PMID- 34508803 OWN - NLM STAT- MEDLINE DCOM- 20220207 LR - 20220207 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 282 DP - 2022 Jan 10 TI - alpha-glucosidase inhibitors from Syzygium polyanthum (Wight) Walp leaves as revealed by metabolomics and in silico approaches. PG - 114618 LID - S0378-8741(21)00847-3 [pii] LID - 10.1016/j.jep.2021.114618 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium polyanthum (Wight) Walp leaves are traditionally used to cure diabetes in many regions of Indonesia. Traditional use involves boiling the leaves until the water is reduced to half volume, and then the decoction is taken 1-2 times daily. Despite several studies reporting the antidiabetic activity of this plant, bioactive compounds have not been well identified. AIM OF THE STUDY: Indonesia is one of the countries with the highest diabetes cases, particularly type 2 diabetes mellitus (T2DM). Few people have access to modern medicinal treatment; thus, the role of antidiabetic traditional medicine has become increasingly important. This research aimed to identify alpha-glucosidase inhibitors from S. polyathum leaves using a metabolomics approach. When the active compounds of S. polyathum are properly identified, the quality of the herb can be more easily controlled. MATERIALS AND METHODS: The dried leaves of S. polyanthum were extracted by a comprehensive extraction method using a solvent combination of n-hexane, acetone, and water in a gradient, resulting in a total of 42 fractions. All fractions were subjected to an in vitro alpha-glucosidase inhibition test and chemical profile analysis using Nuclear Magnetic Resonance (NMR) and high performance liquid chromatography (HPLC). Orthogonal projection least square (OPLS) analysis was used to correlate the two data to identify NMR signals, and HPLC chromatogram peaks correlated to the activity. 2D NMR and ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) analyses were also used to give more precise compound identification. The activity of the identified active compounds was confirmed by an in silico technique. RESULTS AND DISCUSSION: The results of the alpha-glucosidase activity test showed that the most active fractions were obtained from solvents with medium polarity: Fractions 9 and 10 (F9 and F10), obtained from gradient acetone-water 4:1 and 3:2, respectively. The IC50 values of F9 and F10 were 24.8 and 31.8 mug/mL, respectively. NMR data showed that F9 had more intense and diverse signals in the aromatic region than F10. OPLS analysis results showed that some typical flavonoid signals abundant in F9 positively correlated with alpha-glucosidase activity. 2D NMR and UHPLC-HRMS analysis of F9 led to the conclusion that these signals could be attributed to myricetin-3-O-rhamnoside (myricitrin) and epigallocatechin-3-gallate (EGCG). In silico analysis confirmed these results, as myricitrin and EGCG had binding energies resembling acarbose as a positive control (-8.47, -8.19, and -10.13, respectively). CONCLUSIONS: NMR and HPLC-metabolomics successfully identified myricitrin and EGCG as alpha-glucosidase inhibitors from S. polyanthum leaves, and docking analysis validated their inhibitory activity. The results of this study justified the traditional use of S. polyanthum as an antidiabetes herbal. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Syabana, Mohamad Ana AU - Syabana MA AD - Department of Food Science and Technology, IPB Dramaga Campus, IPB University, Bogor, Indonesia; Department of Food Technology and Center of Excellence for Local Food Innovation, Sultan Ageng Tirtayasa University, Serang, Indonesia. FAU - Yuliana, Nancy Dewi AU - Yuliana ND AD - Department of Food Science and Technology, IPB Dramaga Campus, IPB University, Bogor, Indonesia; Tropical Biopharmaca Research Center, IPB University, Bogor, Indonesia; Halal Science Center, IPB University, Bogor, Indonesia. Electronic address: nancy_dewi@apps.ipb.ac.id. FAU - Batubara, Irmanida AU - Batubara I AD - Department of Chemistry, IPB University, Bogor, Indonesia; Tropical Biopharmaca Research Center, IPB University, Bogor, Indonesia. FAU - Fardiaz, Dedi AU - Fardiaz D AD - Department of Food Science and Technology, IPB Dramaga Campus, IPB University, Bogor, Indonesia. LA - eng PT - Journal Article DEP - 20210909 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Glycoside Hydrolase Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Plant Extracts) RN - EC 3.2.1.20 (alpha-Glucosidases) SB - IM MH - Glycoside Hydrolase Inhibitors/*pharmacology MH - Hypoglycemic Agents/chemistry/pharmacology MH - *Metabolomics MH - *Molecular Docking Simulation MH - Phytotherapy MH - Plant Extracts/chemistry/*pharmacology MH - Plant Leaves/*chemistry MH - Structure-Activity Relationship MH - Syzygium/*chemistry MH - alpha-Glucosidases/metabolism OTO - NOTNLM OT - Antidiabetes OT - Epigallocatechin-3-gallate OT - Myricitrin OT - OPLS OT - Salam leaves EDAT- 2021/09/12 06:00 MHDA- 2022/02/08 06:00 CRDT- 2021/09/11 20:09 PHST- 2021/04/30 00:00 [received] PHST- 2021/08/20 00:00 [revised] PHST- 2021/09/07 00:00 [accepted] PHST- 2021/09/12 06:00 [pubmed] PHST- 2022/02/08 06:00 [medline] PHST- 2021/09/11 20:09 [entrez] AID - S0378-8741(21)00847-3 [pii] AID - 10.1016/j.jep.2021.114618 [doi] PST - ppublish SO - J Ethnopharmacol. 2022 Jan 10;282:114618. doi: 10.1016/j.jep.2021.114618. Epub 2021 Sep 9.