Antihistamine Potential of Red Alga  Acanthophora spicifera  Through Combination  In Vivo ,  In Vitro , and  In Silico  Study

Ilmi Wahyuni; Nunuk Hariani Soekamto; Herlina Rasyid; Nurul Annisa; Risda Adriana; Alifiah Alfaniah Alfattah Putri; Djabal Nur Basir; Ahyar Ahmad; St. Fauziah; Rizal Irfandi

doi:10.22146/ijc.109199

Antihistamine Potential of Red Alga Acanthophora spicifera Through Combination In Vivo, In Vitro, and In Silico Study

https://doi.org/10.22146/ijc.109199

Ilmi Wahyuni⁽¹⁾, Nunuk Hariani Soekamto^(2*), Herlina Rasyid⁽³⁾, Nurul Annisa⁽⁴⁾, Risda Adriana⁽⁵⁾, Alifiah Alfaniah Alfattah Putri⁽⁶⁾, Djabal Nur Basir⁽⁷⁾, Ahyar Ahmad⁽⁸⁾, St. Fauziah⁽⁹⁾, Rizal Irfandi⁽¹⁰⁾

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Hasanuddin University, Jl. Perintis Kemerdekaan Km. 10, Tamalanrea, Makassar, 90245, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Hasanuddin University, Jl. Perintis Kemerdekaan Km. 10, Tamalanrea, Makassar, 90245, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Hasanuddin University, Jl. Perintis Kemerdekaan Km. 10, Tamalanrea, Makassar, 90245, Indonesia
(4) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Hasanuddin University, Jl. Perintis Kemerdekaan Km. 10, Tamalanrea, Makassar, 90245, Indonesia
(5) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Hasanuddin University, Jl. Perintis Kemerdekaan Km. 10, Tamalanrea, Makassar, 90245, Indonesia
(6) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Hasanuddin University, Jl. Perintis Kemerdekaan Km. 10, Tamalanrea, Makassar, 90245, Indonesia
(7) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Hasanuddin University, Jl. Perintis Kemerdekaan Km. 10, Tamalanrea, Makassar, 90245, Indonesia
(8) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Hasanuddin University, Jl. Perintis Kemerdekaan Km. 10, Tamalanrea, Makassar, 90245, Indonesia
(9) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Hasanuddin University, Jl. Perintis Kemerdekaan Km. 10, Tamalanrea, Makassar, 90245, Indonesia
(10) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Negeri Makassar, Jl. Daeng Tata, Makassar 90244, Indonesia
(*) Corresponding Author

Abstract

Red alga Acanthophora spicifera is a marine species with potential as a source of natural antihistamines. This study evaluated the bioactivity of its secondary metabolites through in vivo, in vitro, and in silico approaches. Extracts were obtained by successive maceration using n-hexane, ethyl acetate, and methanol. In vivo testing on BALB/c mice showed that extract administration did not cause significant weight loss. However, its effect on allergic symptoms was significant (p < 0.05), with the methanol extract identified as the most effective by the Mann–Whitney test. In vitro assays revealed a significant reduction in histamine levels (p < 0.05) during sensitization, treatment, and post-challenge phases, particularly in the methanol extract group. In silico docking demonstrated that two compounds from the methanol extract exhibited strong binding affinity to the H1 receptor (PDB ID: 3RZE), with binding energies of −6.27 and −5.06 kcal/mol. These findings suggest that A. spicifera, particularly its methanol extract, is a promising source of natural antihistamines with potential applications in the development of safer allergy treatments.

Keywords

Acanthophora spicifera; antihistamine; in vivo; in vitro; in silico

Full Text:

Full Text PDF

References

[1] Pawankar, R., Canonica, G.W., Holgate, S.T., Lockey, R.F., and Blaiss, M.S., 2013, WAO White Book on Allergy: Update 2013 Executive Summary, World Allergy Organization, Milwaukee, Wisconsin, US.

[2] Duangmee, K., Boonmuang, P., Santimaleeworagun, W., and Prasitdumrong, H., 2022, Urticaria, angioedema, and type I hypersensitivity reactions associated with fibrinolytic agents, Asian Pac. J. Allergy Immunol., 40 (4), 379–385.

[3] Xiang, Y.K., Fok, J.S., Podder, I., Yücel, M.B., Özkoca, D., Thomsen, S.F., and Kocatürk, E., 2024, An update on the use of antihistamines in managing chronic urticaria, Expert Opin. Pharmacother., 25 (5), 551–569.

[4] Jafarinia, M., Sadat Hosseini, M., Kasiri, N., Fazel, N., Fathi, F., Ganjalikhani Hakemi, M., and Eskandari, N., 2020, Quercetin with the potential effect on allergic diseases, Allergy, Asthma, Clin. Immunol., 16 (1), 36.

[5] Chen, N., Zhang, S., Javeed, A., Jian, C., Liu, Y., Sun, J., Wu, S., Fu, P., and Han, B., 2023, Structures and anti-allergic activities of natural products from marine organisms, Mar. Drugs, 21 (3), 152.

[6] Jiao, W.H., Cheng, B.H., Shi, G.H., Chen, G.D., Gu, B.B., Zhou, Y.J., Hong, L.L., Yang, F., Liu, Z.Q., Qiu, S.Q., Liu, Z.G., Yang, P.C., and Lin, H.W., 2017, Dysivillosins A-D, unusual anti-allergic meroterpenoids from the marine sponge Dysidea villosa, Sci. Rep., 7 (1), 8947.

[7] Hong, L.L., Yu, H.B., Wang, J., Jiao, W.H., Cheng, B.H., Yang, F., Zhou, Y.J., Gu, B.B., Song, S.J., and Lin, H.W., 2017, Unusual anti-allergic diterpenoids from the marine sponge Hippospongia lachne, Sci. Rep., 7 (1), 43138.

[8] Ko, S.C., Lee, D.S., Park, W.S., Yoo, J.S., Yim, M.J., Qian, Z.J., Lee, C.M., Oh, J., Jung, W.K., and Choi, I.W., 2016, Anti-allergic effects of a nonameric peptide isolated from the intestine gastrointestinal digests of abalone (Haliotis discus hannai) in activated HMC-1 human mast cells, Int. J. Mol. Med., 37 (1), 243–250.

[9] Xie, C.L., Liu, Q., Xia, J.M., Gao, Y., Yang, Q., Shao, Z.Z., Liu, G., and Yang, X.W., 2017, Anti-allergic compounds from the deep-sea-derived actinomycete Nesterenkonia flava MCCC 1K00610, Mar. Drugs, 15 (3), 71.

[10] Shu, Z., Liu, Q., Xing, C., Zhang, Y., Zhou, Y., Zhang, J., Liu, H., Cao, M., Yang, X., and Liu, G., 2020, Viridicatol isolated from deep-sea Penicillium griseofulvum alleviates anaphylaxis and repairs the intestinal barrier in mice by suppressing mast cell activation, Mar. Drugs, 18 (10), 517.

[11] Akbar, S.A., Hasan, M., Akbar, S.A., and Hasan, M., 2024, Evaluation of bioactive composition and phytochemical profile of macroalgae Gracilaria edulis and Acanthophora spicifera from the Banda Aceh coast, Indonesia, Sci. Technol. Asia, 29 (1), 194–207.

[12] Morais, S.R., Narayanan, R.R., Sushmitha, K.P., Suchithra, N., Shankar, S., and Sugumar, M., 2020, In vitro biological evaluation of Acanthophora spicifera, Res. J. Pharm. Technol., 13 (10), 4777–4783.

[13] Cutolo, E.A., Campitiello, R., Caferri, R., Pagliuca, V.F., Li, J., Agathos, S.N., and Cutolo, M., 2024, Immunomodulatory compounds from the sea: From the origins to a modern marine pharmacopoeia, Mar. Drugs, 22 (7), 304.

[14] El Shoubaky, G.A., Abdel-Daim, M.M., Mansour, M.H., and Salem, E.A., 2016, Isolation and identification of a flavone apigenin from marine red alga Acanthophora spicifera with antinociceptive and anti-inflammatory activities, J. Exp. Neurosci., 10 (1), JEN.S25096.

[15] Budiyanto, F., Albalawi, N.A., Ghandourah, M.A., Sobahi, T.R., Aly, M.M., Althagbi, H.F., Abuzahrah, S.S., Alarif, W.M., 2023, Antibacterial and biofilm prevention metabolites from Acanthophora spicifera, Open Chem., 21 (1), 20230163.

[16] Harborne, A.J., 1998, Phytochemical Methods A Guide to Modern Techniques of Plant Analysis, Springer Dordrecht, Netherlands.

[17] Mine, Y., Majumder, K., Jin, Y., and Zeng, Y., 2020, Chinese sweet tea (Rubus suavissimus) polyphenols attenuate the allergic responses in a BALB/c mouse model of egg allergy, J. Funct. Foods, 67, 103827.

[18] Gupta, H., and Gautam, G.K., 2023, Biological efficacy of Desmostachya bipinnata grass against allergy and hypersensitivity using different experimental models, Res. J. Pharm. Technol., 16 (10), 4543–4548.

[19] Mine, Y., Jin, Y., Zhang, H., Rupa, P., Majumder, K., Sakurai, T., Taniguchi, Y., Takagaki, R., Watanabe, H., and Mitsuzumi, H., 2019, Therapeutic effects of isomaltodextrin in a BALB/c mouse model of egg allergy, J. Funct. Foods, 55 (6), 305–311.

[20] Xu, L., Zhou, J., Eremin, S., Dias, A.C.P., and Zhang, X., 2020, Development of ELISA and chemiluminescence enzyme immunoassay for quantification of histamine in drug products and food samples, Anal. Bioanal. Chem., 412 (19), 4739–4747.

[21] Daina, A., Michielin, O., and Zoete, V., 2017, SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep., 7 (1), 42717.

[22] Akram, A., Su, C.H., and Fu, C.C., 2024, Targeting small druggable compounds against 3RZE histamine H1 receptor as potential of anti-allergic drug applying molecular modeling approach, Future J. Pharm. Sci., 10 (1), 76.

[23] Meng, E.C., Goddard, T.D., Pettersen, E.F., Couch, G.S., Pearson, Z.J., Morris, J.H., and Ferrin, T.E., 2023, UCSF ChimeraX: Tools for structure building and analysis, Protein Sci., 32 (1), e4792.

[24] Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., and Olson, A.J., 2009, Software news and updates AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, J. Comput. Chem., 30 (16), 2785–2791.

[25] Shamsian, S., Sokouti, B., and Dastmalchi, S., 2024, Benchmarking different docking protocols for predicting the binding poses of ligands complexed with cyclooxygenase enzymes and screening chemical libraries, Bioimpacts., 14 (2), 29955.

[26] Aziz, M., Ejaz, S.A., Zargar, S., Akhtar, N., Aborode, A.T., Wani, T.A., Batiha, G.E., Siddique, F., Alqarni, M., and Akintola, A.A., 2022, Deep learning and structure-based virtual screening for drug discovery against NEK7: A novel target for the treatment of cancer, Molecules, 27 (13), 4098.

[27] Zubia, M., Fabre, M.S., Kerjean, V., Le Lann, K.L., Stiger-Pouvreau, V., Fauchon, M., and Deslandes, E., 2009, Antioxidant and antitumoural activities of some Phaeophyta from Brittany coasts, Food Chem., 116 (3), 693–701.

[28] Bello, I., Bakkouri, A.S., Tabana, Y.M., Al-Hindi, B., Al-Mansoub, M.A., Mahmud, R., and Asmawi, M.Z., 2016, Acute and sub-acute toxicity evaluation of the methanolic extract of Alstonia scholaris stem bark, Med. Sci., 4 (1), 4.

[29] Linton, S., Hossenbaccus, L., and Ellis, A.K., 2023, Evidence-based use of antihistamines for treatment of allergic conditions, Ann. Allergy, Asthma, Immunol., 131 (4), 412–420.

[30] Al-Khayri, J.M., Sahana, G.R., Nagella, P., Joseph, B.V., Alessa, F.M., and Al-Mssallem, M.Q., 2022, Flavonoids as potential anti-inflammatory molecules: A review, Molecules, 27 (9), 2901.

[31] Jayashika, B.J., 2025, Solvent-dependent phytochemical diversity in Justicia tranquebariensis: A comparative analysis of methanol and ethyl acetate extractions, Int. J. Multidiscip. Res., 7 (3), 1–7.

[32] Chen, X., Li, H., Zhang, B., and Deng, Z., 2022, The synergistic and antagonistic antioxidant interactions of dietary phytochemical combinations, Crit. Rev. Food Sci. Nutr., 62 (20), 5658–5677.

[33] Kim, Y., Lee, S., Jin, M., Choi, Y.A., Choi, J.K., Kwon, T.K., Khang, D., and Kim, S.H., 2025, Aspalathin, a primary rooibos flavonoid, alleviates mast cell-mediated allergic inflammation by the inhibition of FcεRI signaling pathway, Inflammation, 48 (1), 199–211.

[34] Ahmad, B., Khan, I., Bashir, S., and Azam, S., 2012, Chemical composition and antifungal, phytotoxic, brine shrimp cytotoxicity, insecticidal and antibacterial activities of the essential oils of Acacia modesta, J. Med. Plants Res., 6 (31), 4653–4659.

[35] Lin, X.M., Chen, A.J., Zhang, H.M., Kuang, Z.Z., Chen, R., Wu, M.D., Chen, J., Ma, X., Zhao, L., Xing, Y., and Ni, H., 2025, Anti-inflammatory activity and mechanism of stearic acid extract from purslane, Food Sci. Nutr., 13(7), e70596.

[36] Huang, X.L., Wang, D.W., Liu, Y.Q., and Cheng, Y.X., 2022, Diterpenoids from Blumea balsamifera and their anti-inflammatory activities, Molecules, 27 (9), 2890.

[37] Rosa, G.P., Seca, A.M.L., Pinto, D.C.G.A., and Barreto, M.C., 2024, New phytol derivatives with increased cosmeceutical potential, Molecules, 29 (20), 4917.

[38] Lipinski, C.A., Lombardo, F., Dominy, B.W., and Feeney, P.J., 1997, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv. Drug Delivery Rev., 23 (1-3), 3–25.

[39] Soekamto, N.H., Bahrun, B., Okino, T., Rasyid, H., Pudjiastuti, P., Hadisaputri, Y.E., and Zainul, R., 2024, Chemotherapeutic prospects of organic extracts of Bornetella nitida from Selayar Island, Kuwait J. Sci., 51 (3), 100223.

[40] Riza, Y.M., Parves, M.R., Tithi, F.A., and Alam, S., 2019, Quantum chemical calculation and binding modes of H1R: A combined study of molecular docking and DFT for suggesting therapeutically potent H1R antagonist, In Silico Pharmacol., 7 (1), 1.

[41] Lopes, A.J.O., Vasconcelos, C.C., Pereira, F.A., Silva, R.H., Queiroz, P.F., Fernandes, C.V., Garcia, J.B., Ramos, R.M., Rocha, C.Q., Lima, S.T., Cartágenes, M.D., and Ribeiro, M.N., 2019, Anti-inflammatory and antinociceptive activity of pollen extract collected by stingless bee Melipona fasciculata, Int. J. Mol. Sci., 20 (18), 4512.

DOI: https://doi.org/10.22146/ijc.109199