The Inhibitory Potential of Thai Mango Seed Kernel Extract against Methicillin-Resistant Staphylococcus Aureus
Abstract
:1. Introduction
2. Results and Discussion
2.1. Disc Diffusion Method
Bacterial strains | Mean diameter of inhibition zone (mm)a | |||||
---|---|---|---|---|---|---|
Control (solvents) | MSKE | Vancomycin 30 µg/disc | ||||
0.625 mg/disc | 1.25 mg/disc | 2.50 mg/disc | 5.00 mg/disc | |||
S. aureus ATCC 25923 | nz | 11.44 ± 0.59 | 14.81 ± 0.49 | 13.94 ± 1.34 | 17.06 ± 3.23 | 18.31 ± 0.52 |
Clinical MRSA strains | ||||||
M 01 | nz | 12.00 ± 0.14 | 14.08 ± 0.25 | 14.17 ± 0.23 | 18.25 ± 1.14 | 21.00 ± 0.33 |
M 02 | nz | 12.03 ± 0.19 | 14.11 ± 0.46 | 17.20 ± 2.31 | 17.92 ± 1.53 | 20.44 ± 2.50 |
M 03 | nz | 11.92 ± 0.68 | 15.58 ± 0.51 | 15.53 ± 0.90 | 20.50 ± 2.28 | 22.89 ± 2.01 |
M 04 | nz | 11.28 ± 0.38 | 14.08 ± 0.82 | 14.56 ± 0.55 | 18.19 ± 1.61 | 19.67 ± 0.33 |
M 05 | nz | 11.58 ± 0.52 | 13.69 ± 0.35 | 13.20 ± 0.52 | 16.03 ± 0.20 | 19.78 ± 0.19 |
M 06 | nz | 11.92 ± 0.82 | 14.89 ± 0.71 | 14.50 ± 1.65 | 18.78 ± 2.67 | 19.33 ± 0.67 |
M 07 | nz | 10.92 ± 0.46 | 14.28 ± 0.57 | 14.33 ± 0.71 | 18.53 ± 0.91 | 20.89 ± 0.84 |
M 08 | nz | 11.31 ± 0.51 | 14.36 ± 0.27 | 15.59 ± 0.52 | 19.34 ± 0.54 | 19.78 ± 0.69 |
M 09 | nz | 10.39 ± 0.46 | 13.08 ± 0.76 | 13.36 ± 0.51 | 17.97 ± 0.20 | 20.44 ± 1.95 |
M 10 | nz | 12.44 ± 0.51 | 15.72 ± 1.50 | 14.52 ± 0.35 | 18.36 ± 0.20 | 18.33 ± 0.58 |
M 11 | nz | 8.17 ± 0.29 | 10.06 ± 0.10 | 12.17 ± 0.76 | 13.56 ± 0.51 | 18.61 ± 0.54 |
M 12 | nz | 10.33 ± 0.44 | 12.11 ± 0.10 | 14.11 ± 0.25 | 15.72 ± 0.10 | 19.11 ± 1.07 |
M 13 | nz | 9.11 ± 0.10 | 10.72 ± 0.59 | 12.72 ± 0.69 | 14.72 ± 0.86 | 18.33 ± 1.04 |
M 14 | nz | 8.56 ± 0.35 | 10.56 ± 0.35 | 13.00 ± 0.17 | 14.61 ± 0.54 | 21.89 ± 1.95 |
M 15 | nz | 10.44 ± 0.67 | 12.39 ± 0.54 | 14.22 ± 1.51 | 16.83 ± 1.09 | 20.61 ± 1.69 |
M 16 | nz | 9.56 ± 0.25 | 11.00 ± 0.29 | 13.67 ± 0.33 | 15.39 ± 0.38 | 19.67 ± 0.73 |
M 17 | nz | 10.28 ± 0.19 | 11.61 ± 0.42 | 13.61 ± 0.69 | 15.39 ± 0.54 | 19.28 ± 0.54 |
M 18 | nz | 9.44 ± 1.08 | 10.83 ± 0.60 | 12.61 ± 0.92 | 15.00 ± 0.76 | 20.44 ± 1.80 |
M 19 | nz | 9.94 ± 1.55 | 11.28 ± 1.44 | 12.89 ± 1.55 | 15.06 ± 1.40 | 18.72 ± 0.92 |
Mean MRSA (n = 19) b | nz | 10.61 ± 1.25* | 12.87 ±1.82* | 14.00 ±1.21* | 16.85 ±1.94* | 19.96 ± 1.20* |
2.2. The Minimum Inhibitory Concentrations (MICs) and Minimum Bactericidal Concentrations (MBCs)
Bacterial strains | Susceptibility of Bacteriaa | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
MSKE (mg/mL) | PGG (mg/mL) | MG (mg/mL) | GA (mg/mL) | Vancomycin (µg/mL) | Penicillin G (µg/mL) | |||||||
MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | |
S. aureus ATCC 25923 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.13 ± 0.00 | 0.50 ± 0.00 | 0.38 ± 0.00 | 1.00 ± 0.00 | 0.19 ± 0.00 | 0.75 ± 0.00 | 0.78 ± 0.00 | 3.13 ± 0.00 | 41.67 ± 18.04 | 41.67 ± 18.04 |
Clinical MRSA strains | ||||||||||||
M 01 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.17 ± 0.07 | 1.00 ± 0.00 | 1.25 ± 0.43 | 1.50 ± 0.00 | 0.25 ± 0.11 | 0.75 ± 0.00 | 1.56 ± 0.00 | 6.25 ± 0.00 | 2,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 02 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.17 ± 0.07 | 1.00 ± 0.00 | 1.00 ± 0.43 | 1.25 ± 0.43 | 0.38 ± 0.00 | 0.63 ± 0.22 | 1.56 ± 0.00 | 6.25 ± 0.00 | 2,000.00 ± 0.00 | 5,333.33 ± 2,309.40 |
M 03 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.13 ± 0.00 | 1.00 ± 0.00 | 1.25 ± 0.43 | 1.25 ± 0.43 | 0.38 ± 0.00 | 0.63 ± 0.22 | 1.56 ± 0.00 | 6.25 ± 0.00 | 2,000.00 ± 0.00 | 4,000.00 ± 0.00 |
M 04 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.13 ± 0.00 | 1.00 ± 0.00 | 1.25 ± 0.43 | 1.25 ± 0.43 | 0.25 ± 0.11 | 0.50 ± 0.22 | 1.56 ± 0.00 | 6.25 ± 0.00 | 1,333.33 ± 577.35 | 2,666.67 ± 1,154.70 |
M 05 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.13 ± 0.00 | 1.00 ± 0.00 | 1.25 ± 0.43 | 1.50 ± 0.00 | 0.38 ± 0.00 | 1.00 ± 0.43 | 1.56 ± 0.00 | 6.25 ± 0.00 | 2,000.00 ± 0.00 | 5,333.33 ± 2,309.40 |
M 06 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.17 ± 0.07 | 1.00 ± 0.00 | 1.25 ± 0.43 | 1.25 ± 0.43 | 0.25 ± 0.11 | 0.38 ± 0.00 | 1.56 ± 0.00 | 12.50 ± 0.00 | 1,666.67 ± 577.35 | 4,000.00 ± 0.00 |
M 07 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.17 ± 0.07 | 1.00 ± 0.00 | 1.25 ± 0.43 | 1.75 ± 1.15 | 0.63 ± 0.22 | 0.75 ± 0.00 | 1.56 ± 0.00 | 6.25 ± 0.00 | 2,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 08 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.17 ± 0.07 | >1.00 ± 0.00 | 1.25 ± 0.43 | 1.25 ± 0.43 | 0.38 ± 0.00 | 0.38 ± 0.00 | 1.56 ± 0.00 | 6.25 ± 0.00 | 1,666.67 ± 577.35 | 4,000.00 ± 0.00 |
M 09 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.17 ± 0.07 | 1.00 ± 0.00 | 1.25 ± 0.43 | 1.25 ± 0.43 | 0.38 ± 0.00 | 0.38 ± 0.00 | 1.56 ± 0.00 | 12.50 ± 0.00 | 1,666.67 ± 577.35 | 4,000.00 ± 0.00 |
M 10 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.17 ± 0.07 | >1.00 ± 0.00 | 1.25 ± 0.43 | 1.50 ± 0.00 | 0.63 ± 0.22 | 0.75 ± 0.00 | 1.56 ± 0.00 | 6.25 ± 0.00 | 1,666.67 ± 577.35 | 8,000.00 ± 0.00 |
M 11 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.17 ± 0.07 | 1.00 ± 0.00 | 1.50 ± 0.00 | 1.50 ± 0.00 | >3.00 ± 0.00 | >3.00 ± 0.00 | 1.56 ± 0.00 | 12.50 ± 0.00 | 2,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 12 | 0.47 ± 0.00 | 3.75 ± 0.00 | 0.13 ± 0.00 | >1.00 ± 0.00 | 2.50 ± 0.87 | 2.50 ± 0.87 | >3.00 ± 0.00 | >3.00 ± 0.00 | 1.56 ± 0.00 | 12.50 ± 0.00 | 4,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 13 | 0.47 ± 0.00 | 3.75 ± 0.00 | 0.17 ± 0.07 | 1.00 ± 0.00 | 0.75 ± 0.00 | 1.00 ± 0.43 | 0.25 ± 0.11 | 0.75 ± 0.00 | 6.25 ± 0.00 | 12.50 ± 0.00 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 14 | 0.47 ± 0.00 | 0.94 ± 0.00 | 0.13 ± 0.00 | 1.00 ± 0.00 | 1.25 ± 0.43 | 1.25 ± 0.43 | 0.63 ± 0.22 | 0.75 ± 0.00 | 3.13 ± 0.00 | 12.50 ± 0.00 | 4,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 15 | 0.47 ± 0.00 | 0.94 ± 0.00 | 0.13 ± 0.00 | 1.00 ± 0.00 | 1.50 ± 0.00 | 1.50 ± 0.00 | >3.00 ± 0.00 | >3.00 ± 0.00 | 3.13 ± 0.00 | 12.50 ± 0.00 | 125.00 ± 0.00 | 125.00 ± 0.00 |
M 16 | 0.47 ± 0.00 | 0.94 ± 0.00 | 0.25 ± 0.00 | 1.00 ± 0.00 | 1.50 ± 0.00 | 1.50 ± 0.00 | >3.00 ± 0.00 | >3.00 ± 0.00 | 3.13 ± 0.00 | 12.50 ± 0.00 | 4,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 17 | 0.47 ± 0.00 | 0.94 ± 0.00 | 0.13 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.43 | 1.00 ± 0.43 | 0.31 ± 0.11 | 0.75 ± 0.00 | 3.13 ± 0.00 | 12.50 ± 0.00 | 125.00 ± 0.00 | 125.00 ± 0.00 |
M 18 | 0.47 ± 0.00 | 0.94 ± 0.00 | 0.17 ± 0.07 | 1.00 ± 0.00 | 1.50 ± 0.00 | 1.50 ± 0.00 | 0.19 ± 0.00 | 0.38 ± 0.00 | 3.13 ± 0.00 | 12.50 ± 0.00 | 2,000.00± 0.00 | 8,000.00 ± 0.00 |
M 19 | 0.47 ± 0.00 | 1.88 ± 0.00 | 0.17 ± 0.07 | 1.00 ± 0.00 | 1.50 ± 0.00 | 1.50 ± 0.00 | >3.00 ± 0.00 | >3.00 ± 0.00 | 1.56 ± 0.00 | 3.13 ± 0.00 | 2,000.00± 0.00 | 8,000.00 ± 0.00 |
Mean MRSA (n = 19) b | 0.47 ± 0.00 | 1.83 ± 0.79 | 0.16 ± 0.03 | >1.00 ± 0.00 | 1.33 ± 0.34 | 1.42 ± 0.32 | >1.07 ± 1.19 | >1.25 ± 1.09 | 2.22 ± 1.20 | 9.38 ± 3.45 | 2,328.95 ± 1,729.87 | 5,767.54 ± 2,748.78 |
2.3. Time–Kill Curves
2.4. Electron Microscopy
2.5. The Enhancing Effects of MSKE and Its Phenolic Principles on the Antibacterial Activity of Penicillin G
Bacterial strains | MIC of Penicillin G (µg/mL)a | ||||||||
---|---|---|---|---|---|---|---|---|---|
Penicillin G alone | +MSKE 0.25MIC | +MSKE 0.5MIC | +PGG 0.25MIC | +PGG 0.5MIC | +MG 0.25MIC | +MG 0.5MIC | +GA 0.25MIC | +GA 0.5MIC | |
S. aureus ATCC 25923 | 41.67 ± 18.04 | 3.91 ± 0.00 | 1.95 ± 0.00 | 7.81 ± 0.00 | 7.81 ± 0.00 | 31.25 ± 0.00 | 15.63 ± 0.00 | 15.63 ± 0.00 | 7.81 ± 0.00 |
Clinical MRSA strains | |||||||||
M 01 | 2,000.00 ± 0.00 | 500.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 62.50 ± 0.00 | 1.95 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
M 02 | 2,000.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 125.00 ± 0.00 | 1.95 ± 0.00 | 250.00 ± 0.00 | 125.00 ± 0.00 |
M 03 | 2,000.00 ± 0.00 | 500.00 ± 0.00 | 250.00 ± 0.00 | 1,000.00 ± 0.00 | 500.00 ± 0.00 | 125.00 ± 0.00 | 1.95 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
M 04 | 1,333.33 ± 577.35 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 125.00 ± 0.00 | 1.95 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
M 05 | 2,000.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 125.00 ± 0.00 | 1.95 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
M 06 | 1,666.67 ± 577.35 | 250.00 ± 0.00 | 250.00 ± 0.00 | 500.00 ± 0.00 | 250.00 ± 0.00 | 62.50 ± 0.00 | 1.95 ± 0.00 | 3.91 ± 0.00 | 3.91 ± 0.00 |
M 07 | 2,000.00 ± 0.00 | 500.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 125.00 ± 0.00 | 1.95 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
M 08 | 1,666.67 ± 577.35 | 250.00 ± 0.00 | 250.00 ± 0.00 | 1,000.00 ± 0.00 | 500.00 ± 0.00 | 250.00 ± 0.00 | 125.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
M 09 | 1,666.67 ± 577.35 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 3.91 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
M 10 | 1,666.67 ± 577.35 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 125.00 ± 0.00 | 125.00 ± 0.00 | 3.91 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
M 11 | 2,000.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 3.91 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
M 12 | 4,000.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 1,000.00 ± 0.00 | 1,000.00 ± 0.00 | 2,000.00 ± 0.00 | 3.91 ± 0.00 | 1,000.00 ± 0.00 | 1,000.00 ± 0.00 |
M 13 | 8,000.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 3.91 ± 0.00 | 125.00 ± 0.00 | 125.00 ± 0.00 |
M 14 | 4,000.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 250.00 ± 0.00 | 3.91 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
M 15 | 125.00 ± 0.00 | 62.50 ± 0.00 | 62.50 ± 0.00 | 7.80 ± 0.00 | 7.80 ± 0.00 | 3.91 ± 0.00 | 0.06 ± 0.00 | 3.91 ± 0.00 | 3.91 ± 0.00 |
M 16 | 4,000.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 3.91 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
M 17 | 125.00 ± 0.00 | 62.50 ± 0.00 | 62.50 ± 0.00 | 31.25 ± 0.00 | 31.25 ± 0.00 | 3.91 ± 0.00 | 0.06 ± 0.00 | 3.91 ± 0.00 | 3.91 ± 0.00 |
M 18 | 2,000.00 ± 0.00 | 500.00 ± 0.00 | 250.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 62.50 ± 0.00 | 3.91 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
M 19 | 2,000.00 ± 0.00 | 500.00 ± 0.00 | 500.00 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 | 62.50 ± 0.00 | 3.91 ± 0.00 | 250.00 ± 0.00 | 250.00 ± 0.00 |
Mean MRSA (n = 19) b | 2,328.95 ± 1,729.87 | 361.84 ± 159.45 | 309.21 ±145.05 | 409.95 ± 300.04 | 324.42 ± 222.60 | 250.41 ± 439.73 | 9.16 ± 28.08 | 244.04 ± 205.36 | 237.46 ± 207.16 |
Bacterial strains | MBC of Penicillin G (µg/mL) a | ||
---|---|---|---|
Penicillin G alone | with MSKE 0.5 MIC | with MSKE 1 MIC | |
S. aureus ATCC 25923 | 41.67 ± 18.04 | 31.25 ± 0.00 | 31.25 ± 0.00 |
Clinical MRSA strains | |||
M 01 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 02 | 5,333.33 ± 2,309.40 | 4,000.00 ± 0.00 | 4,000.00 ± 0.00 |
M 03 | 4,000.00 ± 0.00 | 4,000.00 ± 0.00 | 4,000.00 ± 0.00 |
M 04 | 2,666.67 ± 1,154.70 | 4,000.00 ± 0.00 | 4,000.00 ± 0.00 |
M 05 | 5,333.33 ± 2,309.40 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 06 | 4,000.00 ± 0.00 | 4,000.00 ± 0.00 | 4,000.00 ± 0.00 |
M 07 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 08 | 4,000.00 ± 0.00 | 4,000.00 ± 0.00 | 4,000.00 ± 0.00 |
M 09 | 4,000.00 ± 0.00 | 4,000.00 ± 0.00 | 4,000.00 ± 0.00 |
M 10 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 11 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 12 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 13 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 14 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 15 | 125.00 ± 0.00 | 125.00 ± 0.00 | 125.00 ± 0.00 |
M 16 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 17 | 125.00 ± 0.00 | 125.00 ± 0.00 | 125.00 ± 0.00 |
M 18 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 |
M 19 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 | 8,000.00 ± 0.00 |
Mean MRSA (n = 19) b | 5,767.54 ± 2,748.78 | 5,907.89 ± 2,757.52 | 5,907.89 ± 2,757.52 |
3. Experimental
3.1. Materials
3.1.1. Test Materials
3.1.2. Plant Material and Preparation of Plant Extract
3.1.3. Standardisation
3.1.4. Bacterial Strains Tested
3.2. Antimicrobial Susceptibility Test
3.2.1. Disc Diffusion Method
3.2.2. Determination of the MICs and MBCs
3.2.3. Time−Kill Assay
3.3. Electron Microscopy
3.3.1. SEM
3.3.2. TEM
3.4. Statistical Analysis
4. Conclusions
Acknowledgments
Conflict of Interest
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Jiamboonsri, P.; Pithayanukul, P.; Bavovada, R.; Chomnawang, M.T. The Inhibitory Potential of Thai Mango Seed Kernel Extract against Methicillin-Resistant Staphylococcus Aureus. Molecules 2011, 16, 6255-6270. https://doi.org/10.3390/molecules16086255
Jiamboonsri P, Pithayanukul P, Bavovada R, Chomnawang MT. The Inhibitory Potential of Thai Mango Seed Kernel Extract against Methicillin-Resistant Staphylococcus Aureus. Molecules. 2011; 16(8):6255-6270. https://doi.org/10.3390/molecules16086255
Chicago/Turabian StyleJiamboonsri, Pimsumon, Pimolpan Pithayanukul, Rapepol Bavovada, and Mullika T. Chomnawang. 2011. "The Inhibitory Potential of Thai Mango Seed Kernel Extract against Methicillin-Resistant Staphylococcus Aureus" Molecules 16, no. 8: 6255-6270. https://doi.org/10.3390/molecules16086255