Phytochemical Analysis, Biological Activities, and Docking of Phenolics from Shoot Cultures of Hypericum perforatum L. Transformed by Agrobacterium rhizogenes
Abstract
:1. Introduction
- (1)
- phenolic profile (phenolic acids, flavan-3-ols, flavonols, anthocyanins, naphthodianthrones, acyl-phloroglucinols, and xanthones) in H. perforatum TSL and NTS extracts using HPLC/DAD/ESI-MSn methodology;
- (2)
- enzyme-inhibitory activity against monoamine oxidase-A (MAO-A), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase (TYR), α-amylase (α-AM), α-glucosidase (α-GL), pancreatic lipase (PL) and cholesterol esterase (CHE) by in vitro assays; and
- (3)
- potential interactions between representative phenolic compounds and target enzymes using molecular docking studies.
2. Results
2.1. HPLC/DAD/ESI-MSn Analysis of Phenolic Compounds in H. perforatum Transformed Shoots
2.2. In Vitro Biological Activity of H. perforatum Transformed Shoots
2.3. Molecular Modelling of Phenolic Compounds from H. perforatum Transformed Shoots
3. Discussion
3.1. Analysis of Phenolic Compounds in H. perforatum Transformed Shoots
3.2. Biological Activity of H. perforatum Transformed Shoots
4. Materials and Methods
4.1. Plant Material and Culture Conditions
4.2. Chromatographic Identification and Quantification of Phenolic Compounds
4.3. In Vitro Biological Activities
4.4. Molecular Modelling
4.5. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Peak | Phenolic Compounds | NTS | TSL B | TSL F | TSL H |
---|---|---|---|---|---|
Phenolic acids | |||||
F2 | Chlorogenic acid | 8.75 ± 1.01 c | 0.77 ± 0.06 a | 12.44 ± 1.63 d | 4.04 ± 0.89 b |
F3 | 3-p-Coumaroylquinic acid | 1.97 ± 0.43 b | 0.46 ± 0.27 a | 0.21 ± 0.16 a | 0.97 ± 0.52 ab |
F5 | 3-Feruloylquinic acid | 0.86 ± 0.07 b | n.d. | 0.29 ± 0.02 a | 1.23 ± 0.16 c |
Flavan-3-ols | |||||
F1 | (epi)catechin-(epi)gallocatechin dimer | n.d. | n.d. | 4.17 ± 0.53 | n.d. |
F4 | Procyanidin B2 | n.d. | 1.54 ± 0.17 a | 4.14 ± 0.38 b | 1.40 ± 0.11 a |
F6 | Procyanidin trimer | n.d. | n.d. | 3.71 ± 0.55 | n.d. |
F7 | (epi)catechin | 5.64 ± 0.41 b | 4.97 ± 0.25 ab | 6.05 ± 0.82 b | 4.62 ± 0.17 a |
Flavonol glycosides and aglycons | |||||
F9 | Quercetin 6-C-glucoside | 0.91 ± 0.05 a | n.d. | 0.95 ± 0.09 a | n.d. |
F11 | Kaempferol 6-C-glucoside | n.d. | 0.81 ± 0.04 b | 0.46 ± 0.07 a | 0.97 ± 0.11 b |
F12 | Hyperoside (quercetin 3-O-galactoside) | 2.22 ± 0.20 b | 1.47 ± 0.23 a | 2.41 ± 0.15 b | 1.66 ± 0.09 a |
F13 | Rutin (quercetin 3-O-rutinoside) | n.d. | 0.45 ± 0.02 | n.d. | n.d. |
F14 | Quercitrin (quercetin 3-O-rhamnoside) | 3.89 ± 0.52 ab | 4.15 ± 0.39 b | 3.06 ± 0.67 a | 3.00 ± 0.23 a |
F15 | Quercetin | 0.31 ± 0.02 a | 0.53 ± 0.07 b | 0.44 ± 0.05 b | 0.42 ± 0.05 b |
Anthocyanins | |||||
F8 | Cyanidin 3-O-glycoside | 0.08 ± 0.01 a | 0.13 ± 0.02 b | 0.13 ± 0.01 b | 0.11 ± 0.02 ab |
F10 | Cyanidin 3-O-rhamnoside | 1.42 ± 0.15 ab | 2.08 ± 0.13 c | 1.25 ± 0.10 a | 1.75 ± 0.21 bc |
Naphthodianthrones | |||||
F16 | Pseudohypericin | 0.66 ± 0.03 a | 1.91 ± 0.06 c | 0.76 ± 0.06 a | 1.18 ± 0.06 b |
F17 | Hypericin | 0.03 ± 0.00 b | 0.07 ± 0.00 d | 0.02 ± 0.00 a | 0.04 ± 0.00 c |
F18 | Protopseudohypericin | 0.09 ± 0.01 a | 0.48 ± 0.03 c | 0.35 ± 0.03 b | 0.58 ± 0.02 d |
Acyl-phloroglucinols | |||||
F19 | Hyperforin | 1.70 ± 0.13 b | 3.31 ± 0.27 c | 1.60 ± 0.10 b | 1.07 ± 0.08 a |
F20 | Adhyperforin | 0.40 ± 0.03 b | 0.35 ± 0.03 b | 0.19 ± 0.02 a | 0.38 ± 0.05 b |
Xanthones | |||||
X1 | Mangiferin | 11.26 ± 1.98 b | 4.47 ± 0.41 a | 12.97 ± 2.63 b | 4.81 ± 0.62 a |
X2 | Brasilixanthone B | n.d. | 1.85 ± 0.23 a | 1.72 ± 0.10 a | n.d. |
X3 | Trihydroxyxanthone-sulfonate | 7.88 ± 0.97 b | 5.97 ± 0.34 a | 8.37 ± 0.66 b | 6.04 ± 0.40 a |
X4 | Dimethylmangiferin | 1.08 ± 0.12 b | 1.52 ± 0.21 b | 0.30 ± 0.02 a | 0.99 ± 0.19 b |
X5 | Dihydroxy-metoxyxanthone-sulfonate | 4.73 ± 0.38 b | 4.49 ± 0.44 ab | 3.50 ± 0.32 a | 3.94 ± 0.58 ab |
X6 | Mangiferin C-prenyl isomer | 0.18 ± 0.01 a | n.d. | 0.16 ± 0.05 a | n.d. |
X7 | 1,3,6,7-Tetrahydroxyxanthone 2-prenyl xanthone | n.d. | 0.05 ± 0.00 a | 0.14 ± 0.02 b | n.d. |
X8 | 1,3,6,7-Tetrahydroxyxanthone 8-prenyl xanthone | n.d. | n.d. | 0.14 ± 0.01 | n.d. |
X9 | γ-Mangostin | 0.62 ± 0.04 b | 0.47 ± 0.06 a | 0.48 ± 0.04 a | 0.78 ± 0.10 b |
X10 | 5-O-Methyl-2-deprenylrheediaxanthone B | n.d. | n.d. | 0.21 ± 0.03 a | 0.15 ± 0.02 a |
X11 | Cadensin G | 6.83 ± 0.81 ab | 5.59 ± 0.77 a | 7.41 ± 0.46 b | 6.77 ± 0.61 ab |
MAO-A (IC50 µg·mL−1) | AChE (IC50 µg·mL−1) | BChE (IC25 µg·mL−1) | TYR (IC50 µg·mL−1) | α-AM (IC25 µg·mL−1) | α-GL (IC50 µg·mL−1) | PL (IC50 µg·mL−1) | CHE (IC50 µg·mL−1) | |
---|---|---|---|---|---|---|---|---|
NTS | 511.99 ± 51.70 bc | 1107.23 ± 78.76 d | 75.12 ± 10.56 b | 150.44 ± 10.12 d | 277.04 ± 30.15 d | 156.99 ± 9.78 b | 406.95 ± 49.64 c | 302.17 ± 1.91 c |
TSL B | 433.90 ± 30.03 b | 944.91 ± 59.11 c | 480.03 ± 14.34 c | 80.66 ± 2.25 b | 261.98 ± 12.96 d | 345.69 ± 37.48 c | 352.68 ± 26.34 c | 125.93 ± 12.70 b |
TSL F | 546.77 ± 47.03 c | 233.32 ± 25.82 b | 1257.49 ± 42.04 e | 147.59 ± 14.29 d | 214.43 ± 27.40 c | 879.90 ± 23.66 d | 230.39 ± 21.58 b | 572.04 ± 40.96 d |
TSL H | 566.16 ± 41.01 c | 217.90 ± 17.12 b | 850.49 ± 51.92 d | 119.16 ± 9.77 c | 169.91 ± 7.52 b | 298.86 ± 30.79 c | 254.80 ± 24.79 b | 102.50 ± 6.50 a |
DCP | 36.86 ± 0.70 a | n.t. | n.t. | n.t. | n.t. | n.t. | n.t. | n.t. |
Eserine | n.t. | 11.97 ± 0.64 a | 0.10 ± 0.02 a | n.t. | n.t. | n.t. | n.t. | n.t. |
Kojic acid | n.t. | n.t. | n.t. | 19.39 ± 1.77 a | n.t. | n.t. | n.t. | n.t. |
Acarbose | n.t. | n.t. | n.t. | n.t. | 6.77 ± 0.76 a | 15.43 ± 1.15 a | n.t. | n.t. |
Orlistat | n.t. | n.t. | n.t. | n.t. | n.t. | n.t. | 13.88 ± 0.77 a | n.t. |
Simvastatin | n.t. | n.t. | n.t. | n.t. | n.t. | n.t. | n.t. | 160.47 ± 28.29 b |
Ligands | Enzymes | Binding Energy (kcal·mol−1) | Inhibition Constant (Ki) |
---|---|---|---|
Chlorogenic acid | MAO-A | −7.31 | 4.4 µM |
AChE | −7.30 | 4.49 µM | |
BChE | −5.84 | 52.07 µM | |
TYR | −8.09 | 1.17 µM | |
α-AM | −4.30 | 703.86 µM | |
α-GL | −5.09 | 156.36 µM | |
PL | −6.14 | 31.74 µM | |
CHE | −5.02 | 208.55 µM | |
Epicatechin | MAO-A | −8.52 | 564.15 nM |
AChE | −8.19 | 995.35 nM | |
BChE | −8.45 | 635.22 nM | |
TYR | −4.37 | 622.42 µM | |
α-AM | −7.76 | 2.04 µM | |
α-GL | −7.44 | 3.51 µM | |
PL | −8.38 | 722.92 nM | |
CHE | −5.64 | 73.02 µM | |
Pseudohypericin | MAO-A | −6.50 | 17.15 µM |
AChE | −12.00 | 1.59 nM | |
BChE | −14.56 | 21.14 pM | |
TYR | −7.21 | 5.20 µM | |
α-AM | −11.58 | 3.27 nM | |
α-GL | −11.65 | 2.89 nM | |
PL | −12.70 | 489.00 pM | |
CHE | −10.51 | 19.91 nM | |
Hyperforin | MAO-A | −4.99 | 270.76 µM |
AChE | −8.49 | 600.06 nM | |
BChE | −11.06 | 7.75 nM | |
TYR | −6.37 | 21.33 µM | |
α-AM | −8.02 | 1.33 µM | |
α-GL | −10.30 | 28.32 nM | |
PL | −8.42 | 673.63 nM | |
CHE | −4.48 | 518.91 µM |
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Tusevski, O.; Todorovska, M.; Petreska Stanoeva, J.; Gadzovska Simic, S. Phytochemical Analysis, Biological Activities, and Docking of Phenolics from Shoot Cultures of Hypericum perforatum L. Transformed by Agrobacterium rhizogenes. Molecules 2024, 29, 3893. https://doi.org/10.3390/molecules29163893
Tusevski O, Todorovska M, Petreska Stanoeva J, Gadzovska Simic S. Phytochemical Analysis, Biological Activities, and Docking of Phenolics from Shoot Cultures of Hypericum perforatum L. Transformed by Agrobacterium rhizogenes. Molecules. 2024; 29(16):3893. https://doi.org/10.3390/molecules29163893
Chicago/Turabian StyleTusevski, Oliver, Marija Todorovska, Jasmina Petreska Stanoeva, and Sonja Gadzovska Simic. 2024. "Phytochemical Analysis, Biological Activities, and Docking of Phenolics from Shoot Cultures of Hypericum perforatum L. Transformed by Agrobacterium rhizogenes" Molecules 29, no. 16: 3893. https://doi.org/10.3390/molecules29163893