Sains Malaysiana 51(5)(2022): 1475-1485

http://doi.org/10.17576/jsm-2022-5105-17

Anti-Inflammatory and Antioxidant Activity of Syzygium polyanthum (Wight) Walp

(Aktiviti Anti-Radang dan Antioksidan Syzygium polyanthum (Wight) Walp.)

CARLA WULANDARI SABANDAR^1,5, JURIYATI JALIL^1,*, NORIZAN AHMAT^2,3, NOR-ASHILA ALADDIN¹, NIK KHAIRUNISSA NIK ABDULLAH ZAWAWI^2,3 & IDIN SAHIDIN⁴

¹Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia,

Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Federal Territory, Malaysia

²Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor Darul Ehsan, Malaysia

³Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia

⁴Faculty of Pharmacy, Universitas Halu Oleo, 93232 Kendari, Southeast Sulawesi, Indonesia

⁵Department of Pharmacy, Faculty of Science and Technology, Universitas Sembilanbelas November Kolaka, Jalan Pemuda, 93517 Kolaka, Southeast Sulawesi, Indonesia

Received: 29 January 2021/Accepted: 8 October 2021

Abstract

Syzygium polyanthum has been used as folk medicine to treat ailments related to oxidative stress and inflammation. In this study, the  anti-inflammatory and antioxidant activity of stem bark and root bark of the plant were investigated. The experiments that have been carried out were estimation of total phenolic and total flavonoid in the methanol extracts and fractions of both parts, isolation and structure elucidation of chemical compounds, anti-inflammatory activity evaluation based on inhibition of prostaglandin E₂ production in the LPS-induced human whole blood using radioimmunoassay technique as well as antioxidant activity based on assays by using free radical scavenging DPPH and FRAP. Results showed high amounts of phenolics and flavonoids in both parts of S. polyanthum. Seven compounds were succesfully isolated from the stem bark and identified as stigmasterol (1), 8-hydroxy-6-methoxy-3-pentylisocoumarin (2), 3,3’-di-O-methylellagic acid (3), methylgallate (4), asiatic acid (5), arjunolic acid (6), and daucosterol (7). The ethyl acetate fraction of the root bark showed potent inhibitory activity on the production of PGE₂ (IC₅₀ 3.03 ± 0.83 μg/mL). The methanol extract of the stem bark displaying promising DPPH scavenging activity (SC₅₀= 2.82 ± 0.1 μg/mL) and FRAP activity (7.02 ± 0.1 μg/μg of equivalent trolox amount). Compounds 1, 5, 6 and 7 showed pronounced inhibitory activity on the PGE₂ production with IC₅₀ranging from 0.052 to 1.25 μM. Meanwhile, compound 4 exhibited antioxidant activity toward DPPH (SC₅₀10.60 μM) and FRAP (20.5 ± 1.0 μg/μg). The study concluded that S. polyanthum as a potential source for therapeutic agents with anti-inflammatory and antioxidant activities.

Keywords: Arjunolic acid; asiatic acid; myrtaceae; prostaglandin E₂; Syzygium polyanthum

Abstrak

Syzygium polyanthum telah digunakan dalam perubatan tradisi untuk merawat penyakit yang berkaitan dengan tekanan oksidatif dan radang. Penyelidikan ini dijalankan untuk mengkaji aktiviti anti-radang dan antioksidan kulit batang dan kulit akar S. polyanthum. Uji kaji yang dijalankan adalah untuk menentukan jumlah sebatian fenol dan flavonoid di dalam ekstrak dan fraksi metanol kedua-dua bahagian tumbuhan, pemisahan dan pengenalpastian struktur sebatian kimia, penilaian aktiviti anti-radang melalui perencatan penghasilan prostaglandin E₂ di dalam darah manusia diaruh-lipopolisakarida (LPS) dengan menggunakan teknik radioimunoasai serta aktiviti antioksidan menggunakan asai DPPH dan FRAP. Hasil kajian menunjukkan kandungan sebatian fenol dan flavonoid yang tinggi di dalam kedua-dua bahagian tumbuhan S. polyanthum. Tujuh sebatian telah berjaya dipencilkan daripada kulit batang S. polyanthum iaitu stigmasterol (1), 8-hidroksi-6-metoksi-3-pentilisokoumarin (2), 3,3’-di-O-asid metilelagik (3), metilgalat (4), asid asiatik (5), asid arjunolik (6) dan daukosterol (7). Fraksi etil asetat kulit akar S. polyanthum menunjukkan aktiviti perencatan yang poten terhadap penghasilan PGE₂ (IC₅₀ 3.03 ± 0.83 μg/mL). Ekstrak metanol kulit batang menunjukkan aktiviti hapus-sisa DPPH (SC₅₀= 2.82 ± 0.1 μg/mL) dan aktiviti FRAP (7.02 ± 0.1 μg/μg bersamaan dengan jumlah trolox). Sebatian 1, 5, 6 dan 7 menunjukkan aktiviti perencatan terhadap penghasilan PGE₂ dengan nilai IC₅₀antara 0.052 ke 1.25 μM. Selain itu, sebatian 4 menunjukkan aktiviti antioksidan terhadap DPPH (SC₅₀10.60 μM) dan aktiviti FRAP (20.5 ± 1.0 μg/μg). Kajian ini menyimpulkan bahawa tumbuhan S. polyanthum berpotensi sebagai sumber bagi agen terapeutik untuk aktiviti anti-radang dan antioksidan.

Kata kunci: Asid arjunolik; asid asiatik; myrtaceae; prostaglandin E₂; Syzygium polyanthum

References

Alok, S., Jain, S.K., Verma, A., Kumar, M., Mahok, A. & Sabharwal, M. 2014. Herbal antioxidant in clinical practice: A review. Asian Pacific Journal of Tropical Biomedicine 4(1): 78-84.

Arulselvan, P., Fard, M.T., Tan, W.S., Gothai, S., Fakurazi, S., Norhaizan, M.E. & Kumar, S.S. 2016. Role of antioxidants and natural products in inflammation. Oxidative Medicine and Cellular Longevity 2016(1): 5276130.

Attiq, A., Jalil, J., Husain, K. & Ahmad, W. 2018. Raging the war against inflammation with natural products. Frontiers in Pharmacology 9: 976.

Ayoola, G.A., Coker, H.A.B., Adesegun, S.A., Adepoju-Bello, A.A., Obawey, K., Ezennia, E.C. & Atangbayila, T.O. 2008. Phytochemical screening and antioxidant activities of some selected medicinal plants used for malaria therapy in southwestern Nigeria. Tropical Journal of Pharmaceutical Research 7(3): 1019-1024.

Azab, A., Nassar, A. & Azab, A.N. 2016. Anti-inflammatory activity of natural products. Molecules 21(10): 1321.

Bhargava, K.K., Dayal, R. & Seshadri, T.R. 1974. Chemical components of Eugenia jambolana stem bark. Current Science 43: 645-646.

Bhatia, I.S. & Bajaj, K.L. 1975. Chemical constituents of the seeds and bark of Syzygium cumini. Planta Medica 28(4): 346-352.

Candy, H.A., McGarry, E.J. & Pegel, K.H. 1968. Constituents of Syzygium cordatum. Phytochemistry 7(5): 889-890.

Carroll, A.R. 2016. Structure revision of four acylphloroglucinols isolated from the leaves of Syzygium polyanthum. Planta Medica Letters 3(1): 8-9.

Chooi, O.H. 2008. Rempah-Ratus: Khasiat Makanan & Ubatan. Kuala Lumpur: Utusan Publications & Distributors Sdn. Bhd.

Dalimartha, S. 2008. Resep Tumbuhan Obat untuk Asam Urat. Depok: Penebar Swadaya.

Dalimartha, S. 2005. Tanaman Obat di Lingkungan Sekitar. Jakarta: Puspa Swara.

Djoukeng, J.D., Abou-Mansour, E., Tabacchi, R., Tapondjou, A.L., Bouda, H. & Lontsi, D. 2005. Antibacterial triterpenes from Syzygium guineense (Myrtaceae). Journal of Ethnopharmacology 101(1-3): 283-286.

Ghosh, J. & Sil, P.C. 2013. Arjunolic acid: A new multifunctional therapeutic promise of alternative medicine. Biochimie 95(6): 1098-1109.

Govaerts, R., Sobral, M., Ashton, P., Barrie, F., Holst, B.K., Landrum, L.L., Matsumoto, K., Mazine, F.F., Lughadha, E.N., Proenca, C. & Soares-Silva, L.H. 2008. World Checklist of Myrtaceae. Richmond: Kew Publishing.

Halliwell, B. & Gutteridge, J.M.C. 2007. Free Radicals in Biology and Medicine. 4th ed. Oxford: Clarendon Press.

Har, L.W., Shaari, K., Boon, L.H., Kamarulzaman, F.A. & Ismail, I.S. 2012. Two new phloroglucinol derivatives and five photosensitizing pheophorbides from Syzygium polyanthum leaves (salam). Natural Product Communications 7(8): 1033-1036.

Hembing, W. 2004. Bebas Diabetes Mellitus Ala Hembing. Jakarta: Puspa Swara.

HPTLC Association. 2012. Standard Operating Procedure for HPTLC. http://www.hptlc-association.org. Accessed on 10 June 2014.

Huang, L.J., Gao, W.Y., Li, X., Zhao, W.S., Huang, L.Q. & Liu, C.X. 2010. Evaluation of the in vivo anti-inflammatory effects of extracts from Pyrus bretschneideri Rehd. Journal of Agricultural and Food Chemistry 58(16): 8983-8987.

Hutton, W. 2003. Handy Pocket Guide to Asian Herbs & Spices. Singapore: Periplus Editions (HK) Ltd.

Jalil, J., Sabandar, C.W., Ahmat, N., Jamal, J.A., Jantan, I., Aladdin, N.A., Muhammad, K., Buang, F., Mohamad, H.F. & Sahidin, I. 2015. Inhibitory effect of triterpenoids from Dillenia serrata (Dilleniaceae) on prostaglandin E₂ production and quantitative HPLC analysis of its koetjapic and betulinic acid contents. Molecules 20(2): 3206-3220.

Kashiwada, Y., Wang, H.K., Nagao, T., Kitanaka, S., Yasuda, I., Fujioka, T., Yamagishi, T., Cosentino, L.M., Kozuka, M., Okabe, H., Ikeshiro, Y., Hu, C.Q., Yeh, E. & Lee, K.H. 1998. Anti-AIDS agents. 30. Anti-HIV activity of oleanolic acid, pomolic acid, and structurally related triterpenoids. Journal of Natural Products 61(9): 1090-1095.

Kato, E., Nakagomi, R., Gunawan-Puteri, M.D.P.T. & Kawabata, J. 2013. Identification of hydroxychavicol and its dimmers, the lipase inhibitors contained in the Indonesian spice, Eugenia polyantha. Food Chemistry 136(3-4): 1239-1242.

Kihampa, C., Nkunya, M.H.H., Joseph, C.C., Magesa, S.M., Hassanali, A., Heydenreich, M. & Kleinpeter, E. 2009. Anti-mosquito and antimicrobial nor-halimanoids, isocoumarins and an anilinoid from Tessmannia densiflora. Phytochemistry 70(10): 1233-1238.

Kijjoa, A., Gonzalez, M.J.T.G., Pinto, M.M.M., Monanondra, I.O. & Herz, W. 1991. Constituents of Knema laurina and Knema tenuinervia ssp. setosa. Planta Medica 57(6): 575-577.

Kim, J.S., Kim, J.C., Shim, S.H., Lee, E.J., Jin, W., Bae, K., Son, K.H., Kim, H.P., Kang, S.S. & Chang, H.W. 2006. Chemical constituents of the root of Dystaenia takeshimana and their anti-inflammatory activity. Archives of Pharmacal Research 29(8): 617-623.

Kurniawati, N. 2010. Sehat dan Cantik Alami Berkat: Khasiat Bumbu Dapur. Bandung: Qanita.

Lelono, R.A.A. & Tachibana, S. 2013a. Bioassay-guided isolation and identification of antioxidative compounds from the bark of Eugenia polyantha. Pakistan Journal of Biological Sciences 16(16): 812-818.

Lelono, R.A.A. & Tachibana, S. 2013b. Preliminary studies of Indonesian Eugenia polyantha leaf extracts as inhibitors of key enzymes for type 2 diabetes. Journal of Medical Sciences 13(2): 103-110.

Lelono, R.A.A., Tachibana, S. & Itoh, K. 2009. In vitro antioxidative activities and polyphenol content of Eugenia polyantha Wight grown in Indonesia. Pakistan Journal of Biological Science 12(24): 1564-1570.

López-Alarcón, C. & Denicola, A. 2013. Evaluating the antioxidant capacity of natural products: A review on chemical and cellular-based assays. Analytica Chimica Acta 763: 1-10.

Lv, H., Qi, Z., Wang, S., Feng, H., Deng, X. & Ci, X. 2017. Asiatic acid exhibits anti-inflammatory and antioxidant activities against lipopolysaccharide and D-galactosamine-induced fulminant hepatic failure. Frontiers in Immunology 8(1): 785.

Mahmoud II, Marzouk, M.S.A., Moharram, F.A., El-Gindi, M.R. & Hassan, A.M.K. 2001. Acylated flavonol glycosides from Eugenia jambolana leaves. Phytochemistry 58(8): 1239-1244.

Manna, P., Sinha, M. & Sil, P.C. 2007. Protection of arsenic-induced hepatic disorder by arjunolic acid. Basic and Clinical Pharmacology and Toxicology 101(5): 333-338.

Mavar-Manga, H., Haddad, M., Pieters, L., Baccelli, C., Penge, A. & Quetin-Leclercq, J. 2008. Anti-inflammatory compounds from leaves and root bark of Alchornea cordifolia (Schumach. & Thonn.) Müll. Arg. Journal of Ethnopharmacology 115(1): 25-29.

Nobakht, G.M., Kadir, M.A. & Stanslas, J. 2010. Analysis of preliminary phytochemical screening of Typhonium flagelliforme. African Journal of Biotechnology 9(11): 1655-1657.

Pairet, M., VanRyn, J., Mauz, A., Schierok, H., Diederen, W., Türck, D. & Engelhardt, G. 1998. Differential inhibition of COX-1 and COX-2 by NSAIDs: A summary of results obtained using various test systems. In Selective COX-2 Inhibitors: Pharmacology, Clinical Effects and Therapeutical Potential, edited by Vane, J. & Botting, J. London: Kluwer Academic Press and William Harvey Press. pp. 27-46.

Parnell, J.A.N., Craven, L.A. & Biffin, E. 2007. Matters of scale: Dealing with one of the largest genera of angiosperms. In Reconstructing the Tree of Life: Taxonomy and Systematics of Species Rich Taxa, edited by Hodkinson, T.R. & Parnell, J.A.N. Florida: CRC Press, Taylor & Francis Group. pp. 251-277.

Patria, T.K. 2016. Sehat dan Cantik Alami dari Dapur. Surabaya: Pandu Media.

Patrignani, P., Panara, M.R., Greco, A., Fusco, O., Natoli, C., Iacobelli, S., Cipollone, A., Ganci, A., Créminon, C. & Maclouf, J. 1994. Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. Journal of Pharmacology and Experimental Therapeutics 271(3): 1705-1712.

Perera, P., Ringbom, T., Huss, U., Vasӓnge, M. & Bohlin, L. 2001. Search for natural products which affect cyclooxygenase-2. In Bioactive Compounds from Natural Sources: Isolation, Characterisation and Biological Properties. London: CRC Press, Taylor & Francis. pp. 433-472.

Quattrocchi, U.F.L.S. 2012. CRC World Dictionary of Medicinal and Poisonous Plants. New York: CRC Press, Taylor & Francis Group. p. 3960.

Renfrew, J.M. & Sanderson, H. 2005. Herbs and Vegetables. In The Cultural History of Plants, edited by Prance, S.G. & Nesbitt, M. New York: Routledge, Taylor & Francis Group. pp. 97-131.

Sabandar, C.W., Jalil, J., Ahmat, N. & Aladdin, N.A. 2019. Assessment of antioxidant and xanthine oxidase inhibitory activity of Triadica cochinchinensis stem bark. Current Research on Biosciences and Biotechnology 1(1): 39-44.

Saifudin, A., Tanaka, K., Kadota, S. & Tezuka, Y. 2012. Protein tyrosine phosphatase 1B (PTP1B)-inhibiting constituents from the leaves of Syzygium polyanthum. Planta Medica 78(12): 1378-1381.

Seidel, V. 2006. Initial and bulk extraction. In Natural Products Isolation: Methods in Biotechnology, edited by Sarker, S.D., Latif, Z. & Gray, A.I. Totowa: Humana Press. pp. 27-46.

Shahidi, F. & Zhong, Y. 2015. Measurement of antioxidant activity. Journal of Functional Foods 18(B): 757-781.

Srivastava, R., Shaw, A. & Kulshreshtha, D.K. 1995. Triterpenoids and chalcone from Syzygium samarangense. Phytochemistry 38(3): 687-689.

The Plant List. 2013. The Plant List Version 1.1. 2013. http://www.theplantlist.org/ Accessed on 3 October 2019.

Vane, J.R. & Botting, R.M. 1996. Formation and actions of prostaglandins and inhibitors of their synthesis. In Therapeutic Roles of Selective COX-2 Inhibitors. London: William Harvey Press.

Willcox, J.K., Ash, S.L. & Catignani, G.L. 2004. Antioxidants and prevention of chronic disease. Critical Reviews in Food Science and Nutrition 44(4): 275-295.

Wilson, P.G. 2011. Myrtaceae. In The Families and Genera of Vascular Plants, Flowering Plants, Eudicots: Sapindales, Cucurbitales, Myrtaceae, edited by Kubitski, K. Germany: Springer-Verlag. pp. 212-271.

Yin, H., Zhang, S., Wu, J. & Nan, H. 2006. Dihydropyranoflavones from Pongamia pinnata. Journal of the Brazilian Chemical Society 17(7): 1432-1435.

Yun, K.J., Kim, J.Y., Kim, J.B., Lee, K.W., Jeong, S.Y., Park, H.J., Jung, H.J., Cho, Y.W., Yun, K. & Lee, K.T. 2008. Inhibition of LPS-induced NO and PGE₂ production by asiatic acid via NF-κB inactivation in RAW 264.7 macrophages: Possible involvement of the IKK and MAPK pathways. International Immunopharmacology 8(3): 431-441.

Zhou, J., Xie, G. & Yang, X. 2011. Encyclopedia of Traditional Chinese Medicines: Molecular Structures, Pharmacological Activities, Natural Sources and Applications. Vol. 2. Heidelberg: Springer. pp. 1-601.

^*Corresponding author; email: juriyatijalil@ukm.edu.my