What is pterostilbene used for

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Evid Based Complement Alternat Med. Epub Jun Analysis of safety from a human clinical trial with pterostilbene. J Toxicol. Epub Feb 4. Anti-inflammatory action of pterostilbene is mediated through the p38 mitogen-activated protein kinase pathway in colon cancer cells.

Cancer Prev Res Phila. Resveratrol, pterostilbene, and piceatannol in vaccinium berries. J Agric Food Chem. Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. Amarnath Satheesh M, Pari L. Pterostilbene's ability to increase antioxidant activity by altering expression and enzymatic activity of MnSOD contributes to its credence as an anticancer agent because numerous studies show that pancreatic cancer cells have decreased expression of MnSOD when compared to normal cells and overexpression of MnSOD correlates with decreased pancreatic tumor volume [ 65 — 68 ].

In experiments conducted by Kostin et al. In addition to inhibiting pancreatic cancer, recent research found that pterostilbene ameliorated inflammation and acinar damage in pancreatitis in vitro [ 70 ]. The collective findings indicate pterostilbene's clinical relevance in the treatment of pancreatic disease. Further studies are warranted to examine the mechanisms involved in pterostilbene-induced antioxidant activity and inhibition of pancreatitis and pancreatic cancer in clinical trials.

Diabetes mellitus DM is a disease that consists of ineffective insulin regulation leading to derangements in carbohydrate, protein, and fat metabolism [ 71 ]. Over recent decades, the incidence of DM has increased worldwide due to sedentary lifestyle and the rising epidemic of obesity [ 72 ].

Lifestyle modification is one strategy employed to treat DM and associated complications; however, failure to respond to lifestyle modification is an indication for medical treatment [ 71 ]. Unfortunately, treatment with medical agents may have significant side effects, and multiple adjustments may become necessary to achieve positive clinical results. Therefore, the pursuit of new medical agents with minimal side effects remains an enviable option for the successful treatment of DM.

The heartwood of the plant Pterocarpus marsupium PM has been shown to exhibit antiglycemic properties in multiple studies. In a study performed by Grover et al. The authors hypothesized that PM treatment would counteract the metabolic side effects of a high-fructose diet by mitigating hyperglycemia, hyperinsulinemia and hypertriglycemia. Results of the study show that rats fed high-fructose diets combined with PM treatment had lower levels of hyperinsulinemia, hypertriglycemia, and complete prevention of hyperglycemia.

It has been hypothesized that the antiglycemic properties possessed by PM are attributed to pterostilbene. Further studies were conducted by Pari and Satheesh evaluating the antiglycemic effects of pterostilbene in combination with its antioxidant effect in rodent models of STZ-induced DM [ 75 , 76 ].

It was also discovered that pterostilbene treatment reduced glycosylated hemoglobin HbA1c , a marker of chronic hyperglycemia, and decreased expression of the gluconeogenic enzymes glucosephosphatase and fructose-1, 6-biphosphatase. In addition, pterostilbene increased expression of the glycolytic enzyme hexokinase.

One proposed mechanism for the antidiabetic effects exerted by pterostilbene is reduction of OS, which plays a critical role in aberrant glucose regulation.

Satheesh and Pari hypothesized that pterostilbene treatment in diabetic rats would increase antioxidant activity and lessen the impact of OS on kidney and liver cells [ 76 ]. Results of the experiments show that DM control rats exhibited marked increases in TBARS and HP in liver and kidney tissue that was subsequently inhibited by pterostilbene treatment [ 76 ].

HP expression in liver and kidney was also significantly decreased by pterostilbene treatment by Moreover, histopathological examination of the livers of pterostilbene treated DM rats did not show inflammation compared to the DM controls, which exhibited significant portal triad inflammation. Examination of diabetic rat kidneys revealed glomeruli mesangial capillary proliferation with tubular epithelial damage that was significantly reduced in DM rats treated with pterostilbene.

Comparable antioxidant and histopathological results were observed in DM rats treated with metformin suggesting that pterostilbene may harbor clinically significant metabolic properties. The reported antioxidant and antihyperglycemic activities of pterostilbene may confer a protective effect against complications in poorly controlled DM patients by preventing hyperglycemia and associated liver and kidney damage.

The exact relationship between antioxidant activity and glucose regulation induced by pterostilbene treatment has not been elucidated; however, it is postulated that pterostilbene increases antioxidant activity leading to improved glucose metabolism. Increased antioxidant activity produced by pterostilbene may improve tissue resilience against hyperglycemia-generated ROS and prevent end-organ damage. The human applicability of pterostilbene's antidiabetic effects is still unknown.

Nemes-Nagy et al. It is possible that such results are attributable to the antioxidant activity of pterostilbene; however, additional studies are needed to identify the blueberry-derived mediator and investigate a plausible association with pterostilbene. In addition to mitigating hyperglycemia, pterostilbene in vitro and in vivo has shown benefits in models of lipid metabolism. In 3T3-L1 preadipocytes, pterostilbene treatment decreased cell population growth, fat droplet formation, and triacylglycerol accumulation [ 78 ].

Furthermore, pterostilbene demonstrated antiobesity properties by upregulating adiponectin and downregulating leptin, indicating an antilipogenic effect [ 79 ]. Expression of adiponectin negatively correlates with body mass index BMI , glucose, insulin, and triacylglycerol levels in comparison to leptin, which positively correlates with adipocyte size, lipid content, and BMI.

Such findings are significant because derangements of glucose metabolism often accompany hyperlipidemia in diabetics and those diagnosed with metabolic syndrome.

Ultimately, the glucose and lipid-lowering effects of the dietary compound pterostilbene may contribute to its clinical potential for prevention or treatment of diabetes.

Further research is necessary to establish pterostilbene's risk-reducing and therapeutic effects in DM individuals. The aging process in humans is associated with acquired deficiencies in cognition and motor function. The process is oftentimes innocuous; however, in certain neurological conditions such as Alzheimer's Disease AD , the effects of aging are pathological and accelerated leading to rapid and permanent neurological decline [ 80 ]. Increased OS due to progressive declines in antioxidant activity is a proposed mechanism of age-related neurological deterioration in older adults [ 81 , 82 ].

Several studies show that consumption of berries rich in antioxidants may effectively thwart neurological deterioration associated with aging [ 83 , 84 ]. In an experiment conducted by Joseph et al. Bickford and colleagues examined the effect of blueberry supplementation upon antioxidant activity in aged rats along with corresponding neurological pathways and behavioral outcomes [ 86 ].

Furthermore, such changes correlate with impaired performance of motor learning and coordination. Bickford and colleagues found evidence that blueberry-fed aged rats had significant improvements in GABA potentiation and increased GSH compared to aged controls.

In addition, blueberry-fed aged rats performed rod-running motor tasks at a faster pace compared to controls. The reported findings show that blueberries contain a compound that is capable of increasing GSH antioxidant activity and cerebellar Purkinje cell GABA potentiation resulting in enhanced psychomotor performance in aged rats.

Comparable findings were obtained by Malin and colleagues who demonstrated that aged rats maintained on a 1- or 2-month blueberry diet showed significantly higher object memory recognition compared to control rats [ 87 ]. The cognitive benefits were seen after termination of the blueberry intervention diet where the 2-month blueberry diet had a longer benefit compared to the 1-month diet suggesting a time-dependent neuroprotective benefit.

Pathologic examination of the cerebellum, cortex, and hippocampal regions of blueberry fed rats that revealed significant expression of blueberry-derived polyphenolic compounds in regions important for learning and memory assessed the impact of blueberry supplementation on brain tissue [ 88 ].

The findings suggest that blueberry-derived compounds exert neuroprotective effects by crossing the blood brain barrier and altering central nervous system signals. The study results found that accumulation of polyphenolic compounds in the cortex correlated with Morris water maze MWM performance, which indicates a possible risk-reducing relationship between blueberry-derived polyphenolic compounds and memory and spatial learning abilities.

Furthermore, in experiments performed by Casadesus et al. The beneficial effects of blueberries in the modulation of neurological function may also be applicable to clinical conditions such as stroke and AD. In a study conducted by Sweeney et al.

The neuroprotective effects of a blueberry-enriched diet are numerous, and several studies have sought to identify and explain the blueberry-derived compound responsible for the multiple modulatory effects of blueberry supplementation in animal models. To determine whether pterostilbene was involved in neuroprotective outcomes, Joseph and colleagues treated aged rats with low 0.

The study results show that pterostilbene fed aged rats performed better on cognitive and motor tasks compared to controls in a dose-dependent manner. Specifically, aged rats treated with pterostilbene had higher level MWM performance, which was similarly shown in a blueberry supplementation study conducted by Andres-Lacueva and colleagues [ 88 ]. The study findings suggest that pterostilbene may be involved in modulation of neural plasticity and associated cognitive and motor functions.

Furthermore, Joseph et al. Subsequent pathological examination of hippocampal samples found detectable levels of pterostilbene in high dose fed rats but did not reveal detectable levels in low dose fed animals. Hippocampal levels of pterostilbene correlated with working memory performance that suggests that improvements in neurological function may be directly related to pterostilbene consumption.

In a study performed by Chang and colleagues, the antioxidant potential of pterostilbene was examined in the accelerated aging mouse model SAMP8 to determine a possible relationship between the antioxidant capacity of pterostilbene and neurological markers of disease [ 91 ].

Overall, the antioxidant capacity of pterostilbene has significant effects upon neurological function that may translate into clinical benefits in human subjects.

The free radical theory of aging claims that ROSs are involved in the pathogenesis of age-related neurological decline. Moreover, several studies suggest that AD results from decreased activity in major antioxidant defense systems and subsequent increased vulnerability to OS [ 80 , 81 ]. Additional research is needed to evaluate clinical outcomes associated with pterostilbene treatment in AD and other severe forms of dementia.

Epidemiological trials have shown an association between poor diets and increased risk of prostate cancer [ 97 ].

Consumption of dietary antioxidants is thought to reduce prostate cancer risk in some men by reducing inflammation and OS [ 97 ]. Specifically, blueberry juice was shown to inhibit proliferation and regulate cell cycle dysfunction in prostate cancer cells [ 16 , 17 , 58 ]. It has been postulated that the anticarcinogenic effect of blueberries in prostate cancer is predominantly a result of the anticancer mechanisms of pterostilbene.

Studies show that pterostilbene treatment inhibits prostate cancer proliferation and reduces metastatic potential. In p53 wildtype prostate cancer cells, pterostilbene prevented cell cycle progression at the G1 phase by inducing p53 expression and upregulating p21 expression maintaining tight control of proliferation; however, in p53 negative PC3 cells, pterostilbene induced apoptosis [ 94 ].

Such findings may help to explain the beneficial effects of pterostilbene in normal cells in contrast to the cytotoxic effects observed in cancerous cells. Pterostilbene treatment also modified the antioxidant activity of prostate cancer cells suggesting a possible relationship between mechanisms of oxidation and apoptosis.

Chakraborty and colleagues found that pterostilbene modified Bcl-2, Bax, and caspase 3, markers of mitochondrial apoptosis, and increased expression of the antioxidant enzymes GPx, GR, and GSH by 1. The same study also determined that pterostilbene increased levels of ROS by 5-fold, which is thought to play a role in the facilitation of mitochondrial depolarization leading to intrinsic apoptosis.

The findings demonstrate the antioxidant properties of pterostilbene in human prostate cancer cells through upregulation of the enzymes GPx, GR, and GSH. The paradoxical increase in ROS production in pterostilbene treated cells may occur through alteration of specific carcinogenic mutations present in prostate cancer that lead to programmed cell death.

The findings indicate that pterostilbene is capable of inducing apoptosis through ROS-mediated mechanism in prostate cancer cells, despite upregulation of basal antioxidant activity. Pterostilbene also decreased prostate-specific antigen PSA , a human marker of prostate malignancy, indicating potential use as a chemotherapeutic agent [ 95 ].

Currently, the preventive and chemotherapeutic potential of pterostilbene in human prostate cancer has not been established; however, the evidence suggests that pterostilbene may have alternate effects on prostate cells based upon genetic composition of each cell, becoming beneficial in the regulation of normal prostate cells and producing inhibition in cancerous cells.

Further studies are warranted to investigate the relationship between the antioxidant effects of pterostilbene and clinical outcomes in prostate cancer. The antioxidant activity of pterostilbene is an essential component of the compound's interrelated mechanisms of disease inhibition, and the studies presented in this review show that the mechanisms of pterostilbene are comparable to mechanisms exhibited by blueberry treatment in similar disease models Table 1.

The overlap is significant because blueberries are a widely consumed fruit comprised of various concentrations of pterostilbene with proven high antioxidant capacity [ 3 , 4 , 98 ]. Although it is postulated that the pterostilbene component of blueberries exerts clinical benefits, the direct correlation between pterostilbene's therapeutic effects and blueberry consumption remains undetermined.

The results presented in this review exemplify pterostilbene's complicated effect upon antioxidant activity and critical pathways of pathogenesis in multiple organ systems. The benefits of pterostilbene are vast and include neuroprotection, inhibition of malignancy, attenuation of atherosclerosis, protection against hemolysis and liver disease, and metabolic regulation of DM and hyperlipidemia.

In breast, esophageal, stomach, colon, liver, pancreatic, and prostate cancer studies, pterostilbene exhibits profound anticancer mechanisms which include reduction of proliferation rates, induction of apoptosis, alteration of the cell cycle, and inhibition of metastasis [ 5 ]. The relationship between pterostilbene and oxidation in cancer cell death has not been fully elucidated; however, it has been discovered that generation of ROS plays a significant role in the apoptotic mechanism in pterostilbene treated breast and prostate cancer cells [ 19 — 22 ].

In contrast, treatment with pterostilbene increased antioxidant activity in esophageal, pancreatic, and colon cancer models but still exerted effective anticarcinogenic effects [ 41 , 47 , 48 , 64 ]. The differences in pterostilbene's oxidative influences among cancer cell types may possibly be attributed to the distinctive daily functions of digestion which occur in the esophagus, pancreas, and colon but are absent in the breast and prostate.

Furthermore, numerous studies show that pterostilbene mechanisms vary in each disease system and are tailored toward the correction of aberrant cellular pathways and progressive dysfunction.

In disease models of aging, vascular disease, diabetes, and hemolysis, pterostilbene decreases oxidative stress most likely as a protective measure against the progressive cellular damage and dysfunction associated with disease-related deterioration [ 34 , 52 , 75 , 76 , 91 ].

Interestingly, pterostilbene treatment may upregulate or downregulate specific pathways based upon the nature of the disease process taking place. For example, pterostilbene is efficacious as an anticancer agent because it induces apoptosis in cancer cells; however, the compound has the opposite effect in the vascular system where it inhibits apoptosis in VECs thereby decreasing the risk of plaque instability [ 5 , 34 ].

Pterostilbene was also shown to exhibit comparable and synergistic effects when compared to medications used in the treatment of human disease, specifically clofibrate, metformin, Tamoxifen, and the chemotherapy regimen FOLFOX indicating that pterostilbene's therapeutic effects may be applicable if administered to human subjects [ 20 , 48 , 75 , 79 ].

Additional possible human benefits of pterostilbene include reduction of the clinical markers HbA1C in diabetes and PSA in prostate cancer which was demonstrated by Pari and Satheesh and Wang et al. However, it is unknown if the beneficial effects of pterostilbene demonstrated in vitro and in vivo occur in humans as well. The reported findings show that pterostilbene is safe for administration to humans and further contributes to our understanding of the clinical effects of pterostilbene.

Further research should include study designs aimed to delineate pterostilbene's contribution to the antioxidant effects of blueberries in diverse preclinical and clinical disease models.

Additional directions should focus upon the creation of human population studies and clinical trials to evaluate the safety and efficacy of pterostilbene in the prevention and treatment of disease. National Center for Biotechnology Information , U. Oxid Med Cell Longev. Published online Apr 4. Author information Article notes Copyright and License information Disclaimer.

Received Feb 13; Accepted Mar McCormack and D. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. Abstract Pterostilbene trans-3,5-dimethoxyhydroxystilbene is a natural dietary compound and the primary antioxidant component of blueberries.

Introduction Pterostilbene trans-3,5-dimethoxyhydroxystilbene is a naturally derived compound found primarily in blueberries and Pterocarpus marsupium PM heartwood [ 1 , 2 ].

Open in a separate window. Figure 1. Antioxidant Properties of Pterostilbene 2. Breast Increasing rates of obesity and poor nutrition are major contributors to breast cancer occurrence in women [ 14 ]. Cardiovascular Cardiovascular disease is currently the number one cause of mortality in the Unites States, and its high prevalence is attributed to multiple risk factors such as smoking, sedentary lifestyle and low intake of fruits and vegetables [ 27 ].

Gastroenterology 2. Esophagus Esophageal cancer has a poor prognosis with low rates of disease survival [ 40 ]. Stomach The risk of gastric cancer is associated with genetics and dietary factors such as high consumption of smoked, salted, and nitrated foods combined with low intake of fruits and vegetables [ 42 ]. Actively scan device characteristics for identification.

Use precise geolocation data. Select personalised content. Create a personalised content profile. Measure ad performance. Select basic ads. Create a personalised ads profile. Select personalised ads. Apply market research to generate audience insights. Measure content performance. Develop and improve products. List of Partners vendors. Pterostilbene is a compound found naturally in blueberries. It is a chemical similar to resveratrol and is available in dietary supplement form.

Preliminary research suggests that pterostilbene may reduce inflammation and offer antioxidant benefits. In mice, about half of all dietary pterostilbene has transformed into pinostilbene by the time it reaches the colon. Pinostilbene blocks the growth of human colon cancer cells, suggesting that pterostilbene supplementation may be useful against colon cancer [ 53 ].

Pterostilbene fights oxidative stress by rebalancing antioxidant enzymes. Researchers have observed this effect in human eye cells, suggesting that pterostilbene may protect from oxidative damage [ 42 ]. Some of these products even claim that sirtuin is a fountain of youth, but the truth is more complicated.

In cells, pterostilbene activates a SIRT1 signaling pathway that protects against cellular damage. This pathway increases the expression of p53 , a protein that protects the DNA and prevents mutations that could lead to cancer [ 54 , 55 ].

SIRT1 may protect against some of the degeneration and damage that takes place as we grow old. However, pterostilbene is not a magic pill against aging [ 56 ]. Multiple studies have demonstrated that pterostilbene decreases inflammation regulated by tumor necrosis factor-alpha TNF-alpha.

Oxidative stress causes inflammation; pterostilbene may block TNF-alpha and interleukin-1b IL-1b by reducing reactive oxygen species [ 33 , 57 , 58 ]. Pterostilbene also prevents stress within a part of the cellular machinery called the endoplasmic reticulum , or ER.

In one study, when cells from the lining of blood vessels were exposed to pterostilbene, their ER did not respond to inflammatory signals, and they did not become inflamed [ 57 ]. Strangely, despite decreasing endoplasmic reticulum stress in the blood vessel lining, pterostilbene actually increases ER stress in throat cancer cells. It may protect healthy cells and selectively damage cancerous cells [ 59 ].

Cancer cells use a pathway called Notch-1 to protect themselves from chemotherapy drugs, including oxaliplatin and fluorouracil. Pterostilbene appears to block Notch-1 signaling; it could, therefore, make tumors more sensitive to conventional chemotherapy [ 60 , 61 ].

Altogether, these effects reduce inflammation and make it much more difficult for cancer cells to grow [ 62 ]. Pterostilbene appears to selectively target the hippocampus region in the brain. These three proteins help neurons grow, multiply, and respond to their surroundings. SNRI antidepressants often target these pathways as well. Also in the hippocampus, pterostilbene increases a protein called Nrf2 , which in turn increases the expression of antioxidant proteins [ 25 ]. The monoamine oxidases, MAOs, are enzymes that break down neurotransmitters in the brain.

According to a recent animal study, pterostilbene inhibits MAO-B activity and, thus, increases available dopamine [ 65 , 66 , 26 ]. The precise pathway is unknown, but it appears to involve PI3K and Akt , two proteins that support memory, learning, and neuron growth [ 29 , 67 ]. Pterostilbene is considered safe and has no significant side effects up to a dose of mg per day.

Some people may have increased LDL cholesterol when taking pterostilbene; grape seed extract negates this effect and may pair well with a pterostilbene supplement [ 68 , 14 ]. There are currently no studies on the safety of pterostilbene for children or for pregnant or breastfeeding women. Because this compound is commonly found in food and considered to be healthy, small doses of pterostilbene should be safe for anyone; however, caution is advised at higher doses.

Talk to your doctor before giving pterostilbene to children or taking it yourself if you are pregnant or breastfeeding. Two studies have confirmed that pterostilbene may increase the effect of sertraline and gefitinib.

Sertraline is a selective serotonin reuptake inhibitor SSRI which is used to treat depression ; gefitinib is an epidermal growth factor receptor EGFR inhibitor which is used in chemotherapy. The combinations of pterostilbene with either sertraline or gefitinib have been studied for their anticancer effects [ 52 , 13 ].

Pterostilbene also appears to block the activity of several metabolic enzymes, most notably CYP2C8 and UGT1A6 and will increase the effect of any drug they metabolize. For CYP2C8, these include the antimalarial drug amodiaquine, cerivastatin, repaglinide, torasemide, and a few chemotherapy drugs.

For UGT1A6, these include acetaminophen and aspirin [ 69 , 70 , 71 ]. Very few studies have investigated how pterostilbene interacts with medication. However, it increases the effect of sertraline, blocks drug metabolism enzymes, and is likely to have other unstudied interactions.

To avoid adverse events and unexpected interactions, talk to your doctor before supplementing with pterostilbene. Carefully read the label and check the amount of pterostilbene per capsule before buying, as different dosages may have different effects.