Activity of Pterostilbene Metabolites against Liver Steatosis in Cultured Hepatocytes

Pterostilbene is a dimethyl ether derivative of resveratrol, less metabolized than its analogue, due to the substitution of two hydroxyl groups with methoxyl groups. Nevertheless, the amounts of pterostilbene phase II metabolites found in plasma and tissues are higher than those of the parent compound. The first aim of this study was to assess whether pterostilbene-4′-O-glucuronide (PT-G) and pterostilbene-4′-O-sulfate (PT-S) were able to prevent triglyceride accumulation in AML12 (alpha mouse liver 12) hepatocytes. This being the case, we aimed to analyze the mechanisms involved in their effects. For this purpose, an in vitro model mimicking the hepatocyte situation in fatty liver was developed by incubating mouse AML12 hepatocytes with palmitic acid (PA). For cell treatments, hepatocytes were incubated with 1, 10 or 25 µM of pterostilbene, pterostilbene-4′-O-glucuronide or pterostilbene-4′-O-sulfate for 18 h. Triglycerides and cell viability were assessed by a commercial kit and crystal violet assay, respectively. Protein expression of enzymes and transporters involved in triglyceride metabolism was analyzed by immunoblot. The results showed for the first time the anti-steatotic effect of pterostilbene metabolites and thus, that they contribute to the preventive effect induced by pterostilbene on steatosis in in vivo models. This anti-steatotic effect is mainly due to the inhibition of de novo lipogenesis.This research was funded by Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (grant number AGL-2015-65719-R MINECO/FEDER, UE), Instituto de Salud Carlos III CIBERobn (grant number CB12/03/30007) and University of the Basque Country (grant number GIU 18/173)

Pterostilbene induces cell cycle arrest and apoptosis in MOLT4 human leukemia cells

Pterostilbene, a polyphenolic compound present in grapes and other fruits, has been demonstrated to inhibit growth and induce apoptosis and autophagy in some cancer cell types. We found that pterostilbene at the IC90 concentration of 44 µM inhibited proliferation and induced apoptosis in MOLT4 human leukemia cells. Treatment with pterostilbene resulted in a transient accumulation of cells in the G0/G1-cell cycle phase followed by the S-phase arrest. Pterostilbene-induced apoptotic death of MOLT4 cells was mediated by caspase-3 activation and was accompanied by the disruption of mitochondrial membrane potential, phosphatidylserine externalization and internucleosomal DNA fragmentation. Our results suggest that pterostilbene could serve as a potential additional chemotherapeutic agent for the treatment of leukemia

Accessing The Bioavailability Of Phytochemicals In Caco-2 Cell Model And Developing A Sensitive Method For The Detection And Quantification Of These Compounds

Numerous studies have found certain unmethylated phytochemicals to possess anti-carcinogenic activity; however, they have been associated with poor oral bioavailability which is a major limiting factor in their usage in chemopreventative treatment. The purpose of this study was to investigate if methylation of a compound would affect bioavailability, in terms of transport and permeability, in a Caco-2 cell model as well as the effect of cell viability and cellular uptake in human colon cancer cell lines. Furthermore, a new analytic method using reversed-phase high performance liquid chromatography coupled with electrochemical detector (HPLC-EC) for the detection and quantification of resveratrol and pterostilbene was developed. This new method was simple, rapid, and more sensitive compared to other detection methods used to analyze resveratrol and pterostilbene. Linear range, limit of detection (LOD), precision and recovery were used to validate this new analytical method. There was a significant increase in intracellular uptake and stronger growth inhibitory of pterostilbene in human cancer cells lines in comparison to resveratrol. Resveratrol exhibited a higher and more rapid rate of transport than pterostilbene across the Caco-2 monolayer regardless of the concentration tested and direction. Pterostiblene exhibited little difference in the rate of transport from either direction. The HCT-116 colon cells had intracellular uptake of each of the polymethoxyflavones (PMFs) tested. Transport was observed by all the PMFs and each had different rates of transport. Overall, location and amount of methyl groups had an effect on bioavailablity of a compound and these compounds show promise as chemopreventative agents

Stilbenes: Characterization, bioactivity, encapsulation and structural modifications. A review of their current limitations and promising approaches

©2022. This manuscript version is made available under the CC-BY-NC 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted, version of a Published Work that appeared in final form in Critical Reviews in Food Science and Nutrition. To access the final edited and published work see https://doi.org/10.1080/10408398.2022.2045558Stilbenes are phenolic compounds naturally synthesized as secondary metabolites by the shikimate pathway in plants. Research on them has increased in recent years due to their therapeutic potential as antioxidant, antimicrobial, anti-inflammatory, anticancer, cardioprotective and anti-obesity agents. Amongst them, resveratrol has attracted the most attention, although there are other natural and synthesized stilbenes with enhanced properties. However, stilbenes have some physicochemical and pharmacokinetic problems that need to be overcome before considering their applications. Human clinical evidence of their bioactivity is still controversial due to this fact and hence, exhaustive basis science on stilbenes is needed before applied science. This review gathers the main physicochemical and biological properties of natural stilbenes, establishes structure-activity relationships among them, emphasizing the current problems that limit their applications and presenting some promising approaches to overcome these issues: the encapsulation in different agents and the structural modification to obtain novel stilbenes with better features. The bioactivity of stilbenes should move from promising to evident

Resveratrol and Pterostilbene, Two Analogue Phenolic Compounds, Affect Aquaglyceroporin Expression in a Different Manner in Adipose Tissue

Aquaglyceroporins (AQPs) are transmembrane channels that mediate glycerol release and glycerol uptake. They are involved in fat metabolism, with implications in obesity. The aim was to determine whether the administration of resveratrol and pterostilbene during the six weeks of the experimental period would modify AQPs expression in white and brown adipose tissues from Wistar rats fed an obesogenic diet, and to establish a potential relationship with the delipidating properties of these compounds. Consequently, thirty-six rats were divided into four groups: (a) group fed a standard diet; and three more groups fed a high-fat high-sucrose diet: (b) high-fat high-sucrose group: (c) pterostilbene-treated group (30 mg/kg/d): (d) resveratrol-treated group (30 mg/kg/d). Epididymal, subcutaneous white adipose tissues and interscapular brown adipose tissue were dissected. AQPs gene expression (RT-PCR) and protein expression (western-blot) were measured. In white adipose tissue, pterostilbene reduced subcutaneous adipose tissue weight and prevented the decrease in AQP9 induced by obesogenic feeding, and thus glycerol uptake for triglyceride accumulation. Resveratrol reduced epididymal adipose tissue weight and avoided the decrease in AQPs related to glycerol release induced by high-fat high-sucrose feeding, suggesting the involvement of lipolysis in its body-fat lowering effect. Regarding brown adipose tissue, AQP7 seemed not to be involved in the previously reported thermogenic activity of both phenolic compounds.This research has been supported by MINECO (AGL-2015-65719), Instituto de Salud Carlos III (CIBERobn) and Basque Government (IT-572-13; PA18/03)

Chemopreventive Effects of Pterostilbene in Metastatic Prostate Cancer Cells

Recent studies find that pterostilbene (PTS) exhibits more favorable drug properties and similar chemopreventive effects to its structural analogue resveratrol (RSV). However, few studies describe the activity of PTS in prostate cancer (PCa). Here, we conducted cell count experiments to assess the effects of PTS on metastatic PCa cell viability and to compare the potency of PTS to RSV in this respect. We also performed experiments to assess the effects of PTS on the androgen receptor (AR) and AR-mediated events. We used qPCR to measure the mRNA levels of the androgenresponsive gene (ARG), prostate-specific antigen (PSA), and Western blots to assess the expression and subcellular localization of the AR protein in LNCaP cells. We found that PTS inhibited cell viability more potently than RSV in androgen-dependent LNCaP and androgen-independent PC-3 cells. These inhibitory effects were time and dosedependent and suggest that PTS may provide chemopreventive effects at multiple stages of disease. PTS also inhibited androgen-induced PSA mRNA levels in LNCaP cells. However, this inhibitory effect could not be fully attributed to changes in the androgeninduced expression or nuclear translocation of AR protein. Therefore, further investigation is required to elucidate PTS’s effects on AR-mediated events and to assess the clinical applicability of PTS in PCa

Biological actions and molecular effects of resveratrol, pterostilbene, and 3′-hydroxypterostilbene

AbstractStilbenes are a class of polyphenolic compounds, naturally found in a wide variety of dietary sources such as grapes, berries, peanuts, red wine, and some medicinal plants. There are several well-known stilbenes including trans-resveratrol, pterostilbene, and 3′-hydroxypterostilbene. The core chemical structure of stilbene compounds is 1,2-diphenylethylene. Recently, stilbenes have attracted extensive attention and interest due to their wide range of health-beneficial effects such as anti-inflammation, -carcinogenic, -diabetes, and -dyslipidemia activities. Moreover, accumulating in vitro and in vivo studies have reported that stilbene compounds act as inducers of multiple cell-death pathways such as apoptosis, cell cycle arrest, and autophagy for chemopreventive and chemotherapeutic agents in several types of cancer cells. The aim of this review is to highlight recent molecular findings and biological actions of trans-resveratrol, pterostilbene, and 3′-hydroxypterostilbene

调控53BP1-P53 复合物提升紫檀芪抑制肺癌侵袭转移研究

Pterostilbene is a natural resveratrol dimethylated analogue that has anticancer effects against a variety of cancers. It has better and oral absorption than resveratrol. In this paper, the molecular mechanism of p53-53BP1 complex regulating pterostilbene on the proliferation of lung cancer cells was elaborated from the aspects of the regulatory mechanism of pterostilbene on lung cancer cells