Recent Advances in Synthesis, Bioactivity, and Pharmacokinetics of Pterostilbene, an Important Analog of Resveratrol
Abstract
:1. Introduction
2. Resources and Synthesis
2.1. Resources
2.2. Chemical Synthesis and Biosynthesis of Pterostilbene
3. Pharmacokinetics
3.1. Absorption
3.2. Distribution
3.3. Metabolism
3.4. Excretion
4. Bioactivities of Pterostilbene
4.1. Anti-Tumor Activity
4.2. Anti-Inflammation Activity
4.3. Neuroprotective Activity
4.3.1. Cerebral Ischemia
4.3.2. Alzheimer’s Disease
4.3.3. Others
4.4. Antioxidation Activity
4.5. Lipid-Lowering Activity
4.5.1. Serum Lipids
4.5.2. Liver Steatosis
4.5.3. Obesity
4.6. Hypoglycemic Activity
4.7. Others
4.7.1. Antifungal Activity
4.7.2. Antiviral Activity
4.7.3. Antipsychotic Activity
5. Conclusions and Prospects
Author Contributions
Funding
Conflicts of Interest
References
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Subject | Mode of Administration | Dose (mg/kg) | AUC (mg h/L) | V (L/kg) | CL (mL/min/kg) | T1/2 (min) | Reference |
---|---|---|---|---|---|---|---|
C57 BL/6 mice | iv. | 10 | 26.7 ± 8.2 | Vc 0.674 ± 0.12 | (0.014 ± 0.003) × 103 | 34.5 ± 1.0 | [16] |
C57 BL/6 mice | ig. | 14 | 4.43 ± 2.0 | Vc 4.9 ± 1.9 | (0.027 ± 0.008) × 103 | 102± 19.2 | [16] |
C57 BL/6 mice | ig. | 28 | 11.9 ± 2.1 | Vc 3.76 ± 0.85 | (0.012 ± 0.008) × 103 | 87.8 ± 29.2 | [16] |
C57 BL/6 mice | ig. | 56 | 39.4 ± 9.7 | Vc 1.57 ± 0.27 | (0.030 ± 0.005) × 103 | 56.9 ± 13.9 | [16] |
SD rat | iv. | 2.5 | (35.6 ± 5.1)/60 | Vc 2.85 ± 0.50 | 68.2 ± 9.8 | 93.9 ± 22.3 | [35] |
SD rat | iv. | 5 | (135,650 ± 8944)/(60 × 103) | Vc (1267 ± 364)/103 | 37.0 ± 2.5 | 96.6 ± 23.7 | [43] |
SD rat | iv. | 10 | (168.7 ± 28.6)60 | Vc 3.03 ± 0.88 | 59.1 ± 8.8 | 155.1 ± 64.1 | [35] |
SD rat | iv. | 11.2 | 4009/103 | Vss 5.30 | 2.7 × 103/60 | 2.9 × 60 | [17] |
SD rat | iv. | 20 | 17.5 ± 6.6 | Vd 2.41 ± 1.13 | (0.960 ± 0.025) × 103/60 | (1.73 ± 0.87) × 60 | [39] |
SD rat | iv. | 25 | (689.2 ± 124.1)/60 | Vc 2.19 ± 0.17 | 36.4 ± 7.8 | 150.8 ± 15.9 | [35] |
Wistar rat | iv. | 22.5 | (38.8 ± 5.3) × 256.3/103 | Vss 6.1 ± 1.0 | (2.3 ± 0.3) × 103/60 | (1.8 ± 0.3) × 60 | [36] |
Signaling Pathway | Model | Dose | Reference |
---|---|---|---|
EGFR, Akt/mTOR, Stat3, ERK1/2, and NFκB pathways | urethane-caused lung tumor | 250 mg/kg | [48] |
microRNA 448 circuit | MDA-MB-231 cells were cocultured with M2 TAM and were subcutaneously injected into the left flank of NOD/SCID mice | 5 mg/kg | [49] |
JAK/STAT3 signaling pathway | Breast cancer cell lines (MDA-231 and ZR-751) | 75 μM | [50] |
Src/Fak signaling pathway | MDA-MB-231-bearing NOD/SCID mice | 10 mg/kg | [51] |
Rac1/WAVE/Arp2/3 pathway | MDA-MB-231 cells | 10 μM | [52] |
β-catenin/p65 downstream signaling pathway | F344 rats were given two AOM injections subcutaneously | 0.004% in the diet for 45 weeks | [53] |
ATM/CHK/p53 pathway | non-small cell lung cancer cell (A549) | 21 μM | [54] |
GRP78 signaling pathway | human glioblastoma cell lines GBM8401 and U87MG | 2.99, 1.42 μM | [46] |
p53/SOD2/ROS pathway | HepG2 cells | 100 μM | [55] |
miR-663b/BCL2L14 signaling pathway | HTB-111 and Ishikawa cells | 71.64 nM, 74.34 µM | [56] |
JAK2/STAT3 signaling pathway | human osteosarcoma cell line, SOSP-9607 | 1.81 µM | [57] |
AKT/mTOR/p70S6K and ERK1/2 pathways | T24 human bladder cancer cell | 66.58 ± 1.84 µM | [58] |
Fas/FasL pathway | human AGS gastric carcinoma cells (CCRC 60102) | 50.7 μM | [47] |
ERS signaling pathway | Human EC109 and TE1 esophageal cancer cells | 150 μM | [59] |
RAGE/PI3K/Akt signaling pathway | MIA PaCa-2 and MIA PaCa-2GEMR cells (GEM-resistant cells) | 41.8, 42.0 µM | [60] |
signal transducer and activator of transcription 3 signaling pathway | HeLa, CaSki, and SiHa cervical cancer adherent cells | 32.67, 14.83, 34.17 µM | [61] |
Model | Dose | Reference |
---|---|---|
Human keratinocytes, mouse epidermal cells | 3.75, 7.5, 15 μM | [80] |
human retinal endothelial cells | 1.0 mM | [81] |
Streptozotocin–nicotinamide-induced type 2 diabetes mellitus in Wistar rats | 40 mg/kg for 6 weeks | [8] |
Model | Dose | Reference |
---|---|---|
H4IIEC3 cells | 100 µM | [11] |
Obese Otsuka Long–Evans Tokushima fatty rats | 0.5% diet for 4 weeks | [82] |
3T3-L1 mature adipocytes | 5 µM | [83] |
Mice fed an obesogenic high-fat diet | 352 µmol/kg/d for 30 weeks | [83] |
Genetic obesity Zucker (fa/fa) rats | 15, 30 mg/kg body weight/day for 6 weeks | [84,85] |
Wistar rats fed an obesogenic diet | 15, 30 mg/kg body weight/day for 6 weeks | [86,87] |
3T3-F442A preadipocytes | 1–10 μM | [88] |
3T3-L1 preadipocytes | 5–40 μM | [89] |
Genetic obesity Zucker (fa/fa) rats | 15 mg/kg body weight/day for 6 weeks | [90] |
Model | Dose | Reference |
---|---|---|
Streptozotocin-nicotinamide-induced diabetic male albino Wistar rats | 10, 20, 40 mg/kg for 2, 4, 6 weeks | [91] |
Islet β cells of INS-1E rats induced by streptozotocin | 4, 8 μM | [12] |
Moderate diabetic mice with glycosuria and hyperglycemia | 5 mg/kg for 5 weeks | [11] |
Insulin resistance associated Wistar rats with obesity feeding | 15 mg/kg body weight/d for 6 weeks | [93] |
Diabetes was induced in rats by streptozotocin and a high-sugar and high-fat diet | 20, 40 and 80 mg/kg/d for 8 weeks | [94] |
Model | Dose | Reference |
---|---|---|
Conidia of Botrytis cinerea | 60 μg/mL | [2] |
Fusobacterium nucleatum | 0.02 mg/mL | [95] |
HIV-1 infection in resting CD4 T cells | 5 μM | [96] |
Transformed fibroblast cell line | 10 μM | [97] |
Elevated plus maze test mice | 2 mg/kg | [98] |
Chronic unexpected stressed model rats | 2.5 mg/L | [99] |
In Vivo or In Vitro | Model | Comparison | Mechanism | Reference |
---|---|---|---|---|
In vitro | Multidrug resistant HL60-R (human myeloid cell line expressing P-glycoprotein) | AC50 of pterostilbene is 85 ± 11, resveratrol has almost no effect on inducing apoptosis | Caspase-independent pathway | [15] |
In vitro | HT-29 human adenocarcinoma cell line | Pterostilbene (IC50, 22.4 μmol/L), resveratrol (IC50, 43.8 μmol/L) | P38 mitogen-activated protein kinase cascade | [14] |
In vivo | Mouse susceptibility No. 8 (SAMP8) AD model | Pterostilbene was a more effective cognitive and cellular stress regulator than resveratrol | The increasing of the expression of peroxisome proliferator-activated receptor α | [10] |
In vivo | Wistar rats fed an obesogenic diet | Pterostilbene is more effective than resveratrol at a dose of 15 mg/kg/d | The decrease of lipogenesis in adipose tissue and the increase of fatty acid oxidation in liver | [88] |
In vivo | Wistar rats fed an obesogenic diet | 15 mg/kg body weight/d was not as effective as pterostilbene in reducing serum glucose levels | The increase of liver glucokinase activity and skeletal muscle glucose uptake | [93] |
In vitro | Fusobacterium nucleatum | The minimum inhibitory concentration was more than 60 times lower than that of resveratrol | Inducing the leakage of cell contents, which resulted in the loss of bacterial cell vitality | [95] |
Sample Availability: Samples of the compounds pterostilbene and resveratrol are available from the authors. |
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Liu, Y.; You, Y.; Lu, J.; Chen, X.; Yang, Z. Recent Advances in Synthesis, Bioactivity, and Pharmacokinetics of Pterostilbene, an Important Analog of Resveratrol. Molecules 2020, 25, 5166. https://doi.org/10.3390/molecules25215166
Liu Y, You Y, Lu J, Chen X, Yang Z. Recent Advances in Synthesis, Bioactivity, and Pharmacokinetics of Pterostilbene, an Important Analog of Resveratrol. Molecules. 2020; 25(21):5166. https://doi.org/10.3390/molecules25215166
Chicago/Turabian StyleLiu, Yeju, Yuyang You, Juan Lu, Xi Chen, and Zhihong Yang. 2020. "Recent Advances in Synthesis, Bioactivity, and Pharmacokinetics of Pterostilbene, an Important Analog of Resveratrol" Molecules 25, no. 21: 5166. https://doi.org/10.3390/molecules25215166
APA StyleLiu, Y., You, Y., Lu, J., Chen, X., & Yang, Z. (2020). Recent Advances in Synthesis, Bioactivity, and Pharmacokinetics of Pterostilbene, an Important Analog of Resveratrol. Molecules, 25(21), 5166. https://doi.org/10.3390/molecules25215166