Sains Malaysiana 51(1)(2022): 199-208

http://doi.org/10.17576/jsm-2022-5101-16

Deciphering Synsepalum dulcificum as an Arising Phytotherapy Agent: Background, Phytochemical and Pharmacological Properties with Associated Molecular Mechanisms

(Mentafsir Synsepalum dulcificum sebagai Agen Fitoterapi yang semakin Meningkat: Latar Belakang, Sifat Fitokimia dan Farmakologi dengan Mekanisme Molekul Berkaitan)

JIA WER EE¹, APPALARAJU VELAGA¹, RHANYE MAC GUAD², VETRISELVAN SUBRAMANIYAN³, NEERAJ KUMAR FULORIA⁴, SHIVKANYA FULORIA⁴, KER WOON CHOY⁵& YUAN SENG WU^6,7*

¹Department of Medicinal Chemistry, Faculty of Pharmacy, MAHSA University, 42610 Jenjarom, Selangor Darul Ehsan, Malaysia

²Department of Biomedical Science and Therapeutics, Faculty of Medicine and Health Science, Universiti Malaysia Sabah, 88400 Kota Kinabalu, Sabah, Malaysia

³Department of Pharmacology, School of Medicine, Faculty of Medicine, Bioscience and Nursing, MAHSA University, 42610 Jenjarom, Selangor Darul Ehsan, Malaysia

⁴Faculty of Pharmacy, AIMST University, 08100 Bedang, Kedah Darul Aman, Malaysia

⁵Department of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, 47000 Sungai Buloh, Selangor Darul Ehsan, Malaysia

⁶Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia

⁷Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia

Diserahkan: 25 November 2020/Diterima: 19 Mei 2021

ABSTRACT

Medicinal plants with less side effects are paramount important for humankind to cure various ailments as compared to newly developed allopathic medicines. Synsepalum dulcificum Daniell, (Sapotaceae), is well known as miracle fruits due to its distinctive taste-modifying property. This review aimed to discuss its recent reported pharmacological properties and associated molecular mechanisms as a novel phytotherapy agent. In addition, background, phytochemical analysis and toxicological studies were also discussed as the foundation and added values for this review. It was discovered that S. dulcificum is endowed with various classes of phytochemicals, such as flavonoids, tannins, alkaloids and saponins. This review ravelled that S. dulcificum is a potent medicinal plant associated with antioxidant, antidiabetic, antimicrobial, anticancer, anti-hyperuricemic, hepatoprotective, anti-hyperlipidaemic, and anticonvulsant activities, with less toxicity shown. Future research may explore further the corresponding phytochemicals, associated molecular mechanisms, toxicological and pharmacokinetic profile before subjecting to clinical testing.

Keywords: Miracle fruit; molecular mechanism; phytotherapy agent; Synsepalum dulcificum; therapeutic activity

ABSTRAK

Tumbuhan perubatan sangat penting bagi manusia untuk menyembuhkan pelbagai penyakit berbanding dengan ubat aloi yang baru dikembangkan kerana ia lebih selamat dengan kesan sampingan yang lebih rendah. Synsepalum dulcificum Daniell, (Sapotaceae), terkenal sebagai buah ajaib kerana sifatnya yang mengubah rasa. Ulasan ini bertujuan untuk meninjau dan menguraikan sifat farmakologi yang dilaporkan baru-baru ini dan mekanisme molekul yang berkaitan sebagai agen fitoterapi baru. Selain itu, latar belakang, analisis fitokimia dan kajian toksikologi juga dibincangkan sebagai asas dan nilai tambah untuk ulasan ini. S. dulcificum didapati dikurniakan pelbagai kelas fitokimia, seperti flavonoid, tanin, alkaloid dan saponin. Ulasan ini membuktikan bahawa S. dulcificum adalah tumbuhan perubatan kuat yang memiliki aktiviti antioksidan, antidiabetik, antimikrob, antikanser, anti-hiperurikemia, hepatopelindung, anti-hiperlipidemia dan antikonvulsan dengan ketoksikan yang kurang ditunjukkan. Penyelidikan masa depan boleh mengkaji fitokimia, mekanisme molekul yang berkaitan, profil toksikologi dan farmakokinetik sebelum menjalani ujian klinikal.

Kata kunci: Agen fitoterapi; aktiviti terapi; buah keajaiban; mekanisme molekul; Synsepalum dulcificum

RUJUKAN

Achigan-Dako, E.G., Tchokponhoué, D.A., N’Danikou, S., Gebauer, J. & Vodouhè, R.S. 2015. Current knowledge and breeding perspectives for the miracle plant Synsepalum dulcificum (Schum. et Thonn.) Daniell. Genetic Resources and Crop Evolution 62(3): 465-476.

Akinmoladun, A.C. 2016. Effect of Synsepalum dulcificum berry extracts on oxidative stress and hepatotoxicity indices, following subacute administration in normal rats. Futa Journal of Research in Sciences 1: 167-177.

Awotedu, O.L. & Ogunbamowo, P.O. 2019a. Pharmacognostic and physicochemical profile of the leaves of Synsepalum dulcificum (Schumach. & Thonn.) Daniell. International Journal of Agriculture, Forestry and Fisheries 7(2): 12-17.

Awotedu, O.L. & Ogunbamowo, P.O. 2019b. Nutritional, anti-nutritional and phytochemical profile of the leaves and fruits of Synsepalum dulcificum (Schumach. & Thonn.) Daniell. American Journal of Biological Chemistry 7(3): 53-59.

Bhatia, H., Sharma, Y.P., Manhas, R.K. & Kumar, K. 2014. Ethnomedicinal plants used by the villagers of district Udhampur, J&K, India. Journal of Ethnopharmacology 151(2): 1005-1018.

Bonam, S.R., Wu, Y.S., Tunki, L., Chellian, R., Halmuthur, M.S.K., Muller, S. & Pandy, V. 2018. What has come out from phytomedicines and herbal edibles for the treatment of cancer? ChemMedChem 13(18): 1854-1872.

Brand-Williams, W., Cuvelier, M.E. & Berset, C. 1995. Use of a free radical method to evaluate antioxidant activity. LWT - Food Science and Technology 28(1): 25-30.

Buckmire, R.E. & Francis, F.J. 1978. Pigments of miracle fruit, Synsepalum dulcificum, schum, as potential food colorants. Journal of Food Science 43(3): 908-911.

Chen, C.Y., Wu, P.Y., Huang, T.S., Lin, C.W., Li, Y.C., Chou, R.H., Chang, H.W. & Wang, H.M. 2009. The sour taste-modifying protein (miraculin), tyrosinase inhibitors and antioxidants from Synsepalum dulcificum. Current Nutrition & Food Science 5(3): 172-179.

Cheng, F.Y., Huang, S.T., Lin, M.L. & Lai, J.T. 2015. Polyphenol measurement and antioxidant activity of miracle fruit. International Journal of Chemical Engineering and Applications 6(3): 211-214.

Chinelo, C. & Uzoma, N.O. 2015. Effect of methanol extract of Synsepalum dulcificum pulp on some biochemical parameters in albino rats.  Journal of Coastal Life Medicine 3(3): 233-240.

Dioso, M.K.M., Satsatin, D.C.A. & Ching, J.A. 2016. Hypoglycemic effects of Synsepalum dulcificum (Schumach. and Thonn.) Daniell (MiracleBerry) fruit and leaf extracts on the blood glucose level of albino rats.  Der Pharmacia Letter 8(14): 104-108.

Duke, J.A. 1993. CRC Handbook of Alternative Cash Crops. Boca Raton: CRC Press.

Du, L., Shen, Y., Zhang, X., Prinyawiwatkul, W. & Xu, Z. 2014. Antioxidant-rich phytochemicals in miracle berry (Synsepalum dulcificum) and antioxidant activity of its extracts. Food Chemistry 153: 279-284.

Han, Y.C., Wu, J.Y. & Wang, C.K. 2019. Modulatory effects of miracle fruit ethanolic extracts on glucose uptake through the insulin signaling pathway in C2C12 mouse myotubes cells. Food Science & Nutrition 7(3): 1035-1042.

Huang, W., Chung, H.Y., Xuan, W., Wang, G. & Li, Y. 2020. The cholesterol-lowering activity of miracle fruit (Synsepalum dulcificum). Journal of Food Biochemistry 44(5): 1-12.

Inglett, G.E. & Chen, D. 2011. Contents of phenolics and flavonoids and antioxidant activities in skin, pulp, and seeds of miracle fruit. Journal of Food Science 76(3): 479-482.

Inglett, G.E. & May, J.F. 1968. Tropical plants with unusual taste properties. Economic Botany 22(4): 326-331.

Inglett, G.E., Dowling, B., Albrecht, J.J. & Hoglan, F.A. 1965. Taste modifiers, taste-modifying properties of miracle fruit (Synsepalum dulcificum). Journal of Agricultural and Food Chemistry 13(3): 284-287.

Jeremiah, O.J., Ilesanmi, O.R. & Ige, M.M. 2015. Evaluation of the anticonvulsant potential of aqueous fraction of Synsepalum dulcificum seed extract in mice. European Journal of Medicinal Plants 9(3): 1-8.

Joyner, G. 2006. The miracle fruit. In Quandong Magazine of the West Australian Nut and Tree Crop Association, edited by Scott, P. West  Australia: West  Australian  Nut and  Tree  Crop  Association  Subiaco. p. 15.

Kumar, D.R.N., Cijo George, V., Suresh, P.K. & Ashok Kumar, R. 2012. Cytotoxicity, apoptosis induction and anti-metastatic potential of Oroxylum indicum in human breast cancer cells. Asian Pacific Journal of Cancer Prevention 13(6): 2729-2734.

Lim, T.K. 2013. Synsepalum dulcificum. In Edible Medicinal and Non-Medicinal Plants: Volume 6, Fruits edited by Lim, T.K. Netherlands: Springer. pp. 146-150.

Lu, S.L., Liu, H., Chen, G.Y., Han, C.R. & Zang, W.X. 2014. Chemical composition of leaf essential oil of Synsepalum dulcificum and evaluation of its antibacterial and antitumoral activities in vitro. Chemistry and Industry of Forest Products 34(1): 121-127.

Mahady, G.B. 2001. Global harmonization of herbal health claims. The Journal of Nutrition 131(3): 1120S-1123S.

Njoku, N.E., Ubbaonu, C.N., Alagbaoso, S.O., Agunwa, I.M. & Eluchie, C.N. 2016. Proximate, anti-nutritional and phytochemical composition of the yellow variety of the Synsepalum dulcificum (miracle fruit) berry. American Journal of Food Science and Technology 4(4): 102-108.

Obafemi, T.O., Olaleye, M.T. & Akinmoladun, A.C. 2019. Antidiabetic property of miracle fruit plant (Synsepalum dulcificum Shumach. & Thonn. Daniell) leaf extracts in fructose-fed streptozotocin-injected rats via anti-inflammatory activity and inhibition of carbohydrate metabolizing enzymes. Journal of Ethnopharmacology 244(112124): 1-8.

Obafemi, T.O., Akinmoladun, A.C., Olaleye, M.T., Agboade, S.O. & Onasanya, A.A. 2017. Antidiabetic potential of methanolic and flavonoid-rich leaf extracts of Synsepalum dulcificum in type 2 diabetic rats. Journal of Ayurveda and Integrative Medicine 8(4): 238-246.

Osabor, V.N., Etiuma, R.A. & Ntinya, M.U. 2016. Chemical profile of leaves and roots of miracle fruits (Synsepalum dulcificum). American Chemical Science Journal 12(1): 1-8.

Oumorou, M., Dah-Dovonon, J., Aboh, B.A., Hounsoukaka, M. & Sinsin, B. 2010. Contribution a` la conservation de synsepalum dulcificum: re´ge´ne´ration et importance socioe´conomique dans le de´partement de l’oue´me´ (Benin). Ann. Sci. Agron. 14(1): 101-120.

Philippine Medicinal Plants (PMP). 2018. Miracle fruit, Synsepalum dulcificum (Schumach. & Thonn). http://www.stuartxchange.org/MiracleFruit. Accessed on 13 September 2020.

Rahmani, A.H. & Aldebasi, Y.H. 2015. Potential role of Carica papaya and their active constituents in the prevention and treatment of diseases. International Journal of Pharmacy and Pharmaceutical Sciences 8(1): 11-15.

Ramakrishnan, P., Loh, W.M., Gopinath, S.C.B., Bonam, S.R., Fareez, I.M., Guad, R.M., Sim, M.S. & Wu, Y.S. 2020. Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer. Acta Pharmaceutica Sinica B 10(3): 399-413.

Seong, J., Oyong, G. & Cabrera, E. 2018. Synsepalum dulcificum extracts exhibit cytotoxic activity on human colorectal cancer cells and upregulate c-fos and c-jun early apoptotic gene expression. Asian Pacific Journal of Tropical Biomedicine 8(3): 173-178.

Shi, Y.C., Lin, K.S., Jhai, Y.F., Lee, B.H., Han, Y., Cui, Z., Hsu, W.H. & Wu, S.C. 2016. Miracle fruit (Synsepalum dulcificum) exhibits as a novel anti-hyperuricaemia agent. Molecules 21(2): 1-11.

Small, E. & Catling, P.M. 2006. Blossoming treasures of biodiversity. Biodiversity 7(3-4): 37-46.

Soares, H.P., Cusnir, M., Schwartz, M.A., Pizzolato, J.F., Lutzky, J., Campbell, R.J., Beaumont, L., Eton, D., Stonick, S. & Lilenbaum, R. 2010. Treatment of taste alterations in chemotherapy patients using the “miracle fruit”: Preliminary analysis of a pilot study. Journal of Clinical Oncology 28(15_suppl): e19523.

Soladoye, M.O. & Chukwuma, E.C. 2012. Quantitative phytochemical profile of the leaves of Cissus populnea Guill. and Perr. (Vitaceae) â an important medicinal plant in central Nigeria. Archives of Applied Science Research 4(1): 200-206.

Swamy, K.B., Hadi, S.A., Sekaran, M. & Pichika, M.R. 2014. The clinical effects of Synsepalum dulcificum: A review. Journal of Medicinal Food 17(11): 1165-1169.

Wang, C.Z., Calway, T. & Yuan, C.S. 2012. Herbal medicines as adjuvants for cancer therapeutics. The American Journal of Chinese Medicine 40(4): 657-669.

Wasoh, H., Tajuddin, S., Halim, M., Mohd-Hairul, A.R., Sobri, M.Z.M., Lajis, A.F.B., Yusof, M.T. & Ariff, A.B. 2018. Antibacterial activity of Synsepalum dulcificum leaf extract against Listeria monocytogenes and its comparison with Strobilanthes crispus and Morus alba. Journal of Bio-Science 25: 73-75.

Wilken, M.K. & Satiroff, B.A. 2012. Pilot study of "miracle fruit" to improve food palatability for patients receiving chemotherapy. Clinical Journal of Oncology Nursing 16(5): E173-177.

Yin, X., Zhou, J., Jie, C., Xing, D. & Zhang, Y. 2004. Anticancer activity and mechanism of Scutellaria barbata extract on human lung cancer cell line A549. Life Sciences 75(18): 2233-2244.

*Pengarang untuk surat-menyurat; email: sengwu_21@yahoo.com