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
:1. Introduction
2. Materials and Methods
2.1. Materials
Source of Seeds
2.2. Methods
2.2.1. Seed Preparation, Extraction, and Chromatographic Analysis
2.2.2. Screening of Active Compounds, Drug Therapeutics, and Disease Targets
2.2.3. Protein–Protein Interaction (PPI) Network Construction
2.2.4. Kyoto Encyclopaedia of Genes and Genomes (KEGG) Pathways Enrichment Analyses
2.2.5. Molecular Docking
3. Results
3.1. Compounds Identification and ADME Properties Screening
3.2. Screening of Active Compounds and Their Targets
3.3. Screening of T2D Disease Targets, Drugs, and Disease Candidates
3.4. Protein–Protein Interaction Network
3.5. KEGG Enrichment Analysis
3.6. Molecular Docking
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
References
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S/N | Compound Names | Lipinski’s Rule Remarks | No of Violations |
---|---|---|---|
1 | Capric acid | Yes | None |
2 | Caproic acid | Yes | None |
3 | Caprylic acid | Yes | None |
4 | Lauric acid | Yes | None |
5 | Myristic acid | Yes | None |
6 | Palmitic acid | Yes | None |
7 | Pentadecyclic acid | Yes | None |
8 | Stearic acid | Yes | None |
9 | Oleic acid | Yes | None |
10 | Linoleic acid | Yes | None |
11 | Arachidic acid | Yes | None |
12 | Behenic acid | Yes | None |
13 | Tricosylic acid | Yes | None |
14 | Lignoceric acid | Yes | None |
15 | Phylloquinone | Yes | None |
Term ID | Pathways | No of Genes | False Discovery Rate | Genes |
---|---|---|---|---|
hsa03320 | PPAR signaling pathway | 5 | 2.01 × 10−6 | FABP4, PPARG, PPARD, CPT2, PPARA |
hsa04080 | Neuroactive ligand-receptor interaction | 5 | 1.20 × 10−3 | CNR1, LPAR1, LPAR3, GPR35, TRPV1 |
hsa05200 | Pathways in cancer | 5 | 7.00 × 10−3 | PPARG, PPARD, RARB, LPAR1, LPAR3 |
S/N | Compounds/Standards | Docking Scores (kcal/mol) | ||||
---|---|---|---|---|---|---|
PPARA | FABP4 | PPARD | PPARG | CPT2 | ||
1 | Linoleic acid | −6.3 | −6.3 | NA | NA | NA |
2 | Lignoceric acid | −6.7 | −6.0 | NA | −6.1 | −5.7 |
3 | Behenic acid | −6.5 | −5.9 | NA | NA | −6.1 |
4 | Phylloquinone | −9.2 | NA | NA | NA | NA |
5 | Tricosylic acid | −6.6 | −6.0 | −7.1 | −5.7 | −5.7 |
6 | Arachidic acid | NA | −5.9 | −6.1 | −5.8 | −6.2 |
7 | Pentadecyclic acid | NA | NA | −6.3 | NA | NA |
8 | Stearic acid | NA | NA | −6.3 | −5.8 | −6.3 |
9 | Oleic acid | NA | NA | −6.4 | NA | NA |
10 | Palmitic acid | NA | NA | NA | −5.8 | NA |
11 | Rosiglitazone | −8.6 | −8.3 | −8.7 | −8.2 | −9.4 |
12 | Metformin | −5.2 | −4.5 | −5.2 | −4.9 | −5.3 |
Complex | Number of Interactions | Number of H-Bonds and Interaction Residues | Number of van der Waal Forces and Interaction Residues | Other Important Interactions and Residues |
---|---|---|---|---|
PPARA–phylloquinone | 25 | - | 16 (Gln277, Met330, Met320, Thr279, Gly335, Val332, Tyr334, Leu460, Tyr464, His440, Tyr314, Ser280, Thr283, Asn219, Phe318, Lys358) | 9 (Cys276, Met355, Ile354, Ile317, Leu321, Val324, Met220, Leu331, Phe273) |
PPARA–lignoceric acid | 22 | 2 (His440, Tyr464) | 14 (Tyr314, Lys358, Met355, Cys276, Gln277, Ser280, Thr283, Met320, Asn219, Thr279, Tyr334, Gly335, Val332, Leu331) | 6 (Phe318, Ile217, Leu321, Met220, Met330, Val324) |
PPARA–behenic acid | 21 | - | 12 (Phe218, Met320, Val324, Thr283, Thr279, Tyr314, Phe318, Ile354, Gln277, Asn219, Met220, Ser280) | 9 (Leu321, Ile317, His440, Cys226, Phe273, Leu458, Leu460, Val444, Tyr464) |
PPARA–tricosylic acid | 21 | 3 (Gln277, Ser280, Tyr464) | 9 (Val444, Phe318, Thr279, Val332, Tyr334, Leu331, Thr283, Tyr314, Leu460) | 9 (Ile354, Phe273, Lys276, His440, Leu321, Ile317, Met320, Val324, Met220) |
PPARA–linoleic acid | 14 | 1 (Cys276) | 9 (Val332, Leu331, Asn219, Glu286, Phe218, Thr283, Thr279, Ile317, Ser280) | 4 (Met220, Met320, Val324, Leu321) |
PPARA–rosiglitazone | 20 | 1 (Ser280) | 14 (Asn219, Phe218, Met220, Ser323, Val324, Asn221, Met320, Thr279, Phe318, Lys358, Ile354, Gln277, Thr283, Met355) | 5 (Ile317, Leu321, His440, Cys276, Phe273) |
PPARA–metformin | 13 | 2 (Tyr214, Thr283) | 9 (Lys 222, Thr279, Val324, Ser323, Asn221, Met220, Met220, Asn219, Phe218) | 2 (Glu286, Asp372) |
FABP4–linoleic acid | 22 | 1 (Arg126) | 12 (Gln95, Thr74, Arg78, Val25, Asp76, Lys58, Ser53, Ser55, Cys117, Val115, Tyr128, Arg106) | 9 (Tyr19, Phe16, Met20, Ala75, Ala33, Ala36, Pro38, Phe57, Ile104) |
FABP4–lignoceric acid | 8 | 1 (Thr29) | 4 (Met35, Phe27, Phe57, Lys58) | 3 (Lys31, Val32, Ala28) |
FABP4–aradichic acid | 10 | 2 (Ala75, Asp76) | 4 (Asp77, Thr29, Lys58, Phe27) | 4 (Val32, Phe57, Ala28, Lys31) |
FABP4–behenic acid | 22 | 1 (Arg106) | 11 (Arg78, Asp76, Ser55, Lys58, Ser53, Arg126, Thr60, Ile104, Met40, Val115, Tyr128) | 10 (Val25, Val23, Tyr19, Met20, Phe57, Ala33, Ala36, Ala75, Phe16, Pro38) |
FABP4–tricosylic acid | 24 | 2 (Ala75, Thr24) | 11 (Glu72, Thr60, Asp76, Arg78, Arg126, Ser53, Lys58, Ser55, Val25, Tyr19, Arg106) | 11 (Met20, Ala36, Pro38, Phe51, Ala33, The16, Tyr128, Cys117, Ile104, Met40, Val115) |
FABP4–rosiglitazone | 22 | 2 (Arg106, Ser53) | 14 (Val23, Arg78, Tyr19, Val115, Tyr128, Ser55, Val25, Met20, Asp76, Gln95, Ala75, Ala33, Phe57, Thr60) | 6 (Phe16, Cys117, Ile104, Arg126, Pro38, Ala36) |
FABP4–metformin | 10 | 1 (Tyr128) | 7 (Met40, Pro38, Ala75, Ala36, Phe57, Phe16, Ala33) | 2 (Arg126, Ser53) |
PPARD–tricosylic acid | 25 | 1 (His287) | 9 (Phe316, Trp228, Leu317, Thr252, Phe291, Phe246, Gln250, Leu433, Met417) | 15 (Leu219, Ile213, Val312, Arg218, Val245, Leu323, Val305, Leu294, Cys249, Ile322, Ile328, Tyr437, Thr253, Lys331, His413) |
PPARD–oleic acid | 19 | 1 (Thr252) | 4 (Trp228, Thr253, Ile290, Leu317) | 13 (Phe316, Arg248, Val305, Leu294, Leu303, Cys249, Ile328, Lys331, Phe291, Val312, Val245, Leu219, Ile213) |
PPARD–stearic acid | 20 | 6 (Thr253, Gln250, Phe246, Phe291, His244, Phe316), 1 (His413) | 1 (His413) | 13 (Leu219, Arg248, Val245, Val312, Leu303, Cys249, Lys331, Ile328, Leu317, Leu294, Ile213, Val305, Trp228) |
PPARD–arachidic acid | 23 | 2 (His413, Thr253) | 8 (Trp228, Phe316, Ile290, Tyr437, His287, Met417, Leu433, Gln250) | 13 (Lys331, Phe291, Leu294, Ile328, Val305, Val312, Ile213, Cys249, Arg248, Leu219, Val245, Leu317, Leu303) |
PPARD—pentadecylic acid | 19 | - | 7 (His287, His413, Ile290, Thr253, Phe291, Phe316, Trp228) | 12 (Ile328, Val305, Val245, Leu219, Leu294, Leu303, Arg248, Lys331, Leu317, Val312, Ile213, Cys249) |
PPARD—rosiglitazone | 19 | 3 (Val245, His244, Ile327) | 11 (Leu219, Arg248, Ile328, Lys331, Met417, Phe246, Thr253, Phe291, Val305, Ile213, Trp228) | 5 (Val312, Leu317, Leu303, Cys249, His413) |
PPARD–metformin | 9 | 2 (Met293, Thr256) | 5 (Tyr186, Asn191, Met192, Ile297, Ser296) | 2 (Glu259, Phe190) |
PPARG–lignoceric acid | 24 | 1 (Gln286) | 15 (Ser289, Val339, Leu340, Ile341, Glu295, Phe226, Pro227, Phe287, Phe363, His449, Tyr327, Met364, Ser342, Lys367, Leu453) | 8 (Cys285, Arg288, Leu333, Ala292, Met329, Ile326, Leu228, Leu330) |
PPARG–palmitic acid | 20 | 1 (Gln286) | 12 (Leu228, Glu295, Ile296, Ser289, Tyr322, His323, Tyr473, His449, Leu453, Lys367, Cys285, Met364) | 7 (Pro227, Phe226, Met329, Arg288, Ile326, Ala292, Leu330) |
PPARG–stearic acid | 18 | 2 (Gln286, His449) | 6 (Glu295, Lys367, Phe363, Ser280, Tyr322, Ile296) | 10 (Phe226, Met329, Ala297, Ile326, Arg288, Glu330, Pro227, Leu228, Cys285, Met364) |
PPARG–arachidic acid | 16 | 1 (Glu343) | 9 (Leu228, Leu340, Ser342, Val339, Met364, Leu333, Ser289, Glu295, Tyr327) | 6 (Cys285, Ile341, Leu330, Ile326, Ala292, Met329) |
PPARG–tricosylic acid | 18 | 1 (Glu295) | 7 (Glu343, Ser342, Pro227, Phe226, Leu340, Ser289, Ile325) | 10 (Leu228, Leu333, Arg288, Leu330, Ala292, Met329, Ile326, Ile296, Cys285, Ile341) |
PPARG–rosiglitazone | 17 | 6 (Leu228, Arg288, Pro227, Phe226, Ser332, Cys285) | 6 (Glu295, Ile341, Thr229, Met329, Leu333, Ser289, Ile341) | 5 (Ile326, Ala292, Leu330, Val339, Met364) |
PPARG–metformin | 12 | 2 (Leu228, Ile326) | 9 (Pro227, Phe226, Arg288, Met329, Leu333, Ala292, Ser332, Ile296, Leu330) | 1 (Glu295) |
CPT2–stearic acid | 16 | 3 (Thr499, Ser488, Tyr120) | 7 (Asp376, Trp116, Arg554, Ser588, Asn585, Met119, Asn130), | 6 (Tyr486, Val605, His372, Phe131, Phe602, Pro133) |
CPT2–tricosylic acid | 22 | 3 (Ser488, Tyr486, Asp376) | 9 (Arg554, Trp116, Thr499, Met119, Gly377, Ser590, Asn585, Ser588, Asn130) | 9 (Val605, Phe131, Phe602, Met135, His372, Tyr120, Phe370, Pro133, Leu592) |
CPT2–lignoceric acid | 15 | 2 (Val175, Glu174) | 3 (Ser490, Val378, Arg382) | 10 (Phe176, Leu212, Ala547, Tyr210, Ala493, Phe494, Met548, Pro50, Trp201, Tyr205) |
CPT2–arachidic acid | 16 | 2 (Ser498, Tyr486) | 9 (Trp116, Thr499, Arg554, Met119, Asn130, Ser590, Phe370, Ty120, Ser588) | 5 (Val605, Phe131, Phe602, His372, Pro133) |
CPT2–behenic acid | 17 | 3 (Tyr486, Ser488, Asp376), | 8 (Asn585, Ser588, Ser590, Trp116, Asn130, Tyr120, Thr499, Arg554) | 6 (Val605, Phe131, Met119, Phe602, His372, Pro133) |
CPT2–rosiglitazone | 21 | 1 (Ser590) | 15 (Val597, Ala615, Leu599, His617, Ser598, Trp620, Gly622, Asn624, Cys623, Thr591, Gly600, Tyr614, Phe370, His372, Ser588) | 4 (Ala613, Phe602, Pro133, Met135, Leu592) |
CPT2–metformin | 12 | 3 (Phe131, Ala603, Leu129) | 8 (Asn132, Pro133, Asn130, His372, Leu343, Pro604, Val605, Ser588) | 1 (Phe602) |
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Rampadarath, A.; Balogun, F.O.; Sabiu, S. 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. Endocrines 2023, 4, 327-349. https://doi.org/10.3390/endocrines4020026
Rampadarath A, Balogun FO, Sabiu S. 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. Endocrines. 2023; 4(2):327-349. https://doi.org/10.3390/endocrines4020026
Chicago/Turabian StyleRampadarath, Athika, Fatai Oladunni Balogun, and Saheed Sabiu. 2023. "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" Endocrines 4, no. 2: 327-349. https://doi.org/10.3390/endocrines4020026