Recent Advances in Synthesis, Bioactivity, and Pharmacokinetics of Pterostilbene, an Important Analog of Resveratrol

Liu, Yeju; You, Yuyang; Lü, Juan; Chen, Xi; Yang, Zhihong

doi:10.3390/molecules25215166

Cited by 72 publications

(67 citation statements)

References 94 publications

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“…Moreover, anti-inflammatory compounds have been shown to exert protective effects in the animal models of seizures/epilepsy (Elgarhi et al 2020;Singh et al 2019;Vieira et al 2016). Considering the above conditions, we speculated that the protective effect of pterostilbene in the PTZ kindling in mice might arise from its anti-inflammatory properties which were reported in the previous studies (Choo et al 2014;Lin et al 2020;Liu et al 2019Liu et al , 2020. In our study, PTZ kindling procedure triggered the inflammatory process in the brain which was manifested by up-regulation of TNF-α, IL-1β, and IL-6 mRNA levels in the prefrontal cortex and/or hippocampus of mice.…”

Section: Discussionsupporting

confidence: 68%

Anticonvulsant effect of pterostilbene and its influence on the anxiety- and depression-like behavior in the pentetrazol-kindled mice: behavioral, biochemical, and molecular studies

et al. 2021

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Rationale Pterostilbene is the 3,5-dimethoxy derivative of resveratrol with numerous beneficial effects including neuroprotective properties. Experimental studies revealed its anticonvulsant action in the acute seizure tests. Objectives The purpose of the present study was to evaluate the effect of pterostilbene in the pentetrazol (PTZ)–induced kindling model of epilepsy in mice as well as to assess some possible mechanisms of its anticonvulsant action in this model. Methods Mice were repeatedly treated with pterostilbene (50–200 mg/kg) and its effect on the development of seizure activity in the PTZ kindling was estimated. Influence of pterostilbene on the locomotor activity and anxiety- and depression-like behavior in the PTZ-kindled mice was also assessed. To understand the possible mechanisms of anticonvulsant activity of pterostilbene, γ-aminobutyric acid (GABA) and glutamate concentrations in the prefrontal cortex and hippocampus of the PTZ-kindled mice were measured using LC–MS/MS method. Moreover, mRNA expression of BDNF, TNF-α, IL-1β, IL-6, GABRA1A, and GRIN2B was determined by RT-qPCR technique. Results We found that pterostilbene at a dose of 200 mg/kg considerably reduced seizure activity but did not influence the locomotor activity and depression- and anxiety-like behavior in the PTZ-kindled mice. In the prefrontal cortex and hippocampus, pterostilbene reversed the kindling-induced decrease of GABA concentration. Neither in the prefrontal cortex nor hippocampus pterostilbene affected mRNA expression of IL-1β, IL-6, GABRA1A, and GRIN2B augmented by PTZ kindling. Pterostilbene at a dose of 100 mg/kg significantly decreased BDNF and TNF-α mRNA expression in the hippocampus of the PTZ-kindled mice. Conclusions Although further studies are necessary to understand the mechanism of anticonvulsant properties of pterostilbene, our findings suggest that it might be considered a candidate for a new antiseizure drug.

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Section: Discussionsupporting

confidence: 68%

Anticonvulsant effect of pterostilbene and its influence on the anxiety- and depression-like behavior in the pentetrazol-kindled mice: behavioral, biochemical, and molecular studies

et al. 2021

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“…Moreover, polyphenol aglycones present in the blood undergo further (and also rapid) metabolism in the liver to methylated, glucuronidated, and/or sulfated conjugates. These features, as well as the mechanisms of elimination in the urine and via the biliary tract, as well as recycling by the intestinal tract, have been reviewed in detail (e.g., Estrela 2013, Liu 2020) [ 7 , 8 ].…”

Section: Metabolism and Pharmacokineticsmentioning

confidence: 99%

“…Based on reported experimental evidence, PT has potential health benefits in inflammatory dermatoses, photoprotection, cancer prevention and therapy, insulin sensitivity, blood glycemia and lipid levels, cardiovascular diseases, aging, and memory and cognition [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Pterostilbene in Cancer Therapy

et al. 2021

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Natural polyphenols are organic chemicals which contain phenol units in their structures and possess antitumor properties. However, a key problem is their short half-life and low bioavailability under in vivo conditions. Pterostilbene (3,5-dimethoxy-4′-hydroxystilbene; PT) is a phytoalexin originally isolated from the heartwood of red sandalwood. As recently reported by our group, PT was shown to be effective in the treatment of melanoma. Counterintuitively, PT is not effective (cytotoxic) against melanoma in vitro, and only under in vivo conditions does PT display its anticancer activity. This study elucidated that PT can be effective against melanoma through the inhibition of adrenocorticotropic hormone production in the brain of a mouse, which weakens the Nrf2-dependent antioxidant defenses of melanoma and also pancreatic cancers. This results in both the inhibition of tumor growth and sensitization of the tumor to oxidative stress. Moreover, PT can promote cancer cell death via a mechanism involving lysosomal membrane permeabilization. Different grades of susceptibility were observed among the different cancer cells depending on their lysosomal heat shock protein 70 content, a known stabilizer of lysosomal membranes. In addition, the safety of PT administered i.v. has been evaluated in mice. PT was found to be pharmacologically safe because it showed no organ-specific or systemic toxicity (including tissue histopathologic examination and regular hematology and clinical chemistry data) even when administered i.v. at a high dose (30 mg/kg per day × 23 days). Moreover, new pharmacological advances are being developed to increase its bioavailability and, thereby, its bioefficacy. Therefore, although applications of PT in cancer therapy are just beginning to be explored, it represents a potential (and effective) adjuvant/sensitizing therapy which may improve the results of various oncotherapies. The aim of this review is to present and discuss the results that in our opinion best support the usefulness of PT in cancer therapy, making special emphasis on the in vivo evidence.

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“…They share a common structure generally constituted by a C6‐C2‐C6 unit, i. e. a 1,2‐diphenylethylene moiety, with aromatic rings carrying one or more hydroxy groups. In the last decades, stilbenoids have been largely studied because of their diverse bioactivities, comprising cardioprotection, neuroprotection, anti‐diabetic and anti‐inflammatory properties, cancer prevention and treatment, [6] with trans ‐resveratrol and its methoxylated analogue trans ‐pterostilbene (Figure 1A, B) being the most deeply investigated compounds of this family [7–11] …”

Section: Introductionmentioning

confidence: 99%

Plant‐Derived Stilbenoids as DNA‐Binding Agents: From Monomers to Dimers

Platella

Mazzini

Napolitano

et al. 2021

Chemistry A European J

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Stilbenoids are natural compounds endowed with several biological activities, including cardioprotection and cancer prevention. Among them, (±)‐trans‐δ‐viniferin, deriving from trans‐resveratrol dimerization, was investigated in its ability to target DNA duplex and G‐quadruplex structures by exploiting NMR spectroscopy, circular dichroism, fluorescence spectroscopy and molecular docking. (±)‐trans‐δ‐Viniferin proved to bind both the minor and major grooves of duplexes, whereas it bound the 3’‐ and 5’‐ends of a G‐quadruplex by stacking on the outer quartets, accompanied by rearrangement of flanking residues. Specifically, (±)‐trans‐δ‐viniferin demonstrated higher affinity for the investigated DNA targets than its monomeric counterpart. Additionally, the methoxylated derivatives of (±)‐trans‐δ‐viniferin and trans‐resveratrol, i. e. (±)‐pterostilbene‐trans‐dihydrodimer and trans‐pterostilbene, respectively, were evaluated, revealing similar binding modes, affinities and stoichiometries with the DNA targets as their parent analogues. All tested compounds were cytotoxic at μM concentration on several cancer cell lines, showing DNA damaging activity consistent with their ability to tightly interact with duplex and G‐quadruplex structures.

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Recent Advances in Synthesis, Bioactivity, and Pharmacokinetics of Pterostilbene, an Important Analog of Resveratrol

Cited by 72 publications

References 94 publications

Anticonvulsant effect of pterostilbene and its influence on the anxiety- and depression-like behavior in the pentetrazol-kindled mice: behavioral, biochemical, and molecular studies

Anticonvulsant effect of pterostilbene and its influence on the anxiety- and depression-like behavior in the pentetrazol-kindled mice: behavioral, biochemical, and molecular studies

Pterostilbene in Cancer Therapy

Plant‐Derived Stilbenoids as DNA‐Binding Agents: From Monomers to Dimers

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