Therapeutic Potential of Malaysian Stingless Bee Propolis Extract Targeting Macrophages in Atherogenesis: A Review

Therapeutic Potential of Malaysian Stingless Bee Propolis Extract

Authors

  • Mohd Yusmaidie Aziz Department of Toxicology, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Penang, Malaysia
  • Eshaifol Azam Omar Department of Toxicology, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Penang, Malaysia
  • Nor Effa Syazuli Zulkafli Department of Biomedical Science, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Penang, Malaysia
  • Rafeezul Mohamed Department of Biomedical Science, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Penang, Malaysia

DOI:

https://doi.org/10.11594/jtls.14.01.17

Keywords:

Atherosclerosis, Foam Cells, Macrophages, Geniotrigona thoracic, Propolis

Abstract

Propolis is a sticky substance that originates from the collection of plant saps and resins by stingless bees. The bees blend this material with pollen and wax flakes, and their salivary fluids combine with the mixture to produce a potent compound that contains various chemical constituents, such as flavonoids and phenolic compounds. Numerous studies have revealed that propolis from stingless bees displays anti-inflammatory, antioxidant, immunomodulatory, and cardioprotective properties. Geniotrigona thoracica is one of the Malaysian stingless bee species, and propolis from this species is composed of a wide array of biochemical compounds and antioxidant properties that may have an anti-atherogenic effect. This review highlights the possible role of propolis from the Malaysian stingless bee G. thoracica as a macrophage-targeted therapeutic in atherogenesis, as macrophage-derived foam cell formation is integral to the development of atherosclerosis. The review first describes the characteristics, chemical content, and antioxidant properties of propolis from G. thoracica. It then discusses the pathogenesis of atherosclerosis, with a focus on macrophage-derived foam cell formation. Subsequently, the anti-atherosclerotic effects of propolis from G. thoracica are presented, and recent studies on the anti-atherosclerotic effects of propolis from honeybees worldwide are summarized for comparison. Finally, future perspectives are emphasized, highlighting the knowledge gaps that need to be investigated by researchers in this field.

References

Chuttong B, Chanbang Y, Burgett M (2014) Meliponiculture: Stingless bee beekeeping in Thai-land. Bee World 91 (2): 41-45. doi: 10.1080/0005772X.2014.11417595.

Chantawannakul P, Ramsey S (2018) The overview of honey bee diversity and health status in Asia. In Asian beekeeping in the 21st century. Springer Na-ture Singapore. 1-39. doi: 10.1007/978-981-10-8222-1_1.

Roubik DW (2006) Stingless bee nesting biology. Apidologie 37 (2): 124-143. doi: 10.1051/apido:2006026

Abd Jalil MA, Kasmuri AR, Hadi H (2017) Stingless bee honey, the natural wound healer: A review. Skin Pharmacology and Physiology 30 (2): 66-75. doi: 10.1159/000458416.

Momose K, Yumoto T, Nagamitsu T, Kato M, Naga-masu H, Sakai S, Harrison R, Itioka T, Hamid A, Inoue T (1998) Pollination biology in a lowland diptero-carp forest inSarawak, Malaysia. I. Characteristics of the plant-pollinator communityin a lowland diptero-carp forest. American Journal of Botany 85 (10): 1477-1501.

Norowi M, Mohd F, Sajap A, Rosliza J, Suri R (2010) Conservation and sustainable utilization of stingless bees for pollination services in agricultural ecosys-tems in Malaysia. In proceeding of International Seminar on Enhancement of Functional Biodiversity Relevent to Sustainable Food Production in ASPAC Tsukuba Japan 9-11 November 2010.

Kelly N, Farisya M, Kumara T, Marcela P (2014) Species diversity and external nest characteristics of stingless bees in meliponiculture. Pertanika Journal of Tropical Agricultural Science 37 (3): 293-298.

Azmi WA, Ghazi R, Nasharuddin IS (2019) Morpho-logical, nest architecture and colony characteristics of stingless bees (Hymenoptera; Apidae; Meliponini) from Tasik Kenyir, Terengganu. Social development and environmental sustainability: From ridge to reef. In Greater Kenyir Landscapes. Springer Nature Swit-zerland AG 111-21. doi: 10.1007/978-3-319-92264-5_11.

Danaraddi CS, Viraktamath S, Basavanagoud K, Bhat ARS (2009) Nesting habits and nest structure of stingless bee, Trigona iridipennis Smith at Dharwad, Karnataka. Karnataka Journal of Agricultural Scienc-es 22 (2): 310-3.

Velthuis HHW (1997) The biology of stingless bees: Universiteit Utrecht Press.

Samsudin SF, Mamat MR, Hazmi IR (2018) Taxo-nomic study on selected species of stingless bee (Hymenoptera: Apidae: Meliponini) in peninsular Malaysia. Serangga 23 (2): 203-258.

Wagh VD (2013) Propolis: a wonder bees product and its pharmacological potentials. Advances in Pharmacological Sciences 2013: 308249. doi: 10.1155/2013/308249.

Salatino A, Teixeira EW, Negri G, Message D (2005) Origin and chemical variation of Brazilian propolis. Evidence Based Complementary Alternative Medi-cine 2 (1): 33-38. doi: 10.1093/ecam/neh060.

Sforcin JM (2007) Propolis and the immune system: a review. Journal of Ethnopharmacology 113 (1): 1-14. doi: 10.1016/j.jep.2007.05.012.

Burdock GA (1998) Review of the biological proper-ties and toxicity of bee propolis (propolis). Food and Chemical Toxicology 36 (4): 347-63. doi: 10.1016/s0278-6915(97)00145-2.

Alencar SM, Oldoni TL, Castro ML, Cabral IS, Costa-Neto CM, Cury JA, Rosalen PL, Ikegaki M (2007) Chemical composition and biological activity of a new type of Brazilian propolis: red propolis. Journal of Ethnopharmacology 113 (2): 278-83. doi: 10.1016/j.jep.2007.06.005.

Maciejewicz W (2001) Isolation of flavonoid agly-cones from propolis by a column chromatography method and their identification by GC-MS and TLC methods. Journal of liquid chromatography & relat-ed technologies 24 (8):1171-1179. https://doi.org/10.1081/JLC-100103439.

Badiazaman AAM, Zin N, Annisava AR, Nafi NEM, Mohd KS (2019) Phytochemical screening and anti-oxidant properties of stingless bee Geniotrigona tho-racica propolis. Malaysian Journal of Fundamental and Applied Sciences. SI ICAFT 2018:330-335. doi: https://doi.org/10.11113/mjfas.v15n2-1.1557.

Mohd Suib MS, Omar EA, Wan Omar WA, Mohamed R (2018) Gas chromatography mass spectometry analysis of volatile compounds in ethanolic extract of propolis from Geniotrigona thoracica of Malaysian stingless bees species. International Journal of Pharmacy and Biological Sciences 9 (4): 122-127. doi: 10.22376/ijpbs.2018.9.4.p122-127.

Salim NHM, Omar EA, Omar WAW, Mohamed R (2018) Chemical constituents and antioxidant activi-ty of ethanolic extract of propolis from Malaysian stingless bee Geniotrigona thoracica species. Re-search Journal of Pharmaceutical Biological and Chemical Sciences 9 (6): 646-51.

Nazir H, Shahidan WNS, Ibrahim HA, Tuan Ismail TNN (2018) Chemical constituents of Malaysian Geniotrigona thoracica propolis. Pertanika Journal of Tropical Agricultural Science 41 (3): 955-962.

Ibrahim N, Niza N, Rodi MM, Zakaria AJ, Ismail Z, Mohd KS (2016) Chemical and biological analyses of Malaysian stingless bee propolis extracts. Malaysian Journal of Analytical Sciences 20 (2): 413-22.

Malekmohammad K, Sewell RDE, Rafieian-Kopaei M (2019) Antioxidants and Atherosclerosis: Mechanis-tic Aspects. Biomolecules 9 (8): 301. doi: 10.3390/biom9080301.

Mitra S, Deshmukh A, Sachdeva R, Lu J, Mehta JL (2011) Oxidized low-density lipoprotein and athero-sclerosis implications in antioxidant therapy. Ameri-can Journal of Medical Sciences 342 (2): 135-42. doi: 10.1097/MAJ.0b013e318224a147.

Cheng YC, Sheen JM, Hu WL, Hung YC. (2017) Poly-phenols and oxidative stress in atherosclerosis-related ischemic heart disease and stroke. Oxidative Medicine and Cell Longevity 2017: 8526438. doi: 10.1155/2017/8526438.

Awang N, Ali N, Abd Majid FA, Hamzah S, Abd Razak SB (2018) Total flavonoids and phenolic contents of sticky and hard propolis from 10 species of Indo-Malayan stingless bees. Malaysian Journal of Analyt-ical Sciences 22 (5): 877-84. doi: https://doi.org/10.17576/mjas-2018-2205-15.

Kedare SB, Singh RP (2011) Genesis and develop-ment of DPPH method of antioxidant assay. Journal of Food Science and Technology 48 (4): 412-22. doi: 10.1007/s13197-011-0251-1.

Libby P, Buring JE, Badimon L, Hansson GK, Dean-field J, Bittencourt MS, Tokgözoğlu L, Lewis EF (2019) Atherosclerosis. Nature Review. Disease Primers 5 (1): 56. doi: 10.1038/s41572-019-0106-z.

Cochain C, Zernecke A (2017) Macrophages in vas-cular inflammation and atherosclerosis. Pflugers Arch: European Journal of Physiology 469 (3-4): 485-499. doi: 10.1007/s00424-017-1941-y.

Orekhov AN (2018) LDL and foam cell formation as the basis of atherogenesis. Current Opinion in Lipid-ology 29 (4): 279-284. doi: 10.1097/MOL.0000000000000525.

Tirapelli C (2020) Oxidative stress and vascular disease. Current Hypertension Reviews. 16 (3): 162. doi: 10.2174/157340211603201127142401.

Almeida SO, Budoff M (2019) Effect of statins on atherosclerotic plaque. Trends Cardiovascular Medi-cine 29 (8): 451-455. doi: 10.1016/j.tcm.2019.01.001.

Vekic J, Zeljkovic A, Cicero AFG, Janez A, Stoian AP, Sonmez A, Rizzo M (2022) Atherosclerosis develop-ment and progression: The role of atherogenic small, dense LDL. Medicina (Kaunas) 58 (2): 299. doi: 10.3390/medicina58020299.

Bergheanu SC, Bodde MC, Jukema JW (2017) Path-ophysiology and treatment of atherosclerosis: Cur-rent view and future perspective on lipoprotein modification treatment. Netherland Heart Journal 25 (4): 231-242. doi: 10.1007/s12471-017-0959-2.

Wang D, Yang Y, Lei Y, Tzvetkov NT, Liu X, Yeung AWK, Xu S, Atanasov AG (2019) Targeting foam cell formation in atherosclerosis: Therapeutic potential of natural products. Pharmacological Reviews 71 (4): 596-670. doi: 10.1124/pr.118.017178.

Dubland JA, Francis GA (2015) Lysosomal acid li-pase: at the crossroads of normal and atherogenic cholesterol metabolism. Frontiers in Cell and Devel-opmental Biology 3: 3. doi: 10.3389/fcell.2015.00003.

Schlager S, Vujic N, Korbelius M, Duta-Mare M, Dor-ow J, Leopold C, Rainer S, Wegscheider M, Reicher H, Ceglarek U, Sattler W, Radovic B, Kratky D (2017) Lysosomal lipid hydrolysis provides substrates for li-pid mediator synthesis in murine macrophages. On-cotarget 8 (25): 40037-40051. doi: 10.18632/oncotarget.16673.

Hopkins PN (2013) Molecular biology of atheroscle-rosis. Physiological Reviews 93 (3): 1317-542. doi: 10.1152/physrev.00004.2012.

Chistiakov DA, Bobryshev YV, Orekhov AN (2016) Macrophage-mediated cholesterol handling in ath-erosclerosis. Journal of Cellular and Molecular Medi-cine 20 (1): 17-28. doi: 10.1111/jcmm.12689.

Hansson GK, Robertson AK, Söderberg-Nauclér C (2006) Inflammation and atherosclerosis. Annual Review of Pathology 1: 297-329. doi: 10.1146/annurev.pathol.1.110304.100100.

Gutierrez PS (2022) Foam cells in atherosclerosis. Arquivos Brasileiros de Cardiologia. English, Portu-guese 119 (4): 542-543. doi: 10.36660/abc.20220659.

Sukhovershin RA, Toledano Furman NE, Tasciotti E, Trachtenberg BH (2016) Local inhibition of macro-phage and smooth muscle cell proliferation to sup-press plaque progression. Methodist Debakey Cardi-ovascular Journal 12 (3): 141-145. doi: 10.14797/mdcj-12-3-141.

Dinelli G, Bonetti A, Minelli M, Marotti I, Catizone P, Mazzanti A (2006) Content of flavonols in Italian bean (Phaseolus vulgaris L.) ecotypes. Food chemis-try 99 (1): 105-14.

Rocha-Guzmán NE, Herzog A, González-Laredo RF, Ibarra-Pérez FJ, Zambrano-Galván G, Gallegos-Infante JA (2007) Antioxidant and antimutagenic activity of phenolic compounds in three different colour groups of common bean cultivars (Phaseolus vulgaris). Food chemistry 103 (2): 521-7.

Manach C, Mazur A, Scalbert A (2005) Polyphenols and prevention of cardiovascular diseases. Current Opinion in Lipidology 16(1):77-84. doi: 10.1097/00041433-200502000-00013.

Kleemann R, Verschuren L, Morrison M, Zadelaar S, van Erk MJ, Wielinga PY, Kooistra T (2011) Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis 218 (1): 44-52. doi: 10.1016/j.atherosclerosis.2011.04.023.

Sun L, Li E, Wang F, Wang T, Qin Z, Niu S, Qiu C (2015) Quercetin increases macrophage cholesterol efflux to inhibit foam cell formation through activat-ing PPARγ-ABCA1 pathway. International Journal of Clinical Experimental Pathology 8 (9): 10854-60.

Cui Y, Hou P, Li F, Liu Q, Qin S, Zhou G, Xu X, Si Y, Guo S (2017) Quercetin improves macrophage re-verse cholesterol transport in apolipoprotein E-deficient mice fed a high-fat diet. Lipids in Health and Disease 16 (1): 9. doi: 10.1186/s12944-016-0393-2.

Li XY, Kong LX, Li J, He HX, Zhou YD (2103) Kaempferol suppresses lipid accumulation in mac-rophages through the downregulation of cluster of differentiation 36 and the upregulation of scavenger receptor class B type I and ATP-binding cassette transporters A1 and G1. International Journal of Mo-lecular Medicine 31 (2): 331-8. doi: 10.3892/ijmm.2012.1204.

Iizuka M, Ayaori M, Uto-Kondo H, Yakushiji E, Tak-iguchi S, Nakaya K, Hisada T, Sasaki M, Komatsu T, Yogo M, Kishimoto Y, Kondo K, Ikewaki K (2012) Astaxanthin enhances ATP-binding cassette trans-porter A1/G1 expressions and cholesterol efflux from macrophages. Journal of Nutritional Science and Vitaminology (Tokyo) 58 (2): 96-104. doi: 10.3177/jnsv.58.96.

Mohd Suib MS, Wan Omar WA, Omar EA, Mohamed R. Ethanolic extract of propolis from the Malaysian stingless bee Geniotrigona thoracica inhibits for-mation of THP-1 derived macrophage foam cells. Journal of Apicultural Research. 60(3):478-90. https://doi.org/10.1080/00218839.2020.1720125.

Chen M, Li W, Wang N, Zhu Y, Wang X (2007) ROS and NF-kappaB but not LXR mediate IL-1beta signal-ing for the downregulation of ATP-binding cassette transporter A1. American Journal of Physiology. Cell Physiology 292 (4): C1493-501. doi: 10.1152/ajpcell.00016.2006.

Wang YF, Yang XF, Cheng B, Mei CL, Li QX, Xiao H, Zeng QT, Liao YH, Liu K (2010) Protective effect of Astragalus polysaccharides on ATP binding cassette transporter A1 in THP-1 derived foam cells exposed to tumor necrosis factor-alpha. Phytotherapy Re-search 24 (3): 393-8. doi: 10.1002/ptr.2958.

Daleprane JB, Freitas Vda S, Pacheco A, Rudnicki M, Faine LA, Dörr FA, Ikegaki M, Salazar LA, Ong TP, Abdalla DS (2012) Anti-atherogenic and anti-angiogenic activities of polyphenols from propolis. The Journal of Nutritional Biochemistery 23 (6): 557-66. doi: 10.1016/j.jnutbio.2011.02.012.

Li Y, Chen M, Xuan H, Hu F (2012) Effects of encap-sulated propolis on blood glycemic control, lipid me-tabolism, and insulin resistance in type 2 diabetes mellitus rats. Evidence Based Complementary Alter-native Medicine 2012: 981896. doi: 10.1155/2012/981896.

Azab AE, Algridi MA, Lashkham NM (2015) Hypoli-pidemic and antiatherogenic effects of aqueous ex-tract of Libyan propolis in lead acetate intoxicated male albino mice. International Journal of Science and Research 4 (3): 1060-8.

Fang Y, Li J, Ding M, Xu X, Zhang J, Jiao P, Han P, Wang J, Yao S (2014) Ethanol extract of propolis protects endothelial cells from oxidized low-density lipoprotein-induced injury by inhibiting lectin-like oxidized low density lipoprotein receptor-1-mediated oxidative stress. Experimental Biology and Medicine (Maywood) 239 (12): 1678-87. doi: 10.1177/1535370214541911.

Tian H, Sun HW, Zhang JJ, Zhang XW, Zhao L, Guo SD, Li YY, Jiao P, Wang H, Qin SC, Yao ST (2015) Ethanol extract of propolis protects macrophages from oxidized low-density lipoprotein-induced apop-tosis by inhibiting CD36 expression and endoplasmic reticulum stress-C/EBP homologous protein path-way. BMC Complementary Alternative Medicine 15: 230. doi: 10.1186/s12906-015-0759-4.

Oršolić N, Landeka Jurčević I, Đikić D, Rogić D, Odeh D, Balta V, Perak Junaković E, Terzić S, Jutrić D (2019) Effect of propolis on diet-induced hyper-lipidemia and atherogenic indices in mice. Antioxi-dants (Basel) 8 (6): 156. doi: 10.3390/antiox8060156.

Westerterp M, Fotakis P, Ouimet M, Bochem AE, Zhang H, Molusky MM, Wang W, Abramowicz S, la Bastide-van Gemert S, Wang N, Welch CL, Reilly MP, Stroes ES, Moore KJ, Tall AR (2018) Cholesterol ef-flux pathways suppress inflammasome activation, NETosis, and atherogenesis. Circulation 138 (9): 898-912. doi: 10.1161/CIRCULATIONAHA.117.032636.

Lu Y, Thavarajah T, Gu W, Cai J, Xu Q (2018) Impact of miRNA in atherosclerosis. Arteriosclerosis Throm-bosis and Vascular Biology 38 (9): e159-e170. doi: 10.1161/ATVBAHA.118.310227.

Downloads

Published

2024-02-09

Issue

Section

Review