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]. Furthermore, in models of hyperlipidemia, pterostilbene increased expression of PPAR-, a target for lipid lowering agents, but exerted the opposite effect in AD models where it increased PPAR-, a key modulator of neural antioxidant activity [79, 91].
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., respectively [75, 95]. However, it is unknown if the beneficial effects of pterostilbene demonstrated in vitro and in vivo occur in humans as well.
In a recent randomized double-blind placebo-controlled trial, Riche and colleagues report that 100 mg to 250 mg daily of pterostilbene in adults with hyperlipidemia did not produce significant adverse drug events [99]. In addition, treatment with 450 mg daily Pterocarpus marsupium extract in healthy volunteers did not produce signs of toxicity and resulted in detectable pterostilbene serum levels up to two weeks after administration [100]. 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.
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