Antidiabetic potential of phytochemicals isolated from the stem bark of Myristica fatua Houtt. var. magnifica (Bedd.) Sinclair

B Prabha; S Neethu; S Lekshmy Krishnan; D R Sherin; M Madhukrishnan; R Ananthakrishnan; K B Rameshkumar; T K Manojkumar; P Jayamurthy; K V Radhakrishnan

doi:10.1016/j.bmc.2018.05.020

Antidiabetic potential of phytochemicals isolated from the stem bark of Myristica fatua Houtt. var. magnifica (Bedd.) Sinclair

Bioorg Med Chem. 2018 Jul 23;26(12):3461-3467. doi: 10.1016/j.bmc.2018.05.020. Epub 2018 May 19.

Authors

Affiliations

¹ Chemical Science and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram 695019, India.
² Chemical Science and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram 695019, India; Academy of Scientific and Innovative Research (AcSIR), Thiruvananthapuram 695019, India.
³ Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram 695019, India.
⁴ Centre for Computational Modeling and Data Engineering, Indian Institute of Information Technology and Management, Thiruvananthapuram 695581, India.
⁵ Phytochemistry Division, Jawaharlal Nehru Tropical Botanic Garden and Research Institute, Palode, Thiruvananthapuram 695562, India.
⁶ Academy of Scientific and Innovative Research (AcSIR), Thiruvananthapuram 695019, India; Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram 695019, India.
⁷ Chemical Science and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram 695019, India; Academy of Scientific and Innovative Research (AcSIR), Thiruvananthapuram 695019, India. Electronic address: radhu2005@gmail.com.

PMID: 29789207
DOI: 10.1016/j.bmc.2018.05.020

Abstract

Phytochemical investigation of the stem bark of Myristica fatua Houtt. led to the isolation of a new compound 1 (3-tridecanoylbenzoic acid), along with six known acylphenols (2-7). All the compounds displayed moderate inhibitory activity on α-amylase and significant activity on α-glucosidase; however malabaricone B (6) and C (7) were identified as potent α-glucosidase inhibitors with IC₅₀ values of 63.70 ± 0.546, and 43.61 ± 0.620 µM respectively. Acylphenols (compounds 3-7) also showed significant antiglycation property. The molecular docking and dynamics simulation studies confirmed the efficient binding of malabaricone C with C-terminus of human maltase-glucoamylase (2QMJ). Malabaricone B also enhanced the 2-NBDG [2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy glucose] uptake in L6 myotubes. These findings demonstrate that acylphenols isolated from Myristica fatua Houtt. can be considered as a lead scaffold for the treatment of type II diabetes mellitus.

Keywords: Glucose uptake in L6 myotubes; Myristica fatua Houtt; Protein glycation; Simulation studies; α-Amylase; α-Glucosidase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Cell Line
Cell Survival / drug effects
Diabetes Mellitus, Type 2 / drug therapy
Diabetes Mellitus, Type 2 / pathology
Glycoside Hydrolase Inhibitors / chemistry*
Glycoside Hydrolase Inhibitors / metabolism
Glycoside Hydrolase Inhibitors / pharmacology
Humans
Hypoglycemic Agents / chemistry*
Hypoglycemic Agents / metabolism
Hypoglycemic Agents / pharmacology
Hypoglycemic Agents / therapeutic use
Molecular Dynamics Simulation
Muscle Cells / cytology
Muscle Cells / drug effects
Muscle Cells / metabolism
Myristicaceae / chemistry*
Myristicaceae / metabolism
Phytochemicals / chemistry*
Phytochemicals / metabolism
Phytochemicals / pharmacology
Plant Bark / chemistry
Plant Bark / metabolism
Plant Extracts / chemistry
Plant Stems / chemistry
Plant Stems / metabolism
Protein Structure, Tertiary
Resorcinols / chemistry
Resorcinols / metabolism
Resorcinols / pharmacology
alpha-Glucosidases / chemistry
alpha-Glucosidases / metabolism

Substances

Glycoside Hydrolase Inhibitors
Hypoglycemic Agents
Phytochemicals
Plant Extracts
Resorcinols
malabaricone B
malabaricone C
alpha-Glucosidases