Bioactive Triterpenes of Protium heptaphyllum Gum Resin Extract Display Cholesterol-Lowering Potential
Abstract
:1. Introduction
2. Results and Discussion
2.1. HPLC-APCI-HRMS2(High Performance Liquid Chromatography coupled with Atmospheric Pressure Chemical Ionization and High Resolution Mass Spectrometry) and GC-FID/MS (Gas Chromatography coupled with Flame Ionization Detector and Mass Spectrometry) Analyses identified Tetra- and Pentacyclic Triterpenoic compounds as the main constituent of PHE
2.2. PHE Decreases Total Cholesterol in Hepatocytes
2.3. Triterpenoic Acids of PHE Modulate HMGCR Activity Assuming Similar Poses to LHE in the Active Site of the Enzyme
2.4. PHE Modulates the Expression of Cholesterol-Related Genes
3. Materials and Methods
3.1. Plant Material and Extract Preparation
3.2. Chemical Characterization Via HPLC-APCI-HRMS2
3.3. Chemical Characterization via GC-MS and GC-FID
3.4. Determination of Cholesterol Levels
3.5. Evaluation of HMGCR Activity
3.6. Molecular Docking Studies and Validation on HMGCR
3.6.1. Ligand and Protein Preparation
3.6.2. Molecular Docking
3.7. Gene Expression via qRT-PCR
3.8. Statistical Analysis
4. Conclusions
5. Patents
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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# | CAS ID | MW | Chemical Formula | Class | Name | Composition (%) |
---|---|---|---|---|---|---|
1 | 13466-78-9 | 136.23 | C10H16 | VOCs | Δ3-carene | 0.70 ± 0.08% |
2 | 99-87-6 | 134.22 | C10H14 | p-cymene | 0.90 ± 0.02% | |
3 | 638-95-9 | 556.9 | C39H56O2 | NATs | α-amyrin | 12.40 ± 1.39% |
4 | 559-70-6 | 426.7 | C30H50O | β-amyrin | 9.50 ± 1.17% | |
5 | 638-96-0 | 424.7 | C30H48O | α-amyron | 2.20 ± 0.08% | |
6 | 638-97-1 | 424.7 | C30H48O | β-amyron | 1.70 ± 0.61% | |
7 | 465-08-7 | 442.7 | C30H50O2 | Brein | 1.30 ± 0.08% | |
8 | 595-17-5 | 442.7 | C30H50O | Maniladiol | 0.90 ± 0.06% | |
9 | 508-02-1 | 456.7 | C30H48O3 | ATs | Oleanolic acid | 0.05 ± 0.01% |
10 | 77-52-1 | 456.7 | C30H48O3 | Ursolic acid | 0.06 ± 0.01% | |
11 | 28282-25-9 | 454.7 | C30H46O3 | Elemonic acid | 15.60 ± 0.06% | |
12 | 28282-27-1 | 456.7 | C30H48O3 | α-elemolic acid | 10.57 ± 0.76% | |
13 | 28282-54-4 | 456.7 | C30H48O3 | β-elemolic acid | 12.80 ± 1.38% |
# | Compound Name | Docking Score | Prime Energy | IFD Score |
---|---|---|---|---|
Lovastatin | −6.247 | −29124.9 | −1462.494 | |
Lovastatin Hydroxy Acid | −14.667 | −29097.0 | −1469.500 | |
1 | Δ3-carene | −3.220 | −29015.2 | −1453.979 |
2 | p-cymene | −4.009 | −29030.2 | −1455.521 |
3 | α-amyrin | −4.637 | −29073.5 | −1458.313 |
4 | β-amyrin | −4.405 | −29079.4 | −1458.376 |
5 | α-amyron | −5.196 | −29066.6 | −1458.528 |
6 | β-amyron | −4.245 | −29030.2 | −1455.753 |
7 | Brein | −5.307 | −29066.2 | −1458.666 |
8 | Maniladiol | −5.356 | −29151.0 | −1462.869 |
9 | Oleanolic acid | −9.835 | −29059.2 | −1462.795 |
10 | Ursolic acid | −8.008 | −29074.3 | −1461.721 |
11 | Elemonic acid | −6.786 | −29212.4 | −1467.408 |
12 | α-elemolic acid | −4.724 | −29220.5 | −1465.750 |
13 | β-elemolic acid | −6.828 | −29166.3 | −1465.142 |
Gene Acronym | Sequence (5′−3′) | Accession Number | |
---|---|---|---|
HMGCR | F | TGATTGACCTTTCCAGAGCAAG | NM_000859.2 |
R | CTAAAATTGCCATTCCACGAGC | ||
FXR | F | TCTCCTGGGTCGCCTGACT | NM_005123 |
R | ACTGCACGTCCCAGATTTCAC | ||
LDLR | F | AGTTGGCTGCGTTAATGTGA | NM_000527.4 |
R | TGATGGGTTCATCTGACCAGT | ||
IDOL | F | AAGTTCTTCGTGGAGCCTCA | NM_013262 |
R | ACTGAGTTCCACTGCCTGCT | ||
PCSK9 | F | GCTGAGCTGCTCCAGTTTCT | NM_174936.3 |
R | AATGGCGTAGACACCCTCAC | ||
PPARα | F | CTGGAAGCTTTGGCTTTACG | NM_005036.4 |
R | GTTGTGTGACATCCCGACAG | ||
βACT | F | CGGGAAATCGTGCGTGACAT | NM_001101.3 |
R | GGACTCCATGCCCAGGAAGG |
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Mannino, G.; Iovino, P.; Lauria, A.; Genova, T.; Asteggiano, A.; Notarbartolo, M.; Porcu, A.; Serio, G.; Chinigò, G.; Occhipinti, A.; et al. Bioactive Triterpenes of Protium heptaphyllum Gum Resin Extract Display Cholesterol-Lowering Potential. Int. J. Mol. Sci. 2021, 22, 2664. https://doi.org/10.3390/ijms22052664
Mannino G, Iovino P, Lauria A, Genova T, Asteggiano A, Notarbartolo M, Porcu A, Serio G, Chinigò G, Occhipinti A, et al. Bioactive Triterpenes of Protium heptaphyllum Gum Resin Extract Display Cholesterol-Lowering Potential. International Journal of Molecular Sciences. 2021; 22(5):2664. https://doi.org/10.3390/ijms22052664
Chicago/Turabian StyleMannino, Giuseppe, Piera Iovino, Antonino Lauria, Tullio Genova, Alberto Asteggiano, Monica Notarbartolo, Alessandra Porcu, Graziella Serio, Giorgia Chinigò, Andrea Occhipinti, and et al. 2021. "Bioactive Triterpenes of Protium heptaphyllum Gum Resin Extract Display Cholesterol-Lowering Potential" International Journal of Molecular Sciences 22, no. 5: 2664. https://doi.org/10.3390/ijms22052664
APA StyleMannino, G., Iovino, P., Lauria, A., Genova, T., Asteggiano, A., Notarbartolo, M., Porcu, A., Serio, G., Chinigò, G., Occhipinti, A., Capuzzo, A., Medana, C., Munaron, L., & Gentile, C. (2021). Bioactive Triterpenes of Protium heptaphyllum Gum Resin Extract Display Cholesterol-Lowering Potential. International Journal of Molecular Sciences, 22(5), 2664. https://doi.org/10.3390/ijms22052664