Both honeybees (Apis spp.) and Melipona Stingless Bees (Trigona spp.) produce honeys with high nutritional and therapeutics value. Until recently, the information regarding potential health benefits of Stingless Bee Honey (SBH) in medical databases is still scarce as compared to the common European bee honey (EBH) which is well known for their properties as therapeutic agents. Although there have been very few reports on SBH, empirically these products would have similar therapeutic quality as the EBH. In addition, due to the structure of the nest, few studies reported that the antimicrobial activity of SBH is a little bit stronger than EBH.
Therefore, the composition of both the types of honey as well as the traditional uses and clinical applications were compared. The results of various studies on EBH and SBH from tissue culture research to randomised control clinical trials were collated in this review. Interestingly, there are many therapeutic properties that are unique to SBH. Therefore, Stingless Bee Honey (SBH) has a great potential to be developed for modern medicinal uses.
Honey is an important natural food product since ancient times and is known for its nutritional and therapeutic values. It is produced from liquid plant exudates which is gathered, modified, and stored by different types of bees. Among all, European honeybees (Apis mellifera) and Melipona Stingless Bees are the two most common bees. The European honey bee is a member of a group of bees in the genus of Apis whereas Stingless Bee can be classified into two genera, namely, the Melipona and the Trigona. Both have important role in flower pollination.
Honey produced by stingless bees is known with various names such as Meliponine honey, stingless bee honey (SBH) pot-honey, and also Melipona honey (in Mayan areas). It is one of the valuable bee products and is attributed with some medicinal properties by ancient peoples. Since the 20th century, various studies on the chemical and biological properties of honey had been conducted due to their extraordinary antibacterial, bacteriostatic, anti-inflammatory, wound, and sunburn healing effects.
Honey is one of the outstanding sources of energy due to its high sugar concentration. The energy input represented by honey is approximately 300 kcal per 100 g. The high calorific value of honey makes it suitable for athletes as it contains readily absorbed glucose which will be converted into energy in a short time. Other than it is used as a source of energy, honey is also important for bones and teeth. It helps in absorption of calcium and magnesium retention which may contribute to stronger bone and better dental calcification. This is due to the presence of nondigestable carbohydrate such as raffinose that produces short-chain fatty acid (SCFA) as the by-product from the fermentation process in the caecum and colon. The SCFA helps to lower the intestinal pH and creating a favourable environment that increases mineral such as calcium solubility and absorption.
Polyphenols of Stingless Bee Honey and European Bee Honey
Flavonoids and phenolic acids are the most common group of polyphenols that are previously detected in both honeys. As for the flavonoid groups, only the flavonols (such as myricetin, kaempferol, 8-methoxy kaempferol, quercetin, isorhamnetin, quercetin-3-methyl ether, quercetin-3, 7-dimethyl ether, pinobanksin, rutin, and galangin), flavones (such as genkwanin, luteolin, apigenin, tricetin, and chrysin), and flavanones (such as pinocembrin and pinostrobin) were previously detected in honey. Meanwhile, among the phenolic acid group, the hydroxybenzoic acids such as methyl syringate, gallic acid, syringic acid, benzoic acid, and 4-hydroxybenzoic acid and hydroxyl-cinnamic acids such as chlorogenic, vanillic, caffeic, p-coumaric, and ferulic acids are present in various honey samples.
Honey is known for its antioxidant activity. A prior investigation indicated that the total antioxidant activity of honey is primarily provided by its phenolic composition, rather than vitamin C and other components. The antioxidants that occur naturally in honey are flavonoids, phenolic acids, enzymes (e.g., glucose oxidase and catalase), ascorbic acid, carotenoid-like substances, organic acids, Maillard reaction products, amino acids, and proteins Several in vivo studies strongly suggested that long-term consumption of diets rich in these types of polyphenols significantly ameliorates the adverse effects of several liver-, heart-, kidney-, brain-, and pancreas-associated diseases as well as those of genetic disorders such as tumors and cancer.
Traditional Uses of Stingless Bee Honey and European Bee Honey
Natural honey has been used to prevent and treat variety of ailments since years ago. For example, newborn babies were fed with EBH as a supplement, meanwhile EBH also has been used by Ayurvedic physicians as alternatives for medicines, and it was recommended to satisfy the immediate calorie demand for the patients.
According to the natives, after being extracted, the honey is often consumed along with a hot drink, or even alone. As medication, Stingless Bee Honey (SBH) is employed for treating various sicknesses by combining this honey with different ingredients such as lemon, agave mezcal, and pulp of Crescentia alata. The combination was used to treat cold, cough, and respiratory illness such as bronchitis. Besides that, the SBH is extensively used as a fundamental part of medicine by the Maya traditional doctors as remedy for high fever, treatment for wounds and burns, and also the cure for poisonous stings. Despite being known as functional food, Melipona honey is also credited with many therapeutic values.
Therapeutic Effects of Stingless Bee Honey and European Bee Honey and Their Polyphenols
Microbial resistance towards modern antimicrobial drugs is rising and had become the topic of interest among the scientists in which scientists are developing novel drugs with less or no microbial resistance, and also have broad-spectrum inhibition activity. Despite the traditional uses of honey as therapeutic agents, honey is recently acknowledged in modern medicine development due to its valuable nutritional quality. It also portrays potential properties against reactive oxygen species (ROS), acts effectively as anti-inflammatory and antibacterial agents against bacteria and fungi and a potential substitute in reducing coughs and wound curing.
The common therapeutic properties of most honeys are more likely based on their floral origins. Since few years back, the role of honey in wound healing has been widely studied and proven to be the most effective therapeutic effects of honey. Previously, honey has been used to treat wound infection and promotes wound healing by the Russians during World War 1. Mixture of honey and cod liver oil has shown to be effective by the Germans, in treating ulcers and burns. In addition, honey is world widely known for its roles in the treating of famous ophthalmological diseases such as keratitis, conjunctivitis, corneal injuries, blepharitis, and chemical and thermal burns to eyes.
Raw Honey contains various polyphenols, which differs according to the origin and bee species. Various polyphenols, of which some are also detected in honey, have been proven to curb the development of many diseases. They perform this action via several specific mechanisms such as regulation of a specific gene expression or altering metabolic pathways by means of promoting or blocking specific pathways. However, differences in honey samples may affect the type of polyphenols found in honey. As one type of honey might not contain all of the polyphenols described and the protective effects of polyphenols are varied, it is advisable to consume variety of honey samples. The therapeutics effects of SBH and EBH such as antidiabetic, wound healing, anticancer, treatment of eye disease, and effects of fertility as proven by many scientific studies will be described as below.
Honey and other medicinal plants which are reported to contain many bioactive compounds were used traditionally and are still being used as alternative to treat diabetes. Evidences from scientific studies showed that dietary polyphenols are useful in treatment of diabetes mellitus. Out of many polyphenols found in both honeys, only few of them, such as quercetin, apigenin, luteolin, catechin, rutin, and kaempferol, are detected to exhibit antidiabetic properties. This is achieved via several mechanisms to reduce blood glucose levels. These include several important mechanisms such as α-amylase and α-glucosidase and gluconeogenic enzymes inhibition, enhancement of pancreatic b-cell protection and glucose uptake, and reduction of oxidative stress.
Honey therapy has been used to treat septic wounds, surgical wound, or wounds of abdominal wall and perineum due to its excellent wound healing properties. Previously, it is also being used in treating abrasion, amputation, and burns. In general, the oedema, inflammation, and exudation that commonly occur in all types of wounds were reduced by honey in order to improve the wound healing effects. The growth of epithelial cells and fibroblasts was also stimulated by honey.
A few in vitro studies revealed the substantial antimicrobial activity of SBH, which could also suggests the possible wound healing activity of this honey. In addition, combination of SBH and other substances such as antibiotic ampicillin or garlic extract, rather than these substances alone, showed more effective effects in inhibiting the growth of S. aureus, which is the most common pathogenic bacteria causing wound infection. Honey is useful as wound dressing as it helps to stimulate the healing process and can clear the infection quickly for it portrays better cleansing activity. Besides, it has proven anti-inflammatory activity and plays a great role in stimulating tissue regeneration.
Honey, as described by many scientific evidences, may be considered as a great chemopreventive agent. Chemoprevention may be described as the usage of natural or synthetic compounds in order to decrease the risk of cancer development.
Scientific evidence has proven that superoxide anion radical and inflammation can cause somatic mutation which will eventually evolve to initiate cancer. Due to its excellent anti-inflammatory activity, the anticancer effect of honey was also being investigated. According to Ahmed and Othman, as Melipona honey is known with its apoptotic, antiproliferative, antioxidant, anti-inflammatory, estrogenic, and immunomodulatory activity, these might be considered as the possible mechanisms of how honey prevent the progress of the cancer formation.
Meanwhile, SBH, which is also known for its antioxidant activity, prevents the induction of colon cancer by azoxymethane (AOM) in rats. Aberrant crypt foci (ACF) act as a biomarker in identifying the colon cancer development. To observe the effect of SBH on ACF, SBH was administered orally (1183 mg/kg body weight) and had proven to reduce the total number of ACF and aberrant crypt and crypt multiplicity. Therefore, SBH is neither harmful nor toxic to the animal. An in vitro study was also conducted to screen for the cytotoxic activity of different stingless bee products against five human cancer cell line, namely, BT474 (ductal carcinoma and lung undifferentiated cancer), HepG29 (liver hepatoblastoma), KatoIII (gastric carcinoma), and SW620 (adenocarcinoma), whereby the crude extracts of SBH showed great cytotoxicity effects towards HepG2 cell line, while propolis crude extracts exhibit high cytotoxicity effects towards all the human cancer cell line.
Polyphenols with anticancer effects that can be found in both honeys are quercetin, apigenin, chrysin, and luteolin. The mechanisms that are involved in cancer prevention by these polyphenols include inhibition of cell proliferation, modulation of cancer signalling pathways, and induction of tumor cell apoptosis. Uncontrolled cell proliferation had caused the cancer cells to increase at a faster rate; therefore, if the uncontrolled cell proliferation can be inhibited or reduced, cancer prevention is more likely to be successful. Polyphenols, which are also known for their antioxidant properties, are very helpful in preventing cell proliferation. For example, chrysin which is an important honey flavone helps to control the cell proliferation by activating p38-MAPK via accumulation of p21Wafi/Cip1 in C6 glioma cells of rats. Meanwhile, apigenin prevents proliferation of pancreatic cell as it helps to reduce levels of cyclin A, cyclin B, and the phosphorylated forms of cdc2 and cdc25, thereby arresting the G2/M phase of the cell cycle.
Treatment for Ocular Diseases
A study demonstrated that the bacterial flora in the conjunctival sac of patients with cataract and scheduled for vitrectomy was successfully eradicated after continuous administration of 25% sterile honeydew honey (EBH) for 7 days. Similarly, Albietz and Lenton pointed to the fact that the EBH significantly reduced formation of the whole colony-forming units in the eyelids and conjunctivae in patients with dry eye syndrome after one and three months of therapy.
Recently, Bashkaran et al. compared the anti-inflammatory and antioxidant effect of the EBH with a corticosteroid preparation (prednisone) in the treatment of alkali burn in rabbit eyes and confirmed the anti-inflammatory effects of this honey on experimental animals, with no significant difference between the two treatments. In a clinical study, in which 16 patients with oedema of the corneal epithelium who had not been indicated for a surgical procedure were subjected to local therapy with the EBH.
The result indicated that all corneas manifested an immediate regression of the corneal oedema with EBH treatment. Previously, a preliminary study was conducted by Vit, where SBH Melipona drop honey was applied on selenite-induced rats and had resulted in reducing the rate of the cataract progress, in 20% of the rats in the group that received honey for the opacification treatment. Despite that, SBH was also proven to reduce the infection time for eye diseases caused by Staphylococcus aureus and Pseudomonas aeruginosa, via in vivo studies using rabbit as the animal model.
Polyphenols inhibit the angiogenesis and inflammatory cytokines and also eye diseases by suppressing formation of reactive oxygen species (ROS) and upregulate antioxidative enzymes. Polyphenols with anticataract properties are mainly flavonoids, phenolic acids, carotenoids, and vitamins. Quercetin and catechin are the specific polyphenols that portray promising effects against ocular diseases. Both quercetin and catechin are previously detected in SBH and EBH and could also be found in fruits and vegetables. Quercetin (3,3′,4′,5,7-pentahydroxyflavone) can inhibit hydrogen peroxide-induced cataracts while catechin derivatives inhibit cataracts in rats induced by N-methyl-N-nitrosourea.
Effects on Fertility
Honey has been shown to portray positive effects on fertility by means of enhancing the hormones related to fertility. Sexual dysfunction and impaired fertility are among the adverse effects that have been associated with cigarette smoking, especially in males. A laboratory study reported that reproductive toxicity induced by cigarette smoke was alleviated by the oral consumption of EBH at 1.2 g/kg/day, which raised the successful intromission and ejaculation percentage in rats, thus resulting in increased fertility and mating rates. Besides that, noise stress is one of the stress factors, which is known to hinder male reproductivity. Noise stress has negatively impacted the cells of testicular tissue by promoting the growth of apoptotic and necrotic cells. However, with EBH and vitamin E treatment, it was observed that the cells of mature male Wistar rats which have been exposed to noise stress are enhanced and found healthy. This suggests that EBH and vitamin E have good effects on the testis parenchyma as EBH and vitamin E reduced apoptosis and necrosis in cells affected by noise stress and thereby increased cell growth and activity.
In one study, the intake of Tualang honey (EBH) produced by Apis dorsata to restraint-stressed pregnant rats at 1.2 g/kg daily resulted in favourable condition on several parameters, especially in the level of corticosterone, outcome of pregnancy, and adrenal histomorphometry. It is reported that alteration of gonadotropin levels in female rats was significantly restored with EBH administration at 1 g/kg. Regularly, diabetic rats suffer from low sperm quality; however, SBH administration to diabetic rats portrays improvement in sperm quality, with additional protective effects on spermatogenesis process even in diabetic condition. In nondiabetic rats, administration of SBH helps to increase the count of epididymal sperm count, the motility, and viability of the sperm. This could suggest for potential property of the fertility enhancer in the SBH. In conclusion, the SBH could be a great alternative in order to prevent sperm and testis damage in diabetic rats.
This current review of the Stingless Bee Honey (SBH) in comparison with EBH revealed a significant role of the SBH as a therapeutic agent in various health issues such as antidiabetic, wound healing, anticancer, treatment of eye diseases, and also in fertility. Studies have proven that the SBH has excellent potential and portrays beneficial effects as antimicrobioal, anticancer agent, improving hypertension, lipid profiles, and with some studies showing better antidiabetic effects than the EBH in vivo. In addition, other therapeutic properties are also at par or even significantly better from the much-researched EBH. In order to provide a major comprehensive understanding on the potential uses and benefits of the SBH, more systematic studies need to be carried out.
Previously, studies on SBH were done using tissue cultures, animal models, and clinical trials to demonstrate the biotherapeutic activities. However, the information on its beneficial effects is still scarce. With regard to its benefits to human health, more scientific studies and clinical trials on human subjects need to be conducted to relay a better understanding in evaluating the potential of stingless bee honey as a therapeutic agent.
There are a plethora of areas to study for researchers who are interested in the biotherapeutic effects of the SBH. In terms of quality control, methods to authenticate pure SBH need to be developed. A rapid and destructive analysis technique is required to avoid possible adulteration by irresponsible manufacturers. In return, it is expected that a quality standard can be established by the identification of its bioactive component. Since SBH is rich in antioxidants, these substances might account for some of the potential health benefits portrayed by them. Therefore, innovative efforts should be taken to fully explore and utilize these benefits. Honey-based products should be diversified, such as making supplement capsules or tablets which contain probiotics isolated from the SBH that can aid in gastrointestinal health. These properties should also be made readily in the form of topical creams or gels for wound healing or other purposes.
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