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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2023

Open Access 01-12-2023 | Research

The anti-allergic potential of stingless bee honey from different botanical sources via modulation of mast cell degranulation

Authors: Poi Yi Aw Yong, Ashley Jia Wen Yip, Fahmida Islam, Hui Jing Hong, Yi En Teh, Chau Ling Tham, Ji Wei Tan

Published in: BMC Complementary Medicine and Therapies | Issue 1/2023

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Abstract

Background

Allergy is an inflammatory disorder affecting around 20% of the global population. The adverse effects of current conventional treatments give rise to the increased popularity of using natural food products as complementary and alternative medicine against allergic diseases. Stingless bee honey, commonly known as Kelulut honey (KH) in Malaysia, has been used locally as a traditional remedy to relieve cough and asthma. This study evaluated the anti-allergic potential of KH collected from four different botanical sources on phorbol ester 12-myristate-3-acetate and calcium ionophore-activated human mast cells.

Methods

The present study examined the inhibitory effects of all collected honey on the release of selected inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, IL-8, histamine, and β-hexosaminidase in an activated HMC. Besides that, all honey's total phenolic content (TPC) was also examined, followed by using liquid chromatography with tandem mass spectrometry (LC–MS/MS) to identify the phytochemicals in the honey. Further examination of the identified phytochemicals on their potential interaction with selected signaling molecules in an activated mast cell was conducted using computational methods.

Results

The results indicated that there were significant inhibitory effects on all selected inflammatory mediators’ release by KH sourced from bamboo (BH) and rubber tree (RH) at 0.5% and 1%, but not KH sourced from mango (AH) and noni (EH). BH and RH were found to have higher TPC values and were rich in their phytochemical profiles based on the LC–MS/MS results. Computational studies were employed to determine the possible molecular target of KH through molecular docking using HADDOCK and PRODIGY web servers.

Conclusions

In short, the results indicated that KH possesses anti-allergic effects towards an activated HMC, possibly by targeting downstream MAPKs. However, their anti-allergic effects may vary according to their botanical sources. Nevertheless, the present study has provided insight into the potential application of stingless bee honey as a complementary and alternative medicine to treat various allergic diseases.
Appendix
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Literature
1.
Oettgen H, Broide D. 1-Introduction to mechanisms of allergic disease. Allergy (Fourth Edition). 2012. p. 1–32.
2.
Cox L. Biologics and allergy immunotherapy in the treatment of allergic diseases. Immunol Allergy Clin. 2020;40:687–700.
3.
Kraneveld A, Sagar S, Garssen J, Folkerts G. The two faces of mast cells in food allergy and allergic asthma: the possible concept of Ying Yang. Biochim Biophys Acta. 2012;1822:93–9.PubMed
4.
Liu J, Xiong H, Cheng Y, Cui C, Zhang X, Zhang X. Effects of taraxasterol on ovalbumin-induced allergic asthma in mice. J Ethnopharmacol. 2013;148:787–93.PubMed
5.
Ko YJ, Kim HH, Kim EJ, Katakura Y, Lee WS, Kim GS, Ryu CH. Piceatannol inhibits mast cell-mediated allergic inflammation. Int J Mol Med. 2013;31:5195–8.
6.
Brown J, Wilson T, Metcalfe D. The mast cell and allergic diseases: role in pathogenesis and implications for therapy. Clin Exp Allergy. 2020;38:191–8.
7.
Lee M, Lee NY, Chung KS, Cheon SY, Lee KT, An HJ. Roxatidine attenuates mast cell-mediated allergic inflammation via inhibition of NF-κB and p38 MAPK activation. Sci Rep. 2017;31:41721.
8.
Laidlaw TM, Steinke JW, Tiñana AM, Feng C, Xing W, Lam BK, Paruchuri S, Boyce JA, Borish L. Characterization of a novel human mast cell line that responds to stem cell factor and expresses functional FcεRI. J Allergy Clin Immunol. 2011;127:815-22.e225.PubMedPubMedCentral
9.
Xia YX, Sun SS, Kuek LE, Lopata AL, Hulett MD, Mackay GA. Human mast cell line-1 (HMC-1) cells transfected are sensitive to IgE/antigen-mediated stimulation demonstrating selectivity towards cytokine production. Int Immunopharmacol. 2011;11:1002–11.PubMed
10.
Simons F, Simons K. Histamines and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011;128:1139–50.PubMed
11.
Puxeddu I, Levi-Schaffer F, Migliorini P. 5-Therapeutic approaches in allergic diseases. Immune Rebalancing: The Future of Immunosuppression. 2016;5:85–103.
12.
Licari A, Manti S, Marseglia A, Brambilla I, Votto M, Castagnoli R, Leonardi S, Marseglia GL. Food allergies: current and future treatments. Medicina (Kaunas). 2019;55:120.PubMed
13.
Moote W, Kim H, Ellis AK. Allergen-specific immunotherapy. Allergy Asthma. Clin Immunol. 2018;14:53.
14.
Esteraf-Oskouei T, Najafi M. Traditional and modern uses of natural honey in human diseases: a review. Iran J Basic Med Sci. 2013;16:731–42.
15.
AbdJalil MA, Kasmuri AR, Hadi H. Stingless bee honey, the natural wound healer: a review. Skin Pharmaco Physiol. 2017;30:66–75.
16.
Tuksitha L, Chen YLS, Chen YL, Wong KY, Peng CC. Antioxidant and antibacterial capacity of stingless bee honey from Borneo (Sarawak). J Asia-Pac Entomol. 2018;21:563–70.
17.
Habib HM, Al Meqbali FT, Kamal H, Souka UD, Ibrahim WH. Physicochemical and biochemical properties of honeys from arid regions. Food Chem. 2014;153:35–43.PubMed
18.
Bilica FC, da Silva B, Caon T, Mohr ETB, Vieira GN, Gonzaga LV, Vitali L, Micke G, Fett R, Dalmarco EM, Costa ACO. Investigation of phenolic compounds, antioxidant and anti-inflammatory activities in stingless bee honey (Meliponinae). Food Res Int. 2020;129:108756.
19.
Ávila S, Beux MR, Ribani RH, Zambiazi RC. Stingless bee honey: Quality parameters, bioactive compounds, health-promotion properties and modification detection strategies. Trends Food Sci Technol. 2018;81:37–50.
20.
Liu J, Ye Y, Lin T, Wang Y, Peng C. Effect of floral source on the antioxidant, antimicrobial, and anti-inflammatory activities of honeys in Taiwan. Food Chem. 2013;139:938–43.PubMed
21.
Gašić UM, Milojković-Opsenica DM, Tešić ZLJ. Polyphenols as possible markers of botanical origin of honey. J AOAC Int. 2017;100:852–61.PubMed
22.
Tan JW, Israf DA, Harith HH, Md Hashim NF, Ng CH, Shaari K, Tham CL. Anti-allergic activity of 2, 4, 6-trihydroxy-3-geranylacetophenone (tHGA) via attenuation of IgE-mediated mast cell activation and inhibition of passive systemic anaphylaxis. Toxicol Appl Pharmacol. 2017;319:47–58.PubMed
23.
Chai WY, Krishnan UG, Sabaratnam V, Tan JBL. Assessment of coffe waste in formulation of substrate for oyster mushrooms Pleurotus pulmonarius and Pleurotus floridanus. Future Foods. 2021;4:100075.
24.
Honorato RV, Koukos PI, Jimenez-Garcia B, Tsaregorodtsev A, Verlato M, Giachetti A, Rosato A, Bonvin AMJJ. Structural biology in the cloudsL the WeNMR-EOSC Ecosystem. Front Mol Biosci. 2021;8:729513.PubMedPubMedCentral
25.
van Zundert GC, Rodrigues JPGL, Trellet M, Schmitz C, Kastritis PL, Karaca E, Melquinod AS, van Dijk M, de Vries SJ, Bonvin AMJJ. The HADDOCK 2.2 webserver: User-friendly integrative modeling of biomolecular complexes. J Mol Biol. 2016;428:720–5.PubMed
26.
Kurkcouglu Z, Koukos PI, Citro N, Trellet ME, Rodrigues JPGL, Moreira IS, Roel-Touris J, Melquiond ASJ, Geng C, Shaarschidt J, et al. Performance of HADDOCK and a simple contact-based protein-ligand binding affinity predictor in the D3R Grand Challenge 2. J Comput Aided Mol Des. 2018;32:175–85.
27.
Adasme MF, Linnemann KL, Bolz SN, Kaiser F, Salentin S, Haupt VJ, Schroeder M. PLIP 2021: expanding the scope of the protein–ligand interaction profiler to DNA and RNA. Nucleic Acids Res. 2021;49:W530–4.PubMedPubMedCentral
28.
Chamchoy K, Pakotiprapha D, Pumirat P, Leartsakulpanich U, Boonyeun U. Application of WST-8 based colorimetric NAD(P)H detection for quantitative dehydrogenase assays. BMC Biochem. 2019;20:4.PubMedPubMedCentral
29.
Holowka D, Calloway N, Cohen R, Gadi D, Lee J, Smith NL, Baird B. Roles for Ca2+ mobilization and its regulation in mast cell functions. Front Immunol. 2012;3:1–10.
30.
31.
Amin FAZ, Sabri S, Mohammad SM, Ismail M, Chan KM, Ismail N, Norhaizan ME, Zawawi N. Therapeutic properties of stingless bee honey in comparison with european bee honey. Adv Pharmacol Sci. 2018;2018:6179596.
32.
Colquitt JL, Pickett K, Loveman E, Frampton GK. Surgery for weight loss in adults. Cochrane Database Syst Rev. 2014;8:698–738.
33.
Kek SP, Chin NL, Yusof YA, Tan SW, Chua LS. Total Phenolic Contents and Colour Intensity of Malaysian Honeys from the Apis spp. and Trigona spp. Bees. Agric Agric Sci Procedia. 2014;2:150–5.
34.
Ooi TC, Yaacob M, Rajab NF, Shahar S, Sharif R. The stingless bee honey protects against hydrogen peroxide-induced oxidative damage and lipopolysaccharide-induced inflammation in vitro. Saudi J Biol Sci. 2021;28:2987–94.PubMedPubMedCentral
35.
Ranneh Y, Akim AM, Hamid HA, Kazaai H, Fadel A, Mahmoud AM. Stingless bee honey protects against lipopolysaccharide induced-chronic subclinical systemic inflammation and oxidative stress by modulating Nrf2, NF-κB and p38 MAPK. Nutr Metab. 2019;16:15.
36.
37.
Asha’ari ZA, Ahmad MZ, Jihan WS, Che CM, Leman I. Ingestion of honey improves the symptoms of allergic rhinitis: evidence from a randomized placebo-controlled trial in the East coast of Peninsular Malaysia. Ann Saudi Med. 2013;33:469–75.PubMedPubMedCentral
38.
Amin K. The role of mast cells in allergic inflammation. Respir Med. 2012;106:9–14.PubMed
39.
Alangari AA, Morris K, Lwaleed BA, Lau L, Jones K, Cooper R, Jenkins R. Honey is potentially effective in the treatment of atopic dermatitis: Clinical and mechanistic studies. Immuno Inflamm Dis. 2017;5:190–9.
40.
Ranneh Y, Faisal A, Maryam Z, Abdah MA, Hasiah AH, Huzwah K. Malaysian stingless bee and Tualang honeys: A comparative characterization of total antioxidant capacity and phenolic profile using liquid chromatography-mass spectrometry. LWT – Food Sci Technol. 2018;89:1–9.
41.
Gül A, Pehlivan T. Antioxidant activities of some monofloral honey types produced across Turkey. Saudi J Biol Sci. 2018;25:1056–65.PubMedPubMedCentral
42.
Fei X, Je I, Shin T, Kim S, Seo S. Synthesis of Gallic Acid Analogs as Histamine and Pro-Inflammatory Cytokine Inhibitors for Treatment of Mast Cell-Mediated Allergic Inflammation. Molecules. 2017;22:898.PubMedPubMedCentral
43.
Fu LX, Chen T, Sun QM, Zhou PM, Guo ZP. Interleukin-35 inhibited the production of histamine and pro-inflammatory cytokines through suppression MAPKs pathway in HMC-1 cells. Allergy Asthma Clin Immunol. 2021;17:1–8.
44.
Huang Y, Yang XL, Ni YH, Xu ZM. Geraniol suppresses proinflammatory mediators in phorbol 12-myristate 13-acetate with A23187-induced HMC-1 cells. Drug Des Devel Ther. 2018;12:2897–903.PubMedPubMedCentral
45.
Min YD, Choi CH, Bark H, Son HY, Park HH, Lee S, Park JW, Park EK, Shin HI, Kim SH. Quercetin inhibits expression of inflammatory cytokines through attenuation of NF-κB and p38 MAPK in HMC-1 human mast cell line. Inflamm Res. 2007;56:210–5.PubMed
46.
Sackeyfio AC, Lugeleka OM. The anti-inflammatory effect of a crude aqueous extract of the root bark of “Ficus elastica” in the rat. Arch Int Pharmacodyn Ther. 1986;281:169–76.PubMed
47.
Yang J, Choi M, Yang SH, Cho SS, Park SJ, Shin H, Ki SH. Potent Anti-Inflammatory and Antiadipogenic Properties of Bamboo (Sasa coreana Nakai) Leaves Extract and Its Major Constituent Flavonoids. J Agric Food Chem. 2017;65(31):6665–73.PubMed
48.
Kim HN, Son KH, Jeong HJ, Park SB, Kim JD, Jeong JB. Anti-inflammatory Activity of Acacia Honey through Inhibition of NF-κB and MAPK/ATF2 Signaling Pathway in LPS-Stimulated RAW264.7 Cells. Korean J Plant Res. 2018;31:612–21.
49.
Minden-birkenmaier BA, Cherukuru K, Smith RA, Radic MZ, Bowlin GL. Manuka Honey Modulates the Inflammatory Behavior of a dHL-60 Neutrophil Model under the Cytotoxic Limit. Int J Biomater. 2019:14–20.
50.
Tonks AJ, Cooper RA, Jones KP, Blair S, Parton J, Tonks A. Honey stimulates inflammatory cytokine production from monocytes. Cytokine. 2003;21:242–7.PubMed
51.
Yücel G, Zhao Z, El-Battrawy I, Lan H, Lang S, Li X, Buljubasic F, Zimmermann WH, Cyganek L, Utikal J, et al. Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunction in human-induced pluripotent stem cell derived cardiomyocytes. Sci Res. 2017;7:2935.
52.
Sell SA, Wolfe PS, Spence AJ, Rodriguez IA, McCool JM, Petrella RL, Garg K, Ericksen JJ, Bowlin GL. A preliminary study on the potential of Manuka honey and platelet-rich plasma in wound healing. Int J Biomater. 2012;2012:313781.PubMedPubMedCentral
53.
Haiqal Ismail M, Rasyidah Badruilhisham N, Lim V, Nurdin A, Harith H, Yong Y. Comparison of antioxidant levels and anti-inflammatory activities of kelulut honey harvested at different month of intervals and its chemical compositions. Pharmacogn Mag. 2020;16:350–9.
54.
Park HH, Lee S, Son HY, Park SB, Kim MS, Choi EJ, Singh TSK, Ha JH, Lee MG, Kim JE, et al. Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells. Arch Pharm Res. 2008;31:1303–11.PubMed
55.
Carmona-Hernandez JC, Taborda-Ocampo G, González-Correa CH. Folin-Ciocalteu reaction alternatives for higher polyphenol quantitation in colombian passion fruits. Int J Food Sci. 2021;2021:8871301.PubMedPubMedCentral
56.
Miguel MG, Antunes MD, Faleiro ML. Honey as a complementary medicine. Integr Med Insights. 2017;12:1–15.
57.
Quazi A, Mohsina FP, Faheem IP, Priya S. In silico ADMET analysis, Molecular docking and in vivo anti diabetic activity of polyherbal tea bag formulation in Streptozotocin-nicotinamide induced diabetic rats. Int J Health Sci. 2022;6:343–72.
58.
Quazi A, Patwekar M, Patwekar F, Mezni A, Ahmad I, Islam F. Evaluation of Wound Healing Activity (Excision Wound Model) of Ointment Prepared from Infusion Extract of Polyherbal Tea Bag Formulation in Diabetes-Induced Rats. Evid Based Complement Alternat Med. 2022;2022:1372199.PubMedPubMedCentral
59.
Patwekar M, Patwekar F, Mezni A, Sanaullah S, Fatema SR, Almas U, Ahmad I, Tirth V, Mallick J. Assessment of antioxidative and alpha-amylase potential of polyherbal extract. Evid Based Complement Alternat Med. 2022;2022:7153526.PubMedPubMedCentral
60.
Ulusoy HG, Sanlier N. A minireview of quercetin: from its metabolism to possible mechanisms of its biological activities. Crit Rev Food Sci Nutr. 2020;60:3290–303.PubMed
61.
Liao YR, Lin JY. Quercetin Modulates Cytokines Expression and Inhibits TLR2 Expression and STAT3 Activation in Mouse Activated Inflammatory Macrophages. J Explor Res Pharmacol. 2020;5:31–41.
62.
Li X, Li K, Xie H, Xie Y, Li Y, Zhao X, Jiang X, Chen D. Antioxidant and Cytoprotective Effects of the Di-O-Caffeoylquinic Acid Family: The Mechanism, Structure-Activity Relationship, and Conformational Effect. Molecules. 2018;23:222.PubMedPubMedCentral
63.
Abdel Motaal A, Ezzat SM, Tadros MG, El-Askary HI. In vivo anti-inflammatory activity of caffeoylquinic acid derivatives from Solidago virgaurea in rats. Pharm Biol. 2016;54:2864–70.PubMed
64.
He L, Xu X, Li Y, Li C, Zhu Y, Yan H, Sun Z, Sun C, Song J, Bi Y, et al. Transciptome Analysis of Buds and Leaves Using 454 Pyrosequencing to Discover Genes Associated with the Biosynthesis of Active Ingredients in Lonicera japonica Thunb. PLoS One. 2013;8(4):e62922.PubMedPubMedCentral
65.
Cho MS, Park WS, Jung W, Qian Z, Lee D, Choi J, Lee D, Park S, Seo S, Kim H, et al. Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-κB signaling in activated HMC-1 human mast cells. Pharm Biol. 2014;52:926–32.PubMed
66.
Kang OH, An HJ, Kim SB, Mun SH, Seo YS, Joung DK, Choi JG, Shin DW, Kwon DY. Tetrandrine suppresses pro-inflammatory mediators in PMA plus A23187-induced HMC-1 cells. Int J Mol Med. 2014;33:1335–40.PubMed
67.
Ferreira De Freitas R, Schapira M. A systematic analysis of atomic protein-ligand interactions in the PDB. Med Chem Comm. 2017;8:1970–81.
68.
Xie NZ, Du QS, Li JX, Huang RB. Exploring strong interactions in proteins with quantum chemistry and examples of their applications in drug design. PLoS One. 2015;10:1–19.
Metadata
Title
The anti-allergic potential of stingless bee honey from different botanical sources via modulation of mast cell degranulation
Authors
Poi Yi Aw Yong
Ashley Jia Wen Yip
Fahmida Islam
Hui Jing Hong
Yi En Teh
Chau Ling Tham
Ji Wei Tan
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2023
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-023-04129-y

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