Stilbenoid pterostilbene complexed with cyclodextrin preserves left ventricular function after myocardial infarction in rats: possible involvement of thiol proteins and modulation of phosphorylated GSK-3β

Preshaw

et al. 2020

Sci Rep

tan 1 ✉ Resveratrol (RES) is a natural polyphenol with potential as an adjunctive therapeutic modality for periodontitis. However, its inferior pharmacokinetics and toxicity concerns about its commonly used solvent dimethyl sulfoxide (DMSO) hinder translation to clinical applicability. Our study aimed to investigate the comparative antimicrobial properties of RES and its analogues (pterostilbene [PTS], oxyresveratrol [OXY] and piceatannol [PIC]), utilizing 2-hydroxypropyl-β-cyclodextrin (HpβCD) as a solubiliser, which has a well-documented safety profile and FDA approval. These properties were investigated against Fusobacterium nucleatum, a key periodontal pathogen. PTS demonstrated the most potent antibacterial effects in HPβCD, with MIC > 60-fold lower than that of RES, OXY and PIC. In addition, PTS inhibited F. nucleatum biofilm formation. PTS exerted antimicrobial effects by eliciting leakage of cellular contents, leading to loss of bacterial cell viability. PTS also conferred immunomodulatory effects on F. nucleatum-challenged macrophages via upregulation of antioxidant pathways and inhibition of NF-κB activation. Given the superior antimicrobial potency of PTS against F. nucleatum compared to RES and other analogues, and coupled with its immunomodulatory properties, ptS complexed with HpβCD holds promise as a candidate nutraceutical for the adjunctive treatment of periodontitis.

Section: Discussionsupporting

confidence: 92%

Pterostilbene complexed with cyclodextrin exerts antimicrobial and anti-inflammatory effects

Preshaw

et al. 2020

Sci Rep

“…Like resveratrol, pterostilbene functions as a potent antioxidant and exerts myocardial protection [7]. Previous studies reported that pterostilbene could preserve cardiac function against hypertrophy, myocardial infarction and ischemia reperfusion injury via oxidative stress inhibition [7, 8, 10]. Interestingly, our present study found that pterostilbene application significantly reduced DOX-induced injury on H9c2 cells.…”

Section: Discussionsupporting

confidence: 56%

“…Pterostilbene is a natural demethylated analogue of resveratrol and riches in blueberries and grapes [30]. Like resveratrol, pterostilbene functions as a potent antioxidant and exerts myocardial protection [7]. Previous studies reported that pterostilbene could preserve cardiac function against hypertrophy, myocardial infarction and ischemia reperfusion injury via oxidative stress inhibition [7, 8, 10].…”

Section: Discussionmentioning

confidence: 99%

“…Pterostilbene (3,5-dimethoxy-4′-hydroxystilbene, PTS) is a natural analog of resveratrol and a known antioxidant mainly exists in blueberries and grapes [5, 6]. A dozen of basic studies reveal that pterostilbene is a potent myocardial protective agent against various cardiac diseases, including hypertrophy, diabetic cardiomyopathy, myocardial infarction and ischemia reperfusion injury [7–10]. These favorable effects of pterostilbene application are largely attributed to the free radical scavenging and anti-inflammatory actions [11, 12].…”

Section: Introductionmentioning

confidence: 99%

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PGC1α activation by pterostilbene ameliorates acute doxorubicin cardiotoxicity by reducing oxidative stress via enhancing AMPK and SIRT1 cascades

Liu

et al. 2019

Aging

Doxorubicin (DOX) is a widely used and potent anticancer agent, but DOX dose-dependently induced cardiotoxicity greatly limits its use in clinic. Pterostilbene, a natural analog of resveratrol, is a known antioxidant and exerts myocardial protection. The present study explored the action and detailed mechanism of pterostilbene on DOX-treated cardiomyocytes. We investigated the effects of pterostilbene on established acute DOX-induced cardiotoxicity models in both H9c2 cells treated with 1 μM DOX and C57BL/6 mice with DOX (20 mg/kg cumulative dose) exposure. Pterostilbene markedly alleviated the DOX exposure-induced acute myocardial injury. Both in vitro and in vivo studies revealed that pterostilbene inhibited the acute DOX exposure-caused oxidative stress and mitochondrial morphological disorder via the PGC1α upregulation through activating AMPK and via PGC1α deacetylation through enhancing SIRT1. However, these effects were partially reversed by knockdown of AMPK or SIRT1 in vitro and treatment of Compound C (AMPK inhibitor) or EX527 (SIRT1 inhibitor) in vivo. Our results indicate that pterostilbene protects cardiomyocytes from acute DOX exposure-induced oxidative stress and mitochondrial damage via PGC1α upregulation and deacetylation through activating AMPK and SIRT1 cascades.

Oxidative Medicine and Cellular Longevity

“…The therapeutic effect of potential small-molecule inducers of Nrf2 has been studied on MI mice models. The stilbenoid pterostilbene complexed with cyclodextrin can preserve left ventricular function of MI rats by increasing the activity of GST and glutaredoxin (GRx) and the expression of Nrf2 and p-GSK-3 β [ 91 ]. Moreover, 3-n-butylphthalide (NBP), a drug used in the treatment of ischemic stroke, can inhibit OS and the inflammatory response to reduce myocardial cell death of MI rats through the AKT/Nrf2 signaling pathway [ 92 ].…”

Section: Nrf2 Signaling Pathway and Cvdmentioning

confidence: 99%

Role of Nrf2 and Its Activators in Cardiocerebral Vascular Disease

Cheng

Zhang

et al. 2020

Cardiocerebral vascular disease (CCVD) is a common disease with high morbidity, disability, and mortality. Oxidative stress (OS) is closely related to the progression of CCVD. Abnormal redox regulation leads to OS and overproduction of reactive oxygen species (ROS), which can cause biomolecular and cellular damage. The Nrf2/antioxidant response element (ARE) signaling pathway is one of the most important defense systems against exogenous and endogenous OS injury, and Nrf2 is regarded as a vital pharmacological target. The complexity of the CCVD pathological process and the current difficulties in conducting clinical trials have hindered the development of therapeutic drugs. Furthermore, little is known about the role of the Nrf2/ARE signaling pathway in CCVD. Clarifying the role of the Nrf2/ARE signaling pathway in CCVD can provide new ideas for drug design. This review details the recent advancements in the regulation of the Nrf2/ARE system and its role and activators in common CCVD development.