Insights into the Mechanism of Action of Helianthus annuus (Sunflower) Seed Essential Oil in the Management of Type-2 Diabetes Mellitus Using Network Pharmacology and Molecular Docking Approaches

Abstract

Type-2 diabetes mellitus (T2D) is one of the leading non-communicable diseases of global concern. Knowing the exact mechanism of action of available antidiabetic agents, particularly natural products, may assist in providing effective therapeutic solutions. The antidiabetic action of Helianthus annuus (sunflower) seed has been established; however, the molecular mechanism of action, especially the essential oil, is lacking. The study explored network pharmacology and molecular docking studies to determine the active phytoconstituents, signaling pathways, and probable therapeutic targets to determine the antidiabetic potential of sunflower seed essential oil. Preliminary analysis established 23 target genes with 15 phytoconstituents involved in T2D which all passed Lipinski’s rule of five with no violation. Three pathways were proposed by KEGG analysis as therapeutic targets for T2D development with PPAR as the major route affecting PPARA, FABP4, PPARD, PPARG, and CPT2 genes. Molecular docking investigation confirmed the effectiveness of active SSEO compounds against the identified genes (targets) and established phylloquinone, linoleic acid, tricosylic acid, and lignoceric acid as the probable drug candidates that could offer laudable therapeutic effects in an effort towards T2D management. Thereby, we present an insight toward understanding the mechanism of the antidiabetic action of sunflower seeds via the stimulation of glucose to enhance insulin release.

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“…The network pharmacology approach provides avenues for new drug candidates or secondary metabolites, genetic target profiles, and connected signaling pathways linked to diseases, including infectious and non-infectious ones [30,61], achieved by a number of analyses [25,27,28,30,31]. While the five targets not connected in the PPI network may indicate their lack of involvement in the connectivity of the network, suggesting that they may not necessarily or unlikely be involved in any metabolic pathway or offer any molecular function, the cAMP as a key second messenger in signaling pathways has been reported, particularly in drug development [62], particularly against T2DM [25].…”

“…Identification of target genes related to CS secondary metabolites was performed through employing both Swiss Target Prediction (STP) (http://www.swisstargetprediction.ch/; accessed on 1 August 2022) and Similarity Ensemble Approach (SEA) (https://sea.bkslab.org/; accessed on 1 August 2022) databases to avoid biases, while the T2DM-related target genes were identified from GeneCards database (https://www.genecards.org/; accessed on 1 August 2022). Subsequently, Venny 2.1 (https://bioinfogp.cnb.csic.es/tools/venny/; accessed on 10 August 2022) was employed to identify and characterize the overlapping targets between CS secondary metabolites and T2DM target genes [30].…”

“…Preparation of the T2DM-related target genes was performed using USCF Chimera v 1.16 through the removal of water molecules and protein residue connectivity [44]. Three-dimensional (3D) conformers of the CS secondary metabolites as well as the reference standards metformin and resveratrol were obtained from Pub-Chem (https://pubchem.ncbi.nlm.nih.gov/; accessed on 1 September 2022) as previously reported [30]. The addition of Gasteiger charges and non-polar hydrogen atoms was performed on USCF Chimera v 1.16 for optimization of the 3D conformers [45].…”

“…The interaction between drug targets and multiple components such as proteins, genes, and signaling pathways in a biological system are better explored using NP analysis [25], providing a unique perspective on drug action and disease mechanisms by considering the complexity of biological systems in order to provide insights into drug development and optimization [26]. Interestingly, there have been numerous studies that have investigated the antidiabetic mechanism of action (MoA) of natural products, plants, or plant fractions using NP [19,[27][28][29][30]. Molecular docking is a cost-effective, fast, and reliable computational method, employed in drug discovery, medicinal chemistry, and structural biology, to examine the interactions between a small molecule (ligand) and a target biomolecule, typically a protein [31].…”

Integrating network pharmacology with molecular docking to rationalize the ethnomedicinal use of Alchornea laxiflora (Benth.) Pax & K. Hoffm. for efficient treatment of depression

“…Similarly, network pharmacology has been applied to various complex disease conditions, such as Alzheimer, asthma, atherosclerosis, diabetes mellitus, cancer, COVID-19, etc. ( Batool et al, 2022 ; Zhang Z. et al, 2022 ; Wang et al, 2022 ; Alnusaire et al, 2023 ; Rampadarath et al, 2023 ; Shamsol Azman et al, 2023 ).…”