Identification of Dipeptidyl-Peptidase 4 (DPP-4) Inhibitors from Miracle Berry Fruit (Synsepalum dulcificum) Extract
DOI:
https://doi.org/10.54987/jobimb.v11i1.805Abstract
Dipeptidyl-peptidase 4 is a novel targeted enzyme in type 2 diabetes mellitus (T2DM) therapy due to its regulatory effect on incretin; glucagon-like peptide 1 (GLP-1) that responsible for stimulating insulin and suppressing glucagon secretion. DPP-4 degrades GLP-1 to biologically inactive fragments. In incretin-based therapies, DPP-4 inhibitor helps to restrain the inactivation of GLP-1, which in turn prolonging GLP-1’s half-life in blood and subsequently reducing the blood sugar more effectively. Nowadays, researchers are focusing to replace the synthetic drugs with natural-based drugs since they exert less toxicity. In our attempt to discover the natural inhibitor for DPP-4, miracle berry fruit was sequentially extracted with different solvents such as hexane, dichloromethane, chloroform, ethyl acetate and methanol and screened for the DPP-4 inhibitory activity. The analyses on the extractions show dichloromethane yielded the highest number of phenolic compounds with 38.37 mg GAE/g, while the highest number of flavonoids was found in hexane extract with 142.269 mg QE/g. On the other hand, qualitative analyses showed that methanol was able to extract alkaloids, terpenoids, saponins, tannins, quinones and carbohydrate from miracle berry fruit. It was also found that ethyl acetate extract was able to completely inhibit the enzyme. For further identification of constituent responsible for DPP-4 inhibitory activity, ethyl acetate extract was then subjected to silica gel column chromatography and eluted with different solvents with increasing polarity. The active fraction was then subjected to LC-MS/MS analysis and the results show it contains astragalin, nialamide, n-acetyl-l-phenylalanine, (+)-6-gingerol, 9-nitro oleate and 4(3H)-quinazolinone. The study indicates that miracle berry fruit extract contains natural DPP-4 inhibitor that can potentially be used for treating T2DM.
References
Baggio LL, Drucker DJ. Biology of Incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131-57.
Scheen AJ. Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010;12(8):648-58.
Huang J, Jia Y, Sun S, Meng L. Adverse event profiles of dipeptidyl peptidase-4 inhibitors: Data mining of the public version of the FDA adverse event reporting system. BMC Pharmacol Toxicol. 2020;21(1).
Zarib ANM, Zollappi ANH, Abidin MZ, Rahim MBHA, Gani SA, Hamid M, et al. Total phenolic, total flavonoid and antioxidant activity of extract from rhizome of cibotium barometz prepared by various solvents. Malays J Biochem Mol Biol. 2018;21(2):17-22.
Abidin MZ, Yatim NLAM, Zollapi NNH, Rahim MBHA, Gani SA, Hamid M, et al. Optimization of ultrasonic-assisted extraction of phenolic compound from golden chicken fern (Cibotium barometz) rhizome via response surface methodology. Malays J Biochem Mol Biol. 2019;22(1):87-92.
Zainudin RF, Abidin MZ, Hamsah Zollappi AN, Mohd Yatim NLA, Tamsir NM, Hamid M, et al. Enhancement of anti-advance glycation end product formation and antioxidant activity of salak peel extracts using betaine-based deep eutectic solvents. Malays J Biochem Mol Biol. 2020;23(2):106-12.
Du L, Shen Y, Zhang X, Prinyawiwatkul W, Xu Z. Antioxidant-rich phytochemicals in miracle berry (Synsepalum dulcificum) and antioxidant activity of its extracts. Food Chem. 2014 Jun;153:279-84.
Sembiring EN, Elya B, Sauriasari R. Phytochemical screening, total flavonoid and total phenolic content and antioxidant activity of different parts of Caesalpinia bonduc (L.) Roxb. Pharmacogn J. 2018;
Chang C chi, Yang M hua, Wen H mei, Chern J chuan. Estimation of Total Flavonoid Content in Propolis by. J Food Drug Anal. 2002;10(3):7802.
Kaczorová D, Karalija E, Dahija S, Bešta-Gajevi? R, Pari? A, ?avar Zeljkovi? S. Influence of extraction solvent on the phenolic profile and bioactivity of two achillea species. Molecules. 2021;26(6):1-15.
Bhebhe M, Füller TN, Chipurura B, Muchuweti M. Effect of Solvent Type on Total Phenolic Content and Free Radical Scavenging Activity of Black Tea and Herbal Infusions. Food Anal Methods. 2016 Apr;9(4):1060-7.
Turkmen N, Velioglu Y, Sari F, Polat G. Effect of Extraction Conditions on Measured Total Polyphenol Contents and Antioxidant and Antibacterial Activities of Black Tea. Molecules. 2007 Mar;12(3):484-96.
Andersen ØM, Markham KR. Chemistry, Biochemistry and Applications Edited by. 2006.
Rodríguez De Luna SL, Ramírez-Garza RE, Serna Saldívar SO. Environmentally Friendly Methods for Flavonoid Extraction from Plant Material: Impact of Their Operating Conditions on Yield and Antioxidant Properties. Sci World J. 2020;2020.
Sri Widyawati P, Dwi Wibawa Budianta T, Anggraeni Kusuma F, Livia Wijaya E. Difference of Solvent Polarity To Phytochemical Content and Antioxidant Activity of Pluchea indicia Less Leaves Extracts. Available Online Wwwijpprcom Int J Pharmacogn Phytochem Res. 2014;6(4).
Dehkharghanian M, Adenier H, Vijayalakshmi MA. Study of flavonoids in aqueous spinach extract using positive electrospray ionisation tandem quadrupole mass spectrometry. Food Chem. 2010 Aug;121(3):863-70.
Gao Y, Zhang Y, Zhu J, Li B, Li Z, Zhu W, et al. Recent progress in natural products as DPP-4 inhibitors. Future Med Chem. 2015 Jun;7(8):1079-89.
Fan J, Johnson MH, Lila MA, Yousef G, de Mejia EG. Berry and Citrus Phenolic Compounds Inhibit Dipeptidyl Peptidase IV: Implications in Diabetes Management. Evid-Based Complement Altern Med ECAM. 2013 Aug;2013:479505.
Tanwar O, Deora GS, Tanwar L, Janardhan S, Alam MM, Shaquiquzzaman M, et al. Novel hydrazine derivatives as selective DPP-IV inhibitors: Findings from virtual screening and validation through molecular dynamics simulations. J Mol Model. 2014;20(4).
Samad M Bin, Mohsin MNA Bin, Razu BA, Hossain MT, Mahzabeen S, Unnoor N, et al. [6]-Gingerol, from Zingiber officinale, potentiates GLP-1 mediated glucose-stimulated insulin secretion pathway in pancreatic ?-cells and increases RAB8/RAB10-regulated membrane presentation of GLUT4 transporters in skeletal muscle to improve hyperglycemi. BMC Complement Altern Med. 2017;17(1):1-13.
Cid-Ortega S, Monroy-Rivera JA. Extraction of kaempferol and its glycosides using supercritical fluids from plant sources: A review. Food Technol Biotechnol. 2018;56(4):480-93.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Journal of Biochemistry, Microbiology and Biotechnology
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
