Anti-Melanogenic Activity of Ethanolic Extract from Garcinia atroviridis Fruits Using In Vitro Experiments, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Plant Materials
2.3. Plant Preparation
2.4. Determination of Total Phenolic Content (TPC) and Total Flavonoid Content (TFC)
2.5. DPPH Radical Scavenging Activity
2.6. ABTS Radical Scavenging Activity
2.7. Cell Culture and Cell Viability Assay
2.8. Measurement of Intracellular Tyrosinase Activity and Melanin Content
2.9. Quantitative Real-Time PCR (qRT-PCR)
2.10. Western Blot Analysis
2.11. Copper-Chelating Assay (CCA)
2.12. Liquid Chromatography–Mass Spectrometry (LC-MS) Analysis
2.13. Chemoinformatics, Drug Likeness and Pharmacokinetic Prediction
2.14. Network Pharmacology Analysis
2.14.1. Target Protein Prediction
2.14.2. Disease Potential Targets
2.14.3. GO and KEGG Pathway Enrichment Analysis
2.14.4. Construction of Protein–Protein Interaction Network
2.15. Molecular Docking Verification
2.16. Molecular Dynamics Simulation
2.17. Statistical Analysis
3. Results and Discussion
3.1. Extraction Yield, Total Phenolic and Total Flavonoid Contents of Ethanolic Extract of G. atroviridis Fruits
3.2. Free Radical Scavenging Activities of Ethanolic Extract of G. atroviridis Fruits
3.3. Effects of Ethanolic Extract of G. atroviridis Fruits on Cell Viability, Intracellular Tyrosinase Activity, and Melanin Content
3.4. Effects of Ethanolic Extract of G. atroviridis Fruits on Melanogenesis-Related Gene Expression
3.5. Effects of Ethanolic Extract of G. atroviridis Fruits on Protein Expression of Melanogenesis Related Proteins
3.6. Effects of Ethanolic Extract of G. atroviridis Fruits on Copper-Chelating Activity
3.7. Liquid Chromatography–Mass Spectrometry (LC-MS) Analysis
3.8. Chemoinformatics, Drug Likeness, and Pharmacokinetic Properties of Compounds from Ethanolic Extract of G. atroviridis Fruits
3.9. Network Pharmacology Analysis
3.9.1. Target Identification and Analysis
3.9.2. GO and KEGG Enrichment Analysis
3.9.3. Network Analysis of Protein–Protein Interactions (PPI) and Identification of Key Targets
3.10. Confirmation of Hub Targets through Molecular Docking
3.11. MD Simulation
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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No. | RT (min) | Mass | Chemical Formula | Error (ppm) | Identification |
---|---|---|---|---|---|
Positive Mode of Analysis | |||||
1 | 1.707 | 598.3291 | C38H46O6 | −0.6 | Gambogin |
2 | 4.552 | 168.0422 | C8H8O4 | −0.49 | 2,6-Dimethoxy-p-benzoquinone |
3 | 7.745 | 484.3538 | C31H48O4 | −2.99 | Garcihombronane J |
4 | 14.752 | 196.0524 | C13H8O2 | −0.19 | Xanthone |
5 | 16.833 | 372.2166 | C19H32O7 | 4.86 | Blumenol-C-O-β-D-glucoside |
6 | 19.329 | 408.1577 | C24H24O6 | 0.98 | Garcimangosone B |
7 | 19.818 | 442.1618 | C24H26O6 | −2.21 | Mangostenone C |
8 | 22.106 | 300.1365 | C18H20O4 | 1.10 | (S)-3-hydroxygarcibenzopyran |
Negative Mode of Analysis | |||||
1 | 2.319 | 192.0267 | C6H8O7 | −1.32 | Citric acid |
2 | 5.051 | 190.0109 | C6H6O7 | −2.18 | Garcinia lactone |
3 | 5.733 | 352.0951 | C20H16O6 | 1.06 | Subelliptenone C |
4 | 12.335 | 132.0422 | C5H8O4 | −0.71 | 2-Acetoxypropanoic acid |
5 | 15.068 | 164.0472 | C9H8O3 | −0.96 | p-Coumaric acid |
6 | 15.524 | 432.1071 | C21H20O10 | 3.43 | Kaempferol-3-O-a-L-rhamnoside |
7 | 17.401 | 182.0575 | C9H10O4 | −1.99 | Methyl orsellinate |
8 | 19.109 | 398.1745 | C23H26O6 | 3.95 | Nigrolineaxanthone L |
9 | 19.166 | 420.2287 | C27H32O4 | −3.29 | Clusiachromene D |
10 | 19.848 | 362.1717 | C20H26O6 | −3.29 | Parvifoliol B |
11 | 20.133 | 384.1209 | C21H20O7 | 0.12 | Dulxanthone F |
12 | 20.759 | 250.1941 | C16H26O2 | 3.32 | Scortechterpene B |
13 | 21.329 | 636.3679 | C38H52O8 | 2.65 | Garcimultiflorone F |
14 | 21.955 | 576.4400 | C35H60O6 | 1.69 | β-Sitosterol-3-O-β-D-glucoside |
15 | 22.012 | 380.1634 | C23H24O5 | 2.78 | Vismiaphenone E |
16 | 22.012 | 426.1691 | C24H26O7 | 2.90 | Parvixanthones H |
17 | 22.126 | 428.1845 | C24H28O7 | 2.22 | Garcinone D |
18 | 22.581 | 502.3085 | C33H42O4 | 0.33 | Kolanone |
19 | 22.582 | 400.3348 | C27H44O2 | 1.63 | Garcinielliptone |
20 | 23.150 | 410.1747 | C24H26O6 | 4.40 | Mangostin |
21 | 23.150 | 364.1685 | C23H24O4 | 2.92 | Clusiachromene C |
22 | 24.857 | 586.3672 | C38H50O5 | 2.28 | Guttiferone J |
23 | 25.429 | 394.1797 | C24H26O5 | 4.31 | Cudraxanthone G |
24 | 26.453 | 574.4245 | C35H58O6 | 1.97 | Stigmasta-5,22-dien-3-O-β-glucopyranoside |
25 | 26.909 | 570.3724 | C38H50O4 | 2.55 | 13,14-Didehydroxyisogarcinol |
Identification | Pubchem CID | Physicochemical Properties | Drug-Likeness | ||||
---|---|---|---|---|---|---|---|
MW (g/mol) | HBA | HBD | TPSA (Å2) | logP | |||
Gambogin | 15298998 | 598.77 | 6 | 1 | 82.06 | 7.04 | No |
2,6-dimethoxy-p-benzoquinone | 68262 | 168.15 | 4 | 0 | 52.6 | 0.22 | Yes |
Garcihombronane J | 11670274 | 484.71 | 4 | 1 | 63.6 | 5.69 | Yes |
Xanthone | 7020 | 196.2 | 2 | 0 | 30.21 | 2.84 | Yes |
Blumenol-C-O-β-D-glucoside | 14135394 | 372.45 | 7 | 4 | 116.45 | 0.91 | Yes |
Garcimangosone B | 11143989 | 408.44 | 6 | 1 | 78.13 | 4.33 | Yes |
Mangostenone C | 11546716 | 442.46 | 8 | 4 | 129.59 | 3.13 | Yes |
(S)-3-hydroxygarcibenzopyran | - | 300.35 | 4 | 2 | 58.92 | 2.94 | Yes |
Citric acid | 311 | 192.12 | 7 | 4 | 132.13 | −1.51 | Yes |
Garcinia lactone | 9991606 | 190.11 | 7 | 3 | 121.13 | −1.34 | Yes |
Subelliptenone C | 101681084 | 352.34 | 6 | 3 | 104.04 | 3.51 | Yes |
2-acetoxypropanoic acid | 79041 | 132.11 | 4 | 1 | 63.6 | 0.06 | Yes |
p-Coumaric acid | 637542 | 164.16 | 3 | 2 | 57.53 | 1.26 | Yes |
Kaempferol-3-O-a-L-rhamnoside | 5835713 | 432.38 | 10 | 6 | 170.05 | 0.6 | Yes |
Methyl orsellinate | 76658 | 182.17 | 4 | 2 | 66.76 | 1.4 | Yes |
Nigrolineaxanthone L | 11749894 | 398.45 | 6 | 3 | 100.13 | 3.8 | Yes |
Clusiachromene D | 21602027 | 420.54 | 4 | 3 | 69.92 | 5.73 | Yes |
Parvifoliol B | 163184032 | 306.35 | 5 | 4 | 97.99 | 3.39 | Yes |
Dulxanthone F | 10500218 | 384.38 | 7 | 1 | 87.36 | 3.34 | Yes |
Scortechterpene B | 101746891 | 236.35 | 2 | 0 | 26.3 | 2.96 | Yes |
Garcimultiflorone F | 46919309 | 636.81 | 8 | 5 | 152.36 | 5.88 | No |
β-sitosterol-3-O-β-D-glucoside | 12309057 | 576.85 | 6 | 4 | 99.38 | 5.51 | No |
Vismiaphenone E | 474315 | 380.43 | 5 | 3 | 86.99 | 4.02 | Yes |
Parvixanthones H | 11080433 | 426.46 | 7 | 4 | 120.36 | 3.86 | Yes |
Garcinone D | 5495926 | 428.47 | 7 | 4 | 120.36 | 3.91 | Yes |
Kolanone | 6439598 | 502.68 | 4 | 2 | 74.6 | 7.01 | No |
Garcinielliptone | - | 400.64 | 2 | 1 | 37.3 | 5.7 | Yes |
Mangostin | 5281650 | 410.46 | 6 | 3 | 100.13 | 4.64 | Yes |
Clusiachromene C | 16070714 | 364.43 | 4 | 2 | 66.76 | 4.43 | Yes |
Guttiferone J | 102031302 | 586.8 | 5 | 2 | 91.67 | 7.8 | No |
Cudraxanthone G | 42645953 | 394.46 | 5 | 2 | 79.9 | 5.02 | Yes |
Stigmasta-5,22-dien-3-O-β-glucopyranoside | 6602508 | 574.83 | 6 | 4 | 99.38 | 5.1 | No |
13,14-didehydroxyisogarcinol | 25243255 | 570.8 | 4 | 0 | 60.44 | 7.74 | No |
Identification | Pharmacokinetic Properties | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
GI Absorption | BBB Permeant | P-gp Substrate | CYP1A2 Inhibitor | CYP2C19 Inhibitor | CYP2C9 Inhibitor | CYP2D6 Inhibitor | CYP3A4 Inhibitor | Log Kp (cm/s) | AMES Toxicity | hERG I Inhibitor | hERG II Inhibitor | Hepato-Toxicity | Skin Sensitisation | |
Gambogin | Low | No | Yes | No | No | No | No | Yes | −3.82 | No | No | No | No | No |
2,6-Dimethoxy-p-benzoquinone | High | No | No | No | No | No | No | No | −7.37 | No | No | No | No | Yes |
Garcihombronane J | High | No | No | No | No | No | No | Yes | −5.17 | No | No | No | No | No |
Xanthone | High | Yes | No | Yes | No | No | No | No | −5.09 | Yes | No | No | No | Yes |
Blumenol-C-O-β-D-glucoside | High | No | Yes | No | No | No | No | No | −8.36 | No | No | No | No | No |
Garcimangosone B | High | No | Yes | No | Yes | Yes | No | No | −5.22 | No | No | Yes | No | No |
Mangostenone C | High | No | No | No | No | Yes | No | No | −6.05 | Yes | No | Yes | No | No |
(S)-3-hydroxygarcibenzopyran | High | Yes | Yes | Yes | No | No | Yes | Yes | −5.88 | Yes | No | Yes | No | No |
Citric acid | Low | No | No | No | No | No | No | No | −8.69 | No | No | No | No | No |
Garcinia lactone | Low | No | No | No | No | No | No | No | −8.33 | No | No | No | No | No |
Subelliptenone C | High | No | No | Yes | No | Yes | No | No | −5.04 | No | No | Yes | No | No |
2-Acetoxypropanoic acid | High | No | No | No | No | No | No | No | −7.03 | No | No | No | No | No |
p-Coumaric acid | High | Yes | No | No | No | No | No | No | −6.26 | No | No | No | No | No |
Kaempferol-3-O-a-L-rhamnoside | Low | No | No | No | No | No | No | No | −8.07 | No | No | Yes | No | No |
Methyl orsellinate | High | Yes | No | No | No | No | No | No | −6.01 | Yes | No | No | No | No |
Nigrolineaxanthone L | High | No | No | No | No | Yes | No | No | −5.66 | Yes | No | Yes | Yes | No |
Clusiachromene D | High | No | No | No | Yes | No | No | No | −3.71 | No | No | Yes | No | No |
Parvifoliol B | High | No | No | No | No | Yes | No | No | −4.43 | No | No | No | No | No |
Dulxanthone F | High | No | No | No | Yes | Yes | No | Yes | −5.8 | Yes | No | Yes | No | No |
Scortechterpene B | High | Yes | No | No | No | No | No | No | −5.64 | No | No | No | No | Yes |
Garcimultiflorone F | Low | No | Yes | No | No | No | No | Yes | −4.5 | No | No | No | Yes | No |
β-Sitosterol-3-O-β-D-glucoside | Low | No | No | No | No | No | No | No | −4.32 | No | No | No | No | No |
Vismiaphenone E | High | No | No | Yes | No | Yes | No | Yes | −4.64 | No | No | Yes | No | No |
Parvixanthones H | High | No | No | No | No | Yes | No | Yes | −5.24 | Yes | No | Yes | No | No |
Garcinone D | High | No | No | No | No | No | No | No | −5.43 | No | No | Yes | No | No |
Kolanone | Low | No | Yes | No | Yes | No | No | Yes | −2.81 | No | No | No | No | No |
Garcinielliptone | High | No | No | No | No | No | No | No | −3.72 | No | No | No | No | No |
Mangostin | High | No | No | No | No | Yes | No | No | −4.35 | Yes | No | Yes | No | No |
Clusiachromene C | High | No | No | Yes | Yes | Yes | No | Yes | −4.28 | No | No | Yes | No | No |
Guttiferone J | Low | No | Yes | No | No | No | No | Yes | −2.26 | No | No | No | No | No |
Cudraxanthone G | High | No | No | No | Yes | Yes | No | No | −4 | Yes | No | Yes | No | No |
Stigmasta-5,22-dien-3-O-β-glucopyranoside | High | No | Yes | No | No | No | No | No | −4.86 | No | No | No | No | No |
13,14-Didehydroxyisogarcinol | Low | No | Yes | No | No | No | No | No | −2.96 | No | No | No | No | No |
Ligands | Docking Scores (kcal/mol) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
TNF | MAPK3 | PTGS2 | EGFR | SRC | PPARG | CTNNB1 | ERBB2 | MDM2 | MAPK1 | MIFT | TYR | TYRP1 | MC1R | |
2,6-Dimethoxy-p-benzoquinone | −5.0 | −5.5 | −5.4 | −5.4 | −4.8 | −5.1 | −4.8 | −5.2 | −3.8 | −5.0 | −4.5 | −5.0 | −3.8 | −4.4 |
Garcihombronane J | −7.8 | −7.1 | −7.1 | −7.6 | −7.0 | −6.6 | −5.8 | −7.3 | −7.3 | −5.7 | −6.1 | −7.3 | −4.6 | −5.6 |
Blumenol-C-O-β-D-glucoside | −7.6 | −8.4 | −7.1 | −7.4 | −7.7 | −6.6 | −6.7 | −6.5 | −7.0 | −7.3 | −6.5 | −7.1 | −4.9 | −6.1 |
Garcimangosone B | −8.5 | −9.8 | −9.3 | −10.3 | −9.8 | −8.6 | −7.8 | −7.7 | −7.9 | −8.4 | −7.8 | −7.6 | −6.5 | −7.7 |
Citric acid | −4.7 | −4.8 | −5.0 | −5.7 | −5.0 | −5.1 | −5.1 | −5.5 | −3.8 | −4.7 | −4.5 | −5.6 | −4.4 | −4.5 |
Garcinia lactone | −5.4 | −5.7 | −5.8 | −5.7 | −5.8 | −4.9 | −6.0 | −5.8 | −4.5 | −5.2 | −5.1 | −5.7 | −5.8 | −4.5 |
Subelliptenone C | −8.6 | −9.5 | −10.9 | −9.1 | −8.9 | −9.1 | −7.5 | −8.7 | −7.2 | −8.6 | −7.4 | −7.4 | −7.0 | −7.4 |
2-Acetoxypropanoic acid | −4.2 | −4.7 | −4.8 | −5.1 | −4.6 | −4.5 | −4.4 | −5.3 | −3.0 | −4.4 | −4.0 | −5.0 | −4.2 | −4.0 |
p-Coumaric acid | −5.7 | −6.6 | −5.2 | −5.9 | −5.7 | −5.5 | −5.0 | −5.8 | −4.9 | −5.5 | −5.1 | −5.3 | −6.6 | −5.0 |
Kaempferol-3-O-a-L-rhamnoside | −7.5 | −10.4 | −7.7 | −8.3 | −7.8 | −6.4 | −6.7 | −7.5 | −6.4 | −9.0 | −7.4 | −6.5 | −5.6 | −7.2 |
Clusiachromene D | −8.6 | −7.5 | −7.6 | −8.0 | −6.8 | −6.4 | −7.2 | −7.6 | −7.9 | −5.9 | −6.6 | −6.5 | −5.8 | −8.1 |
Parvifoliol B | −6.6 | −8.2 | −7.3 | −7.0 | −6.7 | −6.1 | −5.5 | −8.5 | −6.6 | −7.2 | −4.7 | −7.0 | −5.4 | −5.5 |
Scortechterpene B | −6.7 | −6.9 | −5.6 | −7.4 | −7.1 | −5.6 | −5.4 | −6.5 | −6.4 | −6.2 | −4.8 | −5.8 | −4.5 | −5.5 |
Vismiaphenone E | −8.1 | −8.7 | −7.1 | −9.3 | −7.9 | −7.5 | −7.1 | −8.0 | −7.9 | −7.3 | −7.2 | −8.2 | −6.6 | −7.6 |
Garcinone D | −7.4 | −8.0 | −8.5 | −8.2 | −7.6 | −5.9 | −6.0 | −6.6 | −6.5 | −7.4 | −6.1 | −6.2 | −5.6 | −5.7 |
Garcinielliptone | −8.8 | −8.4 | −9.2 | −9.3 | −8.5 | −7.6 | −6.9 | −8.8 | −9.3 | −7.1 | −8.1 | −7.7 | −6.3 | −8.4 |
Clusiachromene C | −8.7 | −9.1 | −8.3 | −9.7 | −8.0 | −8.2 | −6.1 | −7.5 | −7.5 | −8.3 | −5.9 | −6.5 | −5.8 | −8.5 |
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Tedasen, A.; Chiabchalard, A.; Tencomnao, T.; Yamasaki, K.; Majima, H.J.; Phongphithakchai, A.; Chatatikun, M. Anti-Melanogenic Activity of Ethanolic Extract from Garcinia atroviridis Fruits Using In Vitro Experiments, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation. Antioxidants 2024, 13, 713. https://doi.org/10.3390/antiox13060713
Tedasen A, Chiabchalard A, Tencomnao T, Yamasaki K, Majima HJ, Phongphithakchai A, Chatatikun M. Anti-Melanogenic Activity of Ethanolic Extract from Garcinia atroviridis Fruits Using In Vitro Experiments, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation. Antioxidants. 2024; 13(6):713. https://doi.org/10.3390/antiox13060713
Chicago/Turabian StyleTedasen, Aman, Anchalee Chiabchalard, Tewin Tencomnao, Kenshi Yamasaki, Hideyuki J. Majima, Atthaphong Phongphithakchai, and Moragot Chatatikun. 2024. "Anti-Melanogenic Activity of Ethanolic Extract from Garcinia atroviridis Fruits Using In Vitro Experiments, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation" Antioxidants 13, no. 6: 713. https://doi.org/10.3390/antiox13060713
APA StyleTedasen, A., Chiabchalard, A., Tencomnao, T., Yamasaki, K., Majima, H. J., Phongphithakchai, A., & Chatatikun, M. (2024). Anti-Melanogenic Activity of Ethanolic Extract from Garcinia atroviridis Fruits Using In Vitro Experiments, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation. Antioxidants, 13(6), 713. https://doi.org/10.3390/antiox13060713