8.
34 Cooper RA, Molan PC. Honey in wound care. J Wound Care 1999; 8:340.
M. LOTFY*, G. BADRA[dagger], W. BURHAM[double dagger] and F. Q. ALENZI
* Biunmiicnl Research Unit, Molecular and Cellular Biology Department, Genetic Engineering and Biotechnologif Research Institute, Minufiya University, Sadat City; [dagger] Department of Hepatohgif and Internal Medicine, National Liver Institute, Minnfiya University, Minufiya; [double dagger] Department of Surgery, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Department of Medical Laboratories, College of Applied Medical Sciences, King Faisal University, Dammam, Saudi Arabia
Correspondence to: Dr Mahmoud Lotfy
Molecular and Cellular Biology Department, Genetic Engineering and Biotechnology
Research Institute, Minufiya University, Sadat City, PO 79, Minnfiya, Egypt
Email: [email protected]
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