| Description: |
Pterostilbene acts as a peroxisome proliferator-activated receptor alpha (PPARalpha) agonist, it has been implicated in anticarcinogenesis, antioxidant, modulation of neurological disease, anti-inflammation, attenuation of vascular disease, and amelioration of diabetes. Pterostilbene downregulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NFkappaB by interfering with the activation of PI3K/Akt/IKK and MAPK.
Pterostilbene may protect HUVECs against oxLDL-induced apoptosis by downregulating LOX-1-mediated activation through a pathway involving oxidative stress, p53, mitochondria, cytochrome c and caspase protease.
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| In vitro: |
| J Agric Food Chem. 2008 Aug 27;56(16):7502-9. | | Pterostilbene suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages.[Pubmed: 18656926 ] | Pterostilbene, an active constituent of blueberries, is known to possess anti-inflammatory activity and also to induce apoptosis in various types of cancer cells.
METHODS AND RESULTS:
Here, we investigated the inhibitory effects of Pterostilbene on the induction of NO synthase (NOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with lipopolysaccharide (LPS). Western blotting and real-time polymerase chain reaction (PCR) analyses demonstrated that Pterostilbene significantly blocked the protein and mRNA expression of iNOS and COX-2 in LPS-induced macrophages. Treatment with Pterostilbene resulted in the reduction of LPS-induced nuclear translocation of the nuclear factor-kappaB (NFkappaB) subunit and the dependent transcriptional activity of NFkappaB by blocking phosphorylation of inhibitor kappaB (IkappaB)alpha and p65 and subsequent degradation of IkappaB alpha. Transient transfection experiments using NFkappaB reporter constructs indicated that Pterostilbene inhibits the transcriptional activity of NFkappaB in LPS-stimulated mouse macrophages. We found that Pterostilbene also inhibited LPS-induced activation of PI3K/Akt, extracellular signal-regulated kinase 1/2 and p38 MAPK.
CONCLUSIONS:
Taken together, these results show that Pterostilbene down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NFkappaB by interfering with the activation of PI3K/Akt/IKK and MAPK. These results have an important implication for using Pterostilbene toward the development of an effective anti-inflammatory agent. | | Plant Foods Hum Nutr. 2015 May 26. | | Pterostilbene, an Active Constituent of Blueberries, Stimulates Nitric Oxide Production via Activation of Endothelial Nitric Oxide Synthase in Human Umbilical Vein Endothelial Cells.[Pubmed: 26008990] | Endothelial dysfunction, a key process in development of cardiovascular diseases, is largely due to reduced nitric oxide (NO) derived from endothelial NO synthase (eNOS). Resveratrol has been reported to stimulate NO production via estrogen receptor α (ERα) activation in endothelial cells.
METHODS AND RESULTS:
Here, we investigated whether two natural methylated analogs of resveratrol, Pterostilbene (Pts) and trans-3,5,4'-trimethoxystilbene (TMS), similarly to resveratrol, could influence endothelial NO release in human umbilical vein endothelial cells (HUVECs). In HUVECs exposed to Pts or TMS, NO production and phosphorylation of eNOS, protein kinase B (Akt), and ERα were measured by using a fluorimetric NO assay kit and Western blot analysis, respectively. Dimethylated Pts, but not trimethylated TMS, stimulated dose-dependent NO production via eNOS phosphorylation. Pts also stimulated dose-dependent phosphorylation of Akt, but not of ERα. NO production and eNOS phosphorylation in response to Pts were significantly abolished by the phosphoinositide 3-kinase (PI3K)/Akt inhibitor LY294002, but not by the ERα antagonist ICI182780.
CONCLUSIONS:
Our results suggest that Pts, but not TMS, is capable of inducing eNOS phosphorylation and the subsequent NO release, presumably, by activating PI3K/Akt pathway. The potential efficacy of Pts, an active constituent of blueberries, may aid in the prevention of cardiovascular diseases characterized by endothelial dysfunction. | | J BUON . Sep-Oct 2018;23(5):1384-1389. | | Pterostilbene (3',5'-dimethoxy-resveratrol) exerts potent antitumor effects in HeLa human cervical cancer cells via disruption of mitochondrial membrane potential, apoptosis induction and targeting m-TOR/PI3K/Akt signalling pathway[Pubmed: 30570862] | | Abstract
Purpose: To examine the molecular mechanism of action behind the anticancer effects of Pterostilbene in HeLa human cervical cancer cells.
Methods: MTS assay was used to study the Pterostilbene cytotoxic effects, while inverted phase contrast and fluorescence microscopy was used to study the effects of the drug on the cell apoptosis and changes in cell morphology. Flow cytometry was used to study changes in mitochondrial membrane potential (MMP), while immunoblotting assay was used to demonstrate its effects on m-TOR/PI3K/Akt protein signalling pathway.
Results: Pterostilbene induced potent, dose-dependent and time-dependent cytotoxic effects in HeLa cancer cells exhibiting IC50 of 101.2 μM and 65.9 μM at 24 and 48 hrs time intervals, respectively. As compared to the untreated control cells which revealed normal cell morphology, Pterostilbene-treated cells exhibited significant cellular shrinkage which increased with increasing doses of the drug. Untreated control cells showed complete green fluorescence corresponding to absence of apoptosis. However, Pterostilbene-treated cells with 25, 100 and 200 μM showed increasing emission of red/orange fluorescence corresponding to apoptotic induction. Pterostilbene-treated cells showed evident signs of DNA ladder formation and the effect increased with increasing concentrations of the drug. The percentage of cells with depolarized mitochondria (loss of MMP) increased from 2.3% in the control group to 24.5, 43.2 and 65.8% in cells treated with 0, 25, 100 and 200 μM concentration of Pterostilbene, respectively.
Conclusion: Pterostilbene exerts potent anticancer effects in HeLa human cervical cancer cells via disruption of MMP, apoptosis induction and targeting m-TOR/PI3K/Akt signalling pathway. |
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| In vivo: |
| Food Funct. 2015 Jun 10;6(6):1968-76. | | Pterostilbene improves glycaemic control in rats fed an obesogenic diet: involvement of skeletal muscle and liver.[Pubmed: 25998070] | This study aims to determine whether Pterostilbene improves glycaemic control in rats showing insulin resistance induced by an obesogenic diet.
METHODS AND RESULTS:
Rats were divided into 3 groups: the control group and two groups treated with either 15 mg kg(-1) d(-1) (PT15) or 30 mg kg(-1) d(-1) of Pterostilbene (PT30). HOMA-IR was decreased in both Pterostilbene-treated groups, but this reduction was greater in the PT15 group (-45% and -22% respectively vs. the control group). The improvement of glycaemic control was not due to a delipidating effect of Pterostilbene on skeletal muscle. In contrast, GLUT4 protein expression was increased (+58% and +52% vs. the control group), suggesting an improved glucose uptake. The phosphorylated-Akt/total Akt ratio was significantly enhanced in the PT30 group (+25%), and therefore a more efficient translocation of GLUT4 is likely. Additionally, in this group the amount of cardiotrophin-1 was significantly increased (+65%). These data suggest that the effect of Pterostilbene on Akt is mediated by this cytokine. In the liver, glucokinase activity was significantly increased only in the PT15 group (+34%), and no changes were observed in glucose-6-phosphatase activity. The beneficial effect of Pterostilbene on glycaemic control was more evident with the lower dose, probably because in the PT15 group both the muscle and the liver were contributing to this effect, but in the PT30 group only the skeletal muscle was responsible.
CONCLUSIONS:
In conclusion, Pterostilbene improves glycaemic control in rats showing insulin resistance induced by an obesogenic diet. An increase in hepatic glucokinase activity, as well as in skeletal muscle glucose uptake, seems to be involved in the anti-diabetic effect of this phenolic compound. | | Apoptosis. 2012 Jan;17(1):25-36. | | Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo.[Pubmed: 21928089 ] | Vascular endothelial cell (VEC) apoptosis is the main event occurring during the development of atherosclerosis. Pterostilbene (PT), a natural dimethylated analog of resveratrol, has been the subject of intense research in cancer and inflammation. However, the protective effects of PT against oxidized low-density lipoprotein (oxLDL)-induced apoptosis in VECs have not been clarified.
METHODS AND RESULTS:
We investigated the anti-apoptotic effects of PT in vitro and in vivo in mice. PT at 0.1-5 μM possessed antioxidant properties comparable to that of trolox in a cell-free system. Exposure of human umbilical vein VECs (HUVECs) to oxLDL (200 μg/ml) induced cell shrinkage, chromatin condensation, nuclear fragmentation, and cell apoptosis, but PT protected against such injuries. In addition, PT injection strongly decreased the number of TUNEL-positive cells in the endothelium of atherosclerotic plaque from apoE(-/-) mice. OxLDL increased reactive oxygen species (ROS) levels, NF-κB activation, p53 accumulation, apoptotic protein levels and caspases-9 and -3 activities and decreased mitochondrial membrane potential (MMP) and cytochrome c release in HUVECs. These alterations were attenuated by pretreatment with PT. PT inhibited the expression of lectin-like oxLDL receptor-1 (LOX-1) expression in vitro and in vivo. Cotreatment with PT and siRNA of LOX-1 synergistically reduced oxLDL-induced apoptosis in HUVECs. Overexpression of LOX-1 attenuated the protection by PT and suppressed the effects of PT on oxLDL-induced oxidative stress. PT may protect HUVECs against oxLDL-induced apoptosis by downregulating LOX-1-mediated activation through a pathway involving oxidative stress, p53, mitochondria, cytochrome c and caspase protease.
CONCLUSIONS:
PT might be a potential natural anti-apoptotic agent for the treatment of atherosclerosis. |
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