Stingless bee honey and its potential value : a systematic review

Email: razinah@ukm.edu.my eISSN: 2550-2166 / © 2017 The Authors. Published by Rynnye Lyan Resources Food Research 2 (2) : 124 133 (April 2018) Journal homepage: http://www.myfoodresearch.com M IN I R E V IE W Stingless bee honey and its potential value: a systematic review Yaacob, M., Rajab N.F., Shahar, S. and Sharif, R. Nutritional Sciences Programme, School of Healthcare Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia 2 Biomedical Science Programme, Faculty of Health Sciences, Universiti Kebangsaan Malaysia 3 Dietetics Programme, Faculty of Health Sciences, Universiti Kebangsaan Malaysia 4 Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia


Introduction
Honey is a natural food derived from honey bee and most commonly used as a sweetener.Besides, honey also is known for its remedial value (Rodríguez et al., 2012).
Even though there has a study on the potential of honey in treating several health problems but studies mostly are focusing on Tualang and Manuka honey compared to the stingless bee honey due to the low production of honey (Roowi et al., 2012).Therefore, there has no guarantee of their nutrients to the user since it not yet included in the Codex Alimentarius for honey (Codex, 2001).
The composition of stingless bee honey differ from other species according to some physicochemical parameters (Özbalci et al., 2013) and other studies prove that honey from stingless bees are more valuable and it has been used for a long time to treat various diseases eISSN: 2550-2166 © 2017 The Authors.Published by Rynnye Lyan Resources (Souza et al., 2006).
Stingless bees is a small bee from the species of Trigona or Meliponine and also known as Kelulut bee in Malaysia is the type of honey that has a high medicinal beneficial than other bee species which had alleged by the traditional medical practitioner (Biswa et al., 2017) They are the main pollinators among the other bees and can be found mostly in tropical and subtropical regions (Fowler, 1979) .The color of the honey is usually clearer, liquid and has a sweet and sour taste (Roowi et al., 2012).The recent studies showed that the stingless bee honey has the potential to treat colorectal cancer (Yazan et al., 2016), anti-inflammatory (Borsato et al., 2014), antimicrobial (Zainol et al., 2013;Nobre da Cruz et al., 2014;Massaro et al., 2014;Nishio et al., 2016;Medeiros et al., 2016;De Sousa et al., 2016;Nishio et al., 2016) and has an antioxidant property (Almeida Da Silva et al., 2013;Duarte et al., 2012).This review aims to prove current scientific evidence regarding the stingless bee honey and its potential value on health as anti-inflammatory, cytotoxicity, antimicrobial and also the antioxidant properties.

Search strategy
The search for articles from databases namely Scopus, Medline and Ovid, EMBASE, and PubMed were performed until October 2016.Search strategies were adjusted to well-suited with the subject headings and keywords of each database were carried out.The search terms encompass "honey" and Kelulut", "honey" and "stingless bee", "honey" and "Trigona", "honey" and "pot honey", and "honey" and "Melipon".The compatible references were re-evaluated for affirmation of the search string.In addition, pertinent reviews were also included as an additional source of literature reports.All the search databases were exported into an Endnote library to remove duplicates.

Inclusion criteria
Stingless bee is also known as Kelulut, Trigona spp, Melipona spp., Meliponine spp and pot honey bee in other literature.In this review, in vitro and in vivo studies that investigated the benefit of honey from stingless bee were included.From the databases, only stingless bee honey as anti-inflammatory, cytotoxicity, antimicrobial and antioxidant properties were included in this study.Studies published in English and Malay were taken into deliberation.

Exclusion criteria
Literature reports on propolis and behavior study of the honeybee or other species of bee were excluded from the study.The studies on physicochemical of stingless bee honey or bioactive chemical component in honey also were excluded this review.

Study selection
The prime literature search was executed by authors.All duplicate articles were first filtered out by a software and followed by hand search to verify there is no duplicate articles were included.Potential relevant papers were chosen by screening the title, abstract, and retrieval of the full article from the database search.Afterwards, the resulting irrelevant reports were rejected according to inclusion and exclusion criteria.After that, full-text articles were downloaded and then assessed for eligibility.If the papers were not published in English and Malay, these studies were excluded at this time point.

Data organization and reporting
The information acquired from each study were arranged particularly according to the data about the author's name, year of publication, type of cell or bacteria used, type of stingless bee species, experimental method, and outcomes.The inclusion studies were reported according to PRISMA guidelines (http:// www.prisma-statement.org/statement.htm).
PRISMA also provides a flowchart to illustrate the searching strategy until the assessment process.

Descriptive of selected studies
Figure 1 is an illustration of the procedure for the study selection.A total of 1796 articles were found after searching in four differences databases.1271 articles were segregated after removal of duplicates.Afterwards, 1232 articles were rejected because they did not fulfill the inclusion criteria and 39 articles were reevaluated again for the qualification.Finally, 13 articles which were not written in English or Malay language were removed and only 26 of the reports were deliberated for this review.All the 26 reports were found and further analysis regarding the type of honey from difference stingless bee species and outcomes were summarized in Tables 1-4.

Antioxidant properties of stingless bee honey
The clinical finding reported that oxidative stress can MINI REVIEW cause oxidative damage to deoxyribonucleic acid (DNA), proteins, and fats and antioxidants can stop or slow down the process of oxidative stress in the cell (Block et al., 2002).Oxidative stress can lead the development of neurological diseases (Alzheimer's disease and Parkinson's disease), atherosclerosis, joint disorders, cardiovascular diseases, lung and kidney disorders, eye disorders, cancer, aging and other degenerative diseases (Rahman et al., 2012).Therefore, antioxidant properties such as phenolic acid can decrease the oxidative stress.
Total phenolic content differs among the honey regarding their type of bee species, region, season and type of floral sources (Almeida da Silva et al., 2013).Although Apis spp. is more recognize compared to the species from a stingless bee, but the total phenolic acid of stingless bee from species Plebeia spp. was higher than Apis spp.which is 106.01 ± 9.85 mg GA equivalent/ 100g compared to Apis sp.92.34 ± 13.55 mg GA acid equivalent/ 100 g (Duarte et al., 2012).Meanwhile for antioxidant activity of Plebeia spp. is 49.91± 21.36 mg GA equivalent/ 100 g.Moreover, Almeida da Silva et al. (2013) reported that honey sample which displayed the highest total phenolic content have slightly highest ABTS + cation radical scavenging capacity.This result indicates that there is a correlation between phenolic content and antioxidant activity in the stingless bee's honey (Duarte et al., 2012;De Sousa et al., 2016).

Anti-inflammatory
Previous literature reported that phenolic compound had related to anti-inflammatory effects on the animal (Larrosa et al., 2009).Caffeic and ferulic acids, the derivatives from phenolic acid can reduce inflammation in neurovascular and able to inhibit macrophage inflammatory protein-2 (MIP-2) (Larrosa et al., 2009).Meanwhile, kaempferol showed an inhibitory effect on NO synthase (iNOS) and cyclooxygenase-2 (COX-2) (Crespo et al., 2008).The studies conducted by Borsato et al. (2014) proved that phenolic acid from an extract of honey from stingless bee had decreased the production of reactive oxygen species (ROS) in 55 ± 14%.A study done by Larrosa et al. (2009) is the early report described the anti-inflammatory activity of honey extract from stingless bee species (M.marginata) by in vivo approaches thus, conclude that the stingless bee honey able to decrease ear edema (Borsato et al., 2014).

Anti-proliferative
There had very few studies anti-proliferative of stingless bee honey on cancer cell lines.The previous studies showed the stingless bee honey showed cytotoxically sensitive to the liver hepatocellular carcinoma cell lines (HepG2) and lung bronchus carcinoma cell line (ChaGo-I).In contrast, colon carcinoma cell lines (SW620), human gastric carcinoma cell lines (KATO-III) and ductal carcinoma cell lines (BT474) were insensitive to honey (Kustiawan et al., 2014).This showed that the honey can gave a different effect on various cell lines (Porcza et al., 2016).Further studies on cytotoxicity activity of the known pure compound of kaempferol, apigenin, caffeic acid phenethyl ester (CAPE), and narigenin which are derived from phenolic acid in honey were investigated (Yazan et al., 2016).The results revealed that these compounds have cytotoxic effects on the ChaGo-I and KATO-III cell lines, KATO-III and BT474 respectively (Kustiawan et al., 2014;Yazan et al., 2016).This suggests that each compound from phenolic acid can be cytotoxic to the tested cancer cell.Meanwhile, another studied done on Sprague Dawley rats which are induced with colorectal cancer shown that the stingless bee honey able to reduce the total number of aberrant crypts (AC), crypt multiplicity and aberrant crypt foci (AFC) thus, indicated the potential of the honey as chemo-preventive agent (Yazan et al., 2016).

Antimicrobial
The antimicrobial activities of honey were reported due to phytochemicals, acidity, high osmolarity, and the presence of hydrogen peroxide in the honey (Molan, 1992).From the Table 4, honey from stingless bee has a

ABTS cation radical scavenging
The samples showed the highest antioxidant capacity has a higher total phenolic content.Crude extract was screened for in vitro cytotoxicity against the cell lines using the 3-(4, 5-dimethylthiazol-2yl) -2, 5-diphenyltetrazolium bromide assay.
Crude extract of stingless bee has cytotoxic effect to HepG2 cell line.

Discussion
This systematic review identified 26 reports on antioxidant properties of stingless bee honey and its potential value on health as anti-inflammatory, cytotoxicity, and antimicrobial (Figure 2).There are 2 studies on antioxidant properties that revealed the correlation between the total phenolic content and antioxidant properties (Duarte et al., 2012;Almeida da Silva et al., 2013).Generally, phenolic content plays a role to reduce the disease that associated with oxidative stress.By the presence of this active compound, it makes the stingless bee honey valuable for medical purpose.Meanwhile, another paper focusing on stingless bee honey from a variety of sample from differences locations which is best to know either the total phenolic compound and antioxidant are vary depending on geographic and type of floral used.The antioxidant properties also varied depend on soil type although mainly due to the type of floral sources.
The study conducted by Borsato et al. (2014) indicates that stingless bee honey extract has a topical anti-inflammatory activity by reducing the production of reactive oxygen species, leukocyte migration and as well as reduced edema.From the study, they are comparing the correlation between the presence of the phenolic compound in the stingless bee honey with the antiinflammatory effects.This is the good experimental paper which it determines anti-inflammatory by measurement ear thickness before and after treatment in which referring to the inflammation condition and also histological analysis.Moreover, this is the first report describing the anti-inflammatory activity of stingless bee honey extract by using in vivo approaches and this can lead more studies on the anti-inflammatory effect of the honey and can make it be a potential therapeutic opportunity against inflammatory (Borsato et al., 2014).
From the study done by Kuatiawan et al. (2014), stingless bee honey showed a cytotoxicity effect to most of the cell lines.Honey has a broad target of mechanism to become cytotoxic to the cell either act as antiproliferative or apoptotic (Porcza et al. 2016).Meanwhile for the ex-vivo experimental designed by the Yazan et al. (2016) by using the Sprague Dawley rats induced with colorectal cancer is the good platform to show the overall effect of the honey on the living subject.
Due to a shortage of new development of antibiotic to combat with the bacteria and multidrug resistance bacteria, usage of honey as an antimicrobial agent might be promising.Antimicrobial properties of honey may be related to the presence of flavonoids (Miorin et al., 2003).Flavonoids also can combat oxidative stress as well as inhibit the pathogens (Shashank and Abhay, 2013).

Conclusion
From the studies, stingless bee honey showed a potential for use in medicine as it contains phenolic that increases antioxidant content as well as it can decrease oxidative stress-related diseases.

Stingless bee honeys
Flow calorimetric Both Gram-positive and Gram-negative bacteria inhibited by stingless bee honey.

Staphylococcus aureus Tetragonisca angustula
The minimum inhibitory concentration The minimum inhibitory concentration is from 142.87 to 214.33 mg ml -1 .
Table 4. Antimicrobial studies of stingless bee honey (cont.)MINI REVIEW

Figure 1 .
Figure 1.Flowchart of search strategy and selection process

Table 1 .
Antioxidant analysis of stingless bee honey.

Table 2 .
Anti-inflammatory analysis of stingless bee honey.
As we know, Staphylococcus aureus is a common pathogen found in human skin and can cause infection in the presence of a wound.From the studies, bee honey can reduce the risk of infection to humans by this pathogen.Meanwhile, De Sousa et al. (2016) and Chan-Rodriguez et al. (2012) stated that this honey can control the foodborne disease by inhibiting the foodborne organism such as Escherichia coli and Staphylococcus aureus.Stingless bee honey also can be shortened the infections time for Medeiros et al. (2016) Staphylococcus aureus and Pseudomonas aeruginosa which were studied on as a model(Ilechie et al., 2012).Moreover, a study done by Kimoto-Nira and Amano (2008) proved that stingless bee honey able to protect against gastrointestinal infection in humans.Due to the emerging of the antibiotic resistant bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA), the potential of the honey to become an antibacterial agent to against this problem were proved by studies done byNishio et al.  (2016)andMedeiros et al. (2016).