Potensi ekstrak maggot lalat tentara hitam Hermetia illucens (Linnaeus) dalam regulasi mekanisme antioksidan selular dan antiradang: Kajian in silico

The potential of black soldier fly Hermetia illucens (Linnaeus) maggot extracts in the regulation of cellular antioxidant and anti-inflammatory mechanisms: In silico study

Authors

  • Sulistiyani Departemen Biokimia, Fakutas Matematika dan Ilmu Pengetahuan Alam, IPB University, Indonesia
  • Muhamad Fajar Firdaus Departemen Biokimia, Fakutas Matematika dan Ilmu Pengetahuan Alam, IPB University, Indonesia
  • Ria Heni Sigiro Departemen Biokimia, Fakutas Matematika dan Ilmu Pengetahuan Alam, IPB University, Indonesia
  • Abdjad Asih Nawangsih Departemen Proteksi Tanaman, Fakultas Pertanian, IPB University, Indonesia
  • Ukhradiya Magharaniq Safira Purwanto Departemen Biokimia, Fakutas Matematika dan Ilmu Pengetahuan Alam, IPB University, Indonesia
  • Dimas Andrianto Departemen Biokimia, Fakutas Matematika dan Ilmu Pengetahuan Alam, IPB University, Indonesia

DOI:

https://doi.org/10.5994/jei.20.3.223

Keywords:

molecular docking, NF-kappa B kinase inhibitor, NRF2 activator, vegetable waste

Abstract

The potential of black soldier fly (Hermetia illucens (Linnaeus), BSF) maggots as the source of biopharmaca, has not been extensively studied. This research aimed to identify bioactive compunds in BSF maggot extract that potentially activate antioxidant signaling mechanism. BSF maggots fed with vegetable waste were extracted based on maceration method with water, methanol, and acetone as solvents. Forty bioactive compounds were identified by liquid chromatography-mass spectrometry: 15 were in the aqueous extract, 13 were from methanolic extract, and 12 were in the acetone extract. Most of those compounds (90%) were having high bioavailability score (= 0.55 or more) and relatively low toxicity (500 mg/Kg<LD50<5000mg/Kg BW). Molecular docking predicted that there were 26 bioactive compounds potential to activate cellular antioxidant signaling through activation of NRF2 transcription factor, better than the commercial NRF2 activator. The aqueous extract compound with PubChem CID: 73775828 was the best one that inhibited NRF2 signaling by binding to Keap-1 protein (PDB ID: 6FFM) with Gibbs free energy (ΔG) = -6.08 Kcal/mol and dissociation constant (Kd) = 3.58 í— 10-5 µM. Whereas inhibition of inflammation via NF-kappa B signaling was shown by an aqueous extract compound verpacamide A which bound inhibitor NF-kappa B kinase (IKK2) (PDB ID: 4KIK) with ΔG = -5.024 kcal/mol; Kd = 0.207 í— 103 µM. This potency was better than that of aspirin. In conclusion, BSF maggot extracts are source of biopharmaca with potential cellular antioxidant and anti-inflammatory activity.

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References

Abed DA, Goldstein M, Albanyan H, Jin H, Hu L. 2015. Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents. Acta Pharmaceutica Sinica B. 5:285–299. DOI: https://doi.org/10.1016/j.apsb.2015.05.008.

Ali F, Khan BA, Sarwat, Sulatana. 2016. Wedelolactone mitigates UVB induced oxidative stress, inflammation and early tumor promotion events in murine skin: plausible role of NFkB pathway. European Journal of Pharmacology. 789:253–264. DOI: https://doi.org/10.1016/j.ejphar.2016.05.008.

Ali NSM, Salleh AB, Leow TC, Rahman RNZRA, Ali MSM. 2020. The influence of calcium toward order/disorder conformation of repeat-in-toxin (RTX) structure of family I.3 lipase from Pseudomonas fluorescens AMS8. Toxins (Basel). 12:1–14. DOI: https://doi.org/10.3390/toxins12090579.

Andari G, Ginting NM, Nurdiana R. 2021. Larva black soldier fly (Hermetia illucens) sebagai agen pereduksi sampah dan alternatif pakan ternak. Jurnal Ilmiah Peternakan Terpadu. 9:246–252. DOI: https://dx.doi.org/10.23960/jipt.

Banerjee P, Eckert AO, Schrey AK, Preissner R. 2018. ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Research 46:W257–W263. DOI: https://doi.org/10.1093/nar/gky318.

Cheseto X, Kuate SP, Tchouassi DP, Ndung’u M, Teal PEA, Torto B. 2015. Potential of the desert locust Schistocerca gregaria (Orthoptera: Acrididae) as an unconventional source of dietary and therapeutic sterols. PLoS ONE 10: e0127171. DOI: https://doi.org/10.1371/journal.pone.0127171.

Čičková H, Newton GL, Lacy RC, Kozánek M. 2015. The use of fly larvae for organic waste treatment. Waste Management. 35:68–80. DOI: https://doi.org/10.1016/j.wasman.2014.09.026.

Choy KW, Murugan D, Leong XF, Abas R, Alias A, Mustafa MR. 2019. Flavonoids as natural anti-inflammatory agents targeting nuclear factor-kappa B (NFkB) signaling in cardiovascular diseases: A mini review. Frontiers in Pharmacology. 10:1–8. DOI: https://doi.org/10.3389/fphar.2019.01295.

Daina A, Michielin O, Zoete V. 2017. SwissADME: A free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules. Scientific Reports. 7:1–13. DOI: https://doi.org/10.1038/srep42717.

Durai P, Shin HJ, Achek A, Kwon HK, Govindaraj RG, Panneerselvam S, Yesudhas D, Choi J, No KT, Choi S. 2017. Toll-like receptor 2 antagonists identified through virtual screening and experimental validation. FEBS Journal. 284:2264–2283. DOI: https://doi.org/10.1111/febs.14124.

Frelin C, Imbert V, Griessinger E, Loubat A, Dreanno M, Peyron JF. 2003. AS602868, a pharmacological inhibitor of IKK2, reveals the apoptotic potential of TNF-α in jurkat leukemic cells. Oncogene. 22:8187–8194. DOI: https://doi.org/10.1038/sj.onc.1206963.

Guan L, Yang H, Cai Y, Sun L, Di P, Li W, Liu G, Tang Y. 2019. Admet-score- a comprehensive scoring function for evaluation of chemical drug-likeness. MedChemComm. 10:148–157. DOI: https://doi.org/10.1039/C8MD00472B.

Hasaballah AI, Shehata AZI, Shehab AM. 2019. Antioxidant and anticancer activities of some maggots methanol extracts. Egyptian Academic Journal of Biological Sciences. 12:111–119. DOI: https://doi.org/10.21608/eajbsa.2019.26722.

He F, Ru X, Wen T. 2020. NRF2, a transcription factor for stress response and beyond. International Journal of Molecular Sciences. 21:4777. DOI: https://doi.org/10.3390/ijms21134777.

Hsiao S-W, Kuo I-C, Su C-W, Wang Y-H, Mei H-C, Lee C-K. 2022. Metabolite characterisation and profiling of Hermetia illucens L. larvae at various growth stages using Sesamum indicum residues as nutrient source. Journal of Insects as Food and Feed. 8:223–235. DOI: https://doi.org/10.3920/JIFF2021.0045.

Ibrahim SRM, Fadil SA, Fadil HA, Eshmawi BA, Mohamed SGA, Mohamed GA. 2022. Fungal naphtalenones; promising metabolites for drug discovery: Structures, biosynthesis, sources, and pharmacological potential. Toxins. 14:154. DOI: https://doi.org/10.3390/toxins.

Jain AN, Nicholls A. 2008. Recommendation for evaluation of computation methods. Journal of Computer-Aided Molecular Design. 22:133–139. DOI: https://doi.org/10.1007/s10822-008-9196-5.

Kim YB, Kim DH, Jeong SB, Lee JW, Kim TH, Lee HG, Lee KW. 2020. Black soldier fly larvae oil as an alternative fat source in broiler nutrition. Poultry Science. 99:3133–3143. DOI: https://doi.org/10.1016/j.psj.2020.01.018.

Kinasih I, Putra RE, Permana AD, Gusmara FF, Nurhadi MY, Anitasari RA. 2018. Growth performance of black soldier fly larvae (Hermetia Illucens) fed on some plant based organic wastes. HAYATI Journal of Biosciences. 25:79–84. DOI: https://doi.org/10.4308/hjb.25.2.79.

Kobayashi E, Suzuki T, Yamamoto M. 2013. Roles nrf2 playsin myeloid cells and related disorders. Oxidative Medicine and Cellular Longevity. 2013:7. DOI: https://doi.org/10.1155/2013/529219.

Krieger E, Vriend G. 2015. New ways to boost molecular dynamics simulations. Journal of Computational Chemistry. 36:996–1007. DOI: https://doi.org/10.1002/jcc.23899.

Lee J, Kim YM, Park YK, Yang YC, Jung BG, Lee BJ. 2018. Black soldier fly (Hermetia illucens) larvae enhances immune activities and increases survivability of broiler chicks against experimental infection of Salmonella gallinarum. Journal of Veterinary Medical Science. 80:736–740. DOI: https://doi.org/10.1292/jvms.17-0236.

Lee S, Hu L. 2020. Nrf2 activation through the inhibition of Keap1-Nrf2 protein-protein interaction. Medical Chemistry Research. 29:846-867. DOI: https://doi.org/10.1007/s00044-020-02539-y.

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. 2012. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews. 64:4–17. DOI: https://doi.org/10.1016/j.addr.2012.09.019.

Li Q, Zheng L, Qiu N, Cai H, Tomberlin JK, Yu Z. 2011. Bioconversion of dairy manure by black soldier fly (Diptera: Stratiomyidae) for biodiesel and sugar production. Waste Management. 31:1316–1320. DOI: https://doi.org/10.1016/j.wasman.2011.01.005.

Liu S, Misquitta YR, Olland A, Johnson MA, Kelleher KS, Kriz R, Lin LL, Stahl M, Mosyak. 2013. Crystal structure of human IκB Kinase B asymmetric dimer. The Journal of Biological Chemistry. 288:22758–22767. DOI: https://doi.org/10.1074/jbc.M113.482596.

Lu J, Guo Y, Muhmood A, Lv Z, Zeng B , Qiu Y, Zhang L, Wang P, Ren L. 2022. Food waste management employing uv-induced black soldier flies: Metabolomic analysis of bioactive components, antioxidant properties, and antibacterial potential. International Journal of Environmental Research and. Public Health. 19:6614. DOI: https://doi.org/10.3390/ijerph19116614.

Marrouchi R, Benoit E, Le Caer J-P, Belayouni N, Belghith H , Molgó J, Kharrat R. 2013. Toxic C17-sphinganine analogue mycotoxin, contaminating Tunisian mussels, causes flaccid paralysis in rodents. Marine Drugs. 11:4724–4740. DOI: https://doi.org/10.3390/md11124724.

Mlcek JM, Borkovcova M, Bednarova M. 2014. Biologically active substances of edible insects and their use in agriculture, veterinary and human medicine-a review. Journal of Central European Agriculture. 15:225–237. DOI: https://doi.org/10.5513/JCEA01/15.4.1533.

Miao Y, Hu Y, Yang J, Liu T, Wang X. 2019. Natural source, bioactivity and synthesis of benzofuran derivatives. RSC Advances. 9:27510–27540. DOI: https://doi.org/10.1039/C9RA04917G.

Muchammad Z. 2019. Uji Khasiat Ekstrak Maggot Black Soldier Fly (Hermetia illucens) sebagai Antibakteri pada Penyakit Tifus. Skripsi. Bogor: Institut Pertanian Bogor.

Musundire R, Zvidzai CJ, Chidewe C, Samende BK, Manditsera FA. 2014. Nutrient and anti-nutrient composition of Henicus whellani (Orthoptera: Stenopelmatidae), an edible ground cricket, in south-eastern Zimbabwe. International Journal of Tropical Insect Science. 34:223–231. DOI: https://doi.org/10.1017/S1742758414000484.

Muller A, Wolf D, Gutzeit HO. 2017. The black soldier fly, Hermetia illucens—A promising source for sustainable production of proteins, lipids and bioactive substances. Zeitschrift fur Naturforschung. C, Journal of Biosciences. 72:351–363. DOI: https://doi.org/10.1515/znc-2017-0030.

Patel S, Sangeeta S. 2018. Pesticides as the drivers of neuropsychotic diseases, cancers, and teratogenicity among agro-workers as well as general public. Environmental Science and Pollution Research. 26:91–100. DOI: https://doi.org/10.1007/s11356-018-3642-2.

Patiassana MT, Izzy SN, Haryandi, Nealma S. 2020. Studi laju umpan pada proses biokonversi dengan variasi jenis sampah yang dikelola PT. Biomagg Sinergi Internasional menggunakan larva black soldier fly (Hermetia illucens). Jurnal Tambora. 4:86–95.

Patwardhan RS, Sharma D, Thoh M, Checker R, Sandur SK. 2016. Baicalein exhibits anti-inflammatory effects via inhibition of NF-κB trans-activation. Biochemical Pharmacology. 108:75–89. DOI: https://doi.org/10.1016/j.bcp.2016.03.013.

Pires DEV, Blundell TL, Ascher DB. 2015. pkCSM: Predicting small-molecule pharmacokinetic properties using graph-based signatures. Journal of Medical Chemistry. 58:4066−4072. DOI: https://doi.org/10.1021/acs.jmedchem.5b00104.

Rabani V, Cheatsazan H, DavaniS. 2019. Proteomics and lipidomics of black soldier fly (Diptera: Stratiomyidae) and blow fly (Diptera: Calliphoridae) larvae. Journal of Insect Science. 19:1–9. DOI: https://doi.org/10.1093/jisesa/iez050.

Serasanambati M, Chilakapati SR. 2016. Function of nuclear factor kappa B (NF-kB) in human diseases-A Review. South Indian Journal of Biological Sciences. 2:368–38. DOI: https://doi.org/10.22205/sijbs/2016/v2/i4/103443.

Shumo M, Khamis FM, Tanga CM, Fiaboe KKM, Subramanian S, Ekesi S , van Huis A, Borgemeister C. 2019a. Influence of temperature on selected life-history traits of black soldier fly (Hermetia illucens) reared on two common urban organic waste streams in Kenya. Animals. 9:79. DOI: https://doi.org/10.3390/ani9030079.

Shumo M, Osuga IM, Khamis FM, Tanga CM, Fiaboe KKM, Subramanian S, Ekesi S, Van Huis A, Borgemeister C. 2019b. The nutritive value of black soldier fly larvae reared on common organic waste streams in Kenya. Scientific Reports. 9:1–13. DOI: https://doi.org/10.1038/s41598-019-46603-z.

Siddiqui SA, Ristow B, Rahayu T, Putra NS, Yuwono NW, Nisa K, Mategeko B, Smetana S, Saki M, Nawaz A, Nagdalian A. 2022. Black soldier fly larvae (BSFL) and their affinity for organic waste processing. Waste Management. 140:1–13. DOI: https://doi.org/10.1016/j.wasman.2021.12.044.

Silva TA, Braga MC, Santana GOS, Araujo FS, Pogue R, Dias SC, Franco OL, Carvalho JL. 2018. Breaking the frontiers of cosmetology with antimicrobial peptides. Biotechnology Advances. 36:2019–2031. DOI: https://doi.org/10.1016/j.biotechadv.2018.08.005.

Solt LA, May MJ. 2008. The IκB kinase complex: Master regulator of NF-κB signaling. Immunologic Researceh. 42:3–18. DOI: https://doi.org/10.1007/s12026-008-8025-1.

Tong KI, Kobayashi A, Katsuoka F, Yamamoto M. 2006. Two-site substrate recognition model for the Keap1-Nrf2 system: A hinge and latch mechanism. Biological Chemistry. 387:1311–1320. DOI: https://doi.org/10.1515/bc.2006.164.

Vergne C, Boury-Esnault N, Perez T, Martin M-T, Adeline M-T, Dau ETH, Al-Mourabit A. 2006. Verpacamides A−D, a sequence of C 11 N 5 diketopiperazines relating cyclo(Pro-Pro) to Cyclo(Pro-Arg), from the marine sponge Axinella vaceleti: Possible biogenetic precursors of Pyrrole-2-aminoimidazole alkaloids. Organic Letters. 8:2421–2424. DOI: https://doi.org/10.1021/ol0608092.

Vogel H, Müller A, Heckel DG, Gutzeit H, Vilcinskas A. 2018. Nutritional immunology: Diversification and diet-dependent expression of antimicrobial peptides in the black soldier fly Hermetia illucens. Developmental and Comparative Immunology. 78:141–148. DOI: https://doi.org/10.1016/j.dci.2017.09.008.

Wang R, Luo Y, Lu Y, Wang D, Wang T, Pu W, Wang Y. 2019. Maggot extracts alleviate inflammation and oxidative stress in acute experimental colitis via the activation of Nrf2. Oxidative Medicine and Cellular Longevity. 2019:4703253. DOI: https://doi.org/10.1155/2019/4703253.

Wang R, Wang D, Wang H, Wang T, Weng Y, Zhang Y, Luo Y, Lu Y, Wang Y. 2021. Therapeutic targeting of Nrf2 signaling by maggot extracts ameliorates inflammation associated intestinal fibrosis in chronic DSS-induced colitis. Front Immunology. 12:1–16. DOI: https://doi.org/10.3389/fimmu.2021.670159.

Wardana AH. 2016. Black soldier fly (Hermetia illucens) sebagai sumber protein alternatif untuk pakan ternak. WARTAZOA. 26:69–78. DOI: https://doi.org/10.14334/wartazoa.v26i2.1327.

Yantina N. 2016. Evaluasi Bahan Pakan Sumber Protein Alternatif terhadap Kandungan Nutrien dan Kecernaan secara In Vitro. Skripsi. Bogor: Institut Pertanian Bogor.

Yu C, Xiao JH. 2021. The Keap1-Nrf2 system: A mediator between oxidative and aging. Oxidative Medicine and Cellular Longevity. 1–19. DOI: https://doi.org/10.1155/2021/6635460.

Zeitz JO, Fennhoff J, Kluge H, Stangl GI, Eder K. 2015. Effects of dietary fats rich in lauric and myristic acid on performance, intestinal morphology, gut microbes, and meat quality in broilers. Poultry Science. 94:2404–2413. DOI: https://doi.org/10.3382/ps/pev191.

Published

2024-01-03

How to Cite

Sulistiyani, Firdaus, M. F., Sigiro, R. H., Nawangsih, A. A., Purwanto, U. M. S., & Andrianto, D. (2024). Potensi ekstrak maggot lalat tentara hitam Hermetia illucens (Linnaeus) dalam regulasi mekanisme antioksidan selular dan antiradang: Kajian in silico: The potential of black soldier fly Hermetia illucens (Linnaeus) maggot extracts in the regulation of cellular antioxidant and anti-inflammatory mechanisms: In silico study. Jurnal Entomologi Indonesia, 20(3), 223. https://doi.org/10.5994/jei.20.3.223

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