Natural Stilbene Research Articles

The Inhibitory Effects of the Natural Stilbene Piceatannol on Lactate Transport In Vitro Mediated by Monocarboxylate Transporters.

Lactate, a signaling molecule and energy source, crosses membranes through monocarboxylate transporters (MCTs). MCT1 and MCT4 are potential cancer drug targets due to their role in metabolic reprogramming of cancer cells. Stilbenes, plant secondary metabolites found in several food sources, have anticancer effects, though their mechanisms of action are not well understood. This study links the anticancer activity of natural stilbenes to tumor cell lactate metabolism. The impact of resveratrol, pinostilbene, pterostilbene, rhapontigenin, and piceatannol on lactate transport is studied using a fluorescence resonance energy transfer (FRET)-based lactate sensor. The viability and migration of cells expressing MCT1 or MCT4 are also evaluated. Piceatannol inhibits MCT1 effectively at low micromolar concentrations, with less effect on MCT4. All stilbenes significantly reduce cell viability and migration. These findings indicate that both MCTs are stilbene targets, with piceatannol highlighted as a cost-effective, low-toxicity compound for studying MCTs in cancer, providing a new mechanism of action of the therapeutic and nutraceutical effects of natural polyphenols. This enriches the understanding of dietary polyphenols in cancer prevention and therapy.

Piceatannol protects against myocardial ischemia/reperfusion injury by inhibiting ferroptosis via Nrf-2 signaling-mediated iron metabolism

Myocardial tissue ischemia damages myocardial cells. Although reperfusion is an effective technique to rescue myocardial cell damage, it may also exacerbate myocardial cell damage. Ferroptosis, an iron-dependent cell death, occurs following myocardial ischemia-reperfusion (I/R). Piceatannol (PCT) is a natural stilbene compound with excellent antioxidant properties that protect against I/R injury and exerts protective effects against ferroptosis-induced cardiomyocytes following I/R injury; however, the exact mechanism remains to be elucidated. PurposeThis study aims to investigate the protective effect and mechanism of PCT on myocardial ischemia-reperfusion injury. MethodsAn ischemia-reperfusion model was established via ligation of the left anterior descending branch of mice's hearts and hypoxia-reoxygenation (H/R) of cardiomyocytes. ResultsDuring ischemia-reperfusion, Nuclear factor E2-related factor 2 (Nrf-2) expression was downregulated, the left ventricular function was impaired, intracellular iron and lipid peroxidation product levels were elevated, and cardiomyocytes underwent ferroptosis. Furthermore, ferroptosis was enhanced following treatment with an Nrf-2 inhibitor. After PCT treatment, Nrf-2 expression significantly increased, intracellular ferrous ions and lipid peroxidation products significantly reduced, Ferroportin1 (FPN1) expression increased, and transferrin receptor-1 (TfR-1) expression was inhibited. ConclusionsPCT regulates iron metabolism through Nrf-2 to protect against myocardial cell ferroptosis induced by myocardial I/R injury.

Photosensitized isomerization of resveratrol: Evaluation of energy and electron transfer pathways

Resveratrol (3,5,4′-trihydroxystilbene, RSV) is a natural stilbene synthetized as trans-isomer in plants exposed to oxidative stress. In order to understand the mechanism involved during photosensitized degradation of trans-resveratrol, steady-state and time-resolved experiments were performed and compared with quantum-chemical calculations using density functional theory (DFT). Pterin (Ptr), a well-known photosensitizer, under UV-A radiation induces the oxidation of several biomolecules mainly through electron-transfer mechanisms.On the one hand, it was observed that trans-RSV participates in an energy-transfer pathway with Ptr triplet excited state (3Ptr*) forming 3trans-RSV*, which dissipates the energy by isomerization to cis-RSV. On the other hand, RSV neutral radical (trans-RSV(-H)•) was detected in laser flash photolysis experiments, evidencing an electron-transfer mechanism. The electron-transfer from 3Ptr* to trans-RSV is a barely feasible reaction, however, more favorable is the formation of trans-RSV(-H)• in a reaction between trans-RSV and Ptr radical cation (Ptr•+), which is produced during irradiation.The combination of experimental and theoretical approaches evidences the capability of trans-RSV to undergo energy-transfer (feasible by DFT calculations) and/or one-electron transfer pathways with 3Ptr*. These findings reveal the mechanisms involved in the interaction of trans-RSV and pterin excited states and provide information on the antioxidant action of resveratrol during photosensitized oxidation of biomolecules.

Pterostilbene alleviates abdominal aortic aneurysm via inhibiting macrophage pyroptosis by activating the miR-146a-5p/TRAF6 axis.

Pterostilbene (PTE), a natural stilbene found in blueberries and several varieties of grapes, has several pharmacological activities, including anti-inflammatory and antioxidative activities. However, its role in abdominal aortic aneurysm (AAA), which is a severe inflammatory vascular disease, remains incompletely understood. In this study, we investigated the protective effects of natural stilbene PTE on AAA formation and the underlying mechanism. Two AAA mouse models (Ang II-induced model and PPE-induced model) were used to examine the effect of PTE on AAA formation. We showed that PTE administration attenuated AAA formation in mice. Furthermore, we found that PTE significantly inhibited inflammatory responses in mouse aortas, as PTE suppressed macrophage pyroptosis and prevented macrophage infiltration in aortas, resulting in reduced expression of pro-inflammatory cytokines in aortas. We also observed similar results in LPS + ATP-treated Raw 264.7 cells (a macrophage cell line) and primary peritoneal macrophages in vitro. We showed that pretreatment with PTE restrained inflammatory responses in macrophages by inhibiting macrophage pyroptosis. Mechanistically, miR-146a-5p and TRAF6 interventions in vivo and in vitro were used to investigate the role of the miR-146a-5p/TRAF6 axis in the beneficial effect of PTE on macrophage pyroptosis and AAA. We found that PTE inhibited macrophage pyroptosis by miR-146a-5p-mediated suppression of downstream TRAF6 expression. Moreover, miR-146a-5p knockout or TRAF6 overexpression abrogated the protective effect of PTE on macrophage pyroptosis and AAA formation. These findings suggest that miR-146a-5p/TRAF6 axis activation by PTE protects against macrophage pyroptosis and AAA formation. PTE might be a promising agent for preventing inflammatory vascular diseases, including AAA.

Dietary supplementation of pterostilbene, a major component in small berries, prevents alcohol-induced liver injury associated with lipid accumulation and inflammation.

Pterostilbene (PTE), a natural stilbene found in small berries, exhibits multiple pharmacological activities, particularly antioxidant and anti-inflammatory activities. This study explores the dietary supplementation of PTE to ameliorate acute and chronic alcohol-associated liver disease (ALD). C57BL/6 mice were administrated with PTE and subjected to acute or chronic alcohol stimulation. They were intragastrically administered with alcohol (5 g kg-1, 3 times per 24 h) to induce acute alcohol liver injury or fed a Lieber-DeCarli liquid diet containing 5% ethanol for 4 weeks and a single binge to induce chronic alcoholic liver injury. In the acute ethanol model, PTE decreased the serum transaminase and triglyceride (TG) levels and ameliorated lipid droplet accumulation. PTE ameliorated acute ethanol-induced hepatic steatosis by inhibiting the expression of SREBP1 and its target genes and up-regulating PPARα expression. PTE could reverse the inflammatory response by inhibiting NLRP3 activation, inflammatory factor secretion, and macrophage recruitment caused by acute ethanol exposure. PTE could synergistically activate the SIRT1-AMPK and LXR/FXR axis in mice with acute ethanol exposure. In the chronic-binge ethanol feeding model, PTE also decreased serum transaminase and TG levels and ameliorated hepatocellular ballooning, macrovesicular steatosis, lipid accumulation and inflammation. Chronic-binge ethanol feeding could induce extracellular matrix dysfunction with an increase in α-SMA, collagen I and TIMP-1 expression, which was decreased by PTE. PTE increased SIRT1 expression and AMPK phosphorylation and activated the LXRs/FXR axis, which could be reduced by chronic-binge ethanol feeding. PTE could prevent liver injury caused by alcohol regardless of acute or chronic exposure. These results suggest that PTE can be utilized as a dietary health supplement to avoid ALD and promote health and quality of life.

Coumarins derived from natural methoxystilbene as oxidative stress-related disease alleviators: Synthesis and in vitro-in silico study

3,4,5-Trimethoxy-3′-hydroxy-4′-methoxystilbene (TMHMS) is an anticancer natural stilbene that targets tubulin polymerization. According to research, oxidative stress and inflammation are linked to cancer, and lowering both of these hazards may have a detrimental influence on tumor development. TMHMS was used as a building block in this investigation to generate 28 coumarins with increased medicinal value. TMHMS-COU-1, the first coumarin derivative, was activated by thionyl chloride and subsequently linked with different phenols, yielding 27 TMHMS-COU variants. This natural product was used as a reference for oxidative stress-alleviated activities such as anticancer activity against eight cancerous cellular lines, antioxidant activity on H2O2-treated human SH-SY5Y populations, and anti-inflammatory activity against three enzyme-based representatives of inflammation. TMHMS and its coumarins were tested for their impact on the normal development of three cell types as well as human erythrocyte hemolysis in biocompatibility tests. Finally, utilizing two web-based programs, the pharmacokinetic profiles of the building component and its variants were computed. The inclusion of an electron-donating group on the off-side aromatic ring directly boosted the oxidative stress-alleviated activities, according to the results. These activities were also boosted when this group occupied the para or meta position. When this aromatic ring was trisubstituted with this group type, the greatest activities were found, with the trimethoxy aromatic ring having preferential activities. In terms of biocompatibility, the synthesized coumarins showed a high level of compatibility with the tested normal cells as well as human erythrocytes. Furthermore, the in silico research confirmed the synthesized coumarins' ability to provide prospective therapeutic candidates. According to the author, the coumarin-structural change might open the way for the development of novel, powerful, and biosafe TMHMS derivatives. This work provided various insights into the structure-function connections that can direct subsequent studies on TMHMS-based derivatives.

Resveratrol-derived inhibitors of the E3 ubiquitin ligase PELI1 inhibit the metastasis of triple-negative breast cancer

Triple-negative breast cancer (TNBC), as the most challenging subtype of breast cancer, exerts highly invasive ability and metastatic nature to the lymph nodes, which is correlated with poor survival rates among patients. Pellino-1 (PELI1) is an E3 ubiquitin ligase involved in tumor invasion and metastasis, and has the potential to be developed as a novel therapeutic target for TNBC. In this study, we identified a potent inhibitor of PELI1, namely compound 3d, on the basis of natural stilbene framework through medicinal chemistry approaches. This novel PELI1 inhibitor 3d showed potent binding affinity to PELI1 (Kd 8.2 μM) in fluorescence quenching assay, and markedly interrupted the interaction of PELI1 and SNAIL/SLUG confirmed by co-immunoprecipitation. Moreover, 3d exhibited potent antitumor activity in inhibiting tumor cell migration in scratch wound healing assay without affecting cell proliferation in vitro, and down-regulated the downstream EMT-effectors of PELI1 as assessed by western blotting. In the experimental lung metastasis model, 3d showed anti-TNBC metastasis efficacy without observable toxicity in vivo.

Inhibition of influenza a virus infection by natural stilbene piceatannol targeting virus hemagglutinin.

Given the magnitude of influenza pandemics as a threat to the global population, it is crucial to have as many prevention and treatment options as possible. Piceatannol (PIC) is a tetrahydroxylated stilbenoid (trans-3,4,3',5'-tetrahydroxystilbene), also known as 3'- hydroxy resveratrol, which has demonstrated many different biological activities such as anti-inflammatory and antiviral activities. In this study, the anti-influenza A virus (IAV) activities and mechanisms of PIC in vitro and in vivo were investigated in order to provide reference for the development of novel plant-derived anti-IAV drugs. The viral plaque assay, RT-PCR and western blot assay were used to evaluate the anti-IAV effects of PIC in vitro. The anti-IAV mechanism of PIC was determined by HA syncytium assay, DARTS assay and Surface Plasmon Resonance assay. The mouse pneumonia model combined with HE staining were used to study the anti-IAV effects of PIC in vivo. PIC shows inhibition on the multiplication of both H1N1 and H3N2 viruses, and blocks the infection of H5N1 pseudovirus with low toxicity. PIC may directly act on the envelope of IAV to induce the rupture and inactivation of IAV particles. PIC can also block membrane fusion via binding to HA2 rather than HA1 and cleavage site of HA0. PIC may interact with the two residues (HA2-T68 and HA2-I75) of HA2 to block the conformational change of HA so as to inhibit membrane fusion. Importantly, oral therapy of PIC also markedly improved survival and reduced viral titers in IAV-infected mice. PIC possesses significant anti-IAV effects both in vitro and in vivo and may block IAV infection mainly through interaction with HA to block membrane fusion. Thus, PIC has the potential to be developed into a new broad-spectrum anti-influenza drug for the prevention and treatment of influenza.

Resveratrol: biology, metabolism, and detrimental role on the tumor microenvironment of colorectal cancer.

A substantial increase in colorectal cancer (CRC)-associated fatalities can be attributed to tumor recurrence and multidrug resistance. Traditional treatment options, including radio- and chemotherapy, also exhibit adverse side effects. Ancient treatment strategies that include phytochemicals like resveratrol are now widely encouraged as an alternative therapeutic option. Resveratrol is the natural polyphenolic stilbene in vegetables and fruits like grapes and apples. It inhibits CRC progression via targeting dysregulated cancer-promoting pathways, including PI3K/Akt/Kras, targeting transcription factors like NF-κB and STAT3, and an immunosuppressive tumor microenvironment. In addition, combination therapies for cancer include resveratrol as an adjuvant to decrease multidrug resistance that develops in CRC cells. The current review discusses the biology of resveratrol and explores different mechanisms of action of resveratrol in inhibiting CRC progression. Further, the detrimental role of resveratrol on the immunosuppressive tumor microenvironment of CRC has been discussed. This review illustrates clinical trials on resveratrol in different cancers, including resveratrol analogs, and their efficiency in promoting CRC inhibition.

Grapevine shoots extract as an alternative to SO2 in rosé wines. A double approach: Classical measurements and 1H NMR metabolomics

The consumption of rosé wines has increased in the recent years, largely due to their attractive color and their simplicity, elegance, and freshness. However, rosé wines can easily oxidise, turning into an orange-brownish color, which leads its rejection by consumers. It is likely that alternatives to sulfur dioxide (SO2) in rosé wines have not yet been studied for this reason. The current work investigates the use of a natural stilbene extract, glutathione and combinations of both as possible alternatives to SO2 in rosé wines. The parameters selected for the evaluation of alternatives were fermentation kinetics, enological parameters related to quality, the main phenolic compounds, glutathione, grape reaction product, and amino acids and biogenic amines. Moreover, a 1H-NMR-based metabolomics study was carried out after 12 months of bottling. The results highlighted that stilbene extract inhibits malolactic fermentation, thereby preserving rosé wine quality. However, color-related parameters, phenolic compounds (malvidin 3-glucoside, caftaric and ferulic acids), glutathione, grape reaction product and amino acids were only slightly affected by the treatments. The 1H NMR targeted metabolomic study indicated that the stilbene treatment significantly affected the contents of threonine, myo-inositol, choline, arabinose and methanol in comparison to SO2 wines. The use of glutathione did not improve the quality of the rosé wines in any case (alone or in combination with the stilbene extract). We can conclude that stilbenes could be an alternative to SO2 to preserve the quality of rosé wines.

Exploring the therapeutic potential of naturally occurring piceatannol in non-communicable diseases.

Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases.

Tetrahydroxy stilbene glycoside ameliorates neuroinflammation for Alzheimer's disease via cGAS-STING

Alzheimer's disease (AD), also known as senile dementia, is the most common degenerative disease of the central nervous system. Neuroinflammation is currently believed to be a crucial factor in the progression of AD, while its exact mechanism remains unclear. In this study, we demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation. Treating with a natural active ingredient tetrahydroxy stilbene glucoside (TSG) from the Chinese herb Polygonum multiflorum that has been well known for its unique anti-aging effect, learning-memory ability of AD mice was distinctly improved. Meanwhile, it was observed that the expressions of serum inflammatory cytokines and the activation of microglia in cerebral cortex and hippocampus were suppressed after TSG treatment, which was probably attributable to the decrease of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggered immune response and NLRP3 inflammasome activation. Furthermore, cell culture experiments employing LPS combined with IFN-γ induced microglia activation showed that TSG reversed the polarization status of M1-type microglia to restore the quiescence, and cGAS-STING elevation was observed in the activated microglia and normalized by TSG incubation. In addition, TSG suppressed the production of inflammatory cytokines such as IL-1β, IL-6, TNF-α, IFN-α and IFN-β, as well as the expression of IFN regulatory proteins such as IFIT1 and IRF7 in the LPS/IFN-γ-stimulated inflammatory response in BV2 cell. Finally, it was also verified that TSG are, in part, through a cGAS-STING dependent pathway and triggered NLRP3 inflammasome activation to inhibit neuroinflammation through interfering with cGAS-STING inhibitors. Taken together, our findings highlight the health benefits of TSG and its potential application in preventing cognitive disorders by inhibiting neuroinflammation through cGAS-STING signaling pathway in AD.

α-Viniferin-Induced Apoptosis through Downregulation of SIRT1 in Non-Small Cell Lung Cancer Cells.

α-Viniferin, a natural stilbene compound found in plants and a polymer of resveratrol, had demonstrated potential anti-cancer and anti-inflammatory effects. However, the specific mechanisms underlying its anti-cancer activity were not yet fully understood and required further investigation. This study evaluated the effectiveness of α-viniferin and ε-viniferin using MTT assay. Results showed that α-viniferin was more effective than ε-viniferin in reducing the viability of NCI-H460 cells, a type of non-small cell lung cancer. Annexin V/7AAD assay results provided further evidence that the decrease in cell viability observed in response to α-viniferin treatment was due to the induction of apoptosis in NCI-H460 cells. The present findings indicated that treatment with α-viniferin could stimulate apoptosis in cells by cleaving caspase 3 and PARP. Moreover, the treatment reduced the expression of SIRT1, vimentin, and phosphorylated AKT, and also induced AIF nuclear translocation. Furthermore, this research provided additional evidence for the effectiveness of α-viniferin as an anti-tumor agent in nude mice with NCI-H460 cell xenografts. As demonstrated by the TUNEL assay results, α-viniferin promoted apoptosis in NCI-H460 cells in nude mice.

Ultrafast non-adiabatic dynamics of stilbene-based plant-derived sunscreens with cis–trans isomerization structures

In this work, we investigated the potential UV protection mechanism of the natural compounds hydroxy resveratrol and pterostilbene by combining theoretical calculations and femtosecond transient absorption spectra (FTAS). The UV absorption spectra showed that the two compounds exhibited strong absorption properties and high photostability. We found two molecules will reach the S1 state or an even higher excited state after UV exposure and molecules in S1 will cross a lower energy barrier to reach the conical intersection. The adiabatic trans–cis isomerization process happened and finally return to the ground. Meanwhile, FTAS clarified the time scale of trans–cis isomerization of two molecules was ∼ 10 ps, which also met the requirement of fast energy relaxation. This work also provides theoretical guidance for developing new sunscreen molecules from natural stilbene.

Pterostilbene could alleviate diabetic cognitive impairment by suppressing TLR4/NF-кB pathway through microbiota-gut-brain axis.

Diabetic cognitive impairment (DCI) is a serious neurodegenerative disorder caused by diabetes, with chronic inflammation being a crucial factor in its pathogenesis. Pterostilbene is a well-known natural stilbene derivative that has excellent anti-inflammatory activity, suggesting its potential medicinal advantages for treating DCI. Therefore, this study is to explore the beneficial effects of pterostilbene for improving cognitive dysfunction in DCI mice. A diabetic model was induced by a high-fat diet plus streptozotocin (40 mg·kg-1 ) for consecutive 5 days. After the animals were confirmed to be in a diabetic state, they were treated with pterostilbene (20 or 60 mg·kg-1 , i.g.) for 10 weeks. Pharmacological evaluation showed pterostilbene could ameliorate cognitive dysfunction, regulate glycolipid metabolism disorders, improve neuronal damage, and reduce the accumulation of β-amyloid in DCI mice. Pterostilbene alleviated neuroinflammation by suppressing oxidative stress and carbonyl stress damage, astrocyte and microglia activation, and dopaminergic neuronal loss. Further investigations showed that pterostilbene reduced the level of lipopolysaccharide, modulated colon and brain TLR4/NF-κB signaling pathways, and decreased the release of inflammatory factors, which in turn inhibited intestinal inflammation and neuroinflammation. Furthermore, pterostilbene could also improve the homeostasis of intestinal microbiota, increase the levels of short-chain fatty acids and their receptors, and suppress the loss of intestinal tight junction proteins. In addition, the results of plasma non-targeted metabolomics revealed that pterostilbene could modulate differential metabolites and metabolic pathways associated with inflammation, thereby suppressing systemic inflammation in DCI mice. Collectively, our study found for the first time that pterostilbene could alleviate diabetic cognitive dysfunction by inhibiting the TLR4/NF-κB pathway through the microbiota-gut-brain axis, which may be one of the potential mechanisms for its neuroprotective effects.

Neuroprotective Effects of Piceatannol on Olfactory Bulb Injury after Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) accounts for 5% of all stroke cases and is responsible for significant permanent brain and neurological damage within the first few days. Loss of smell is one of those neurological disorders following olfactory bulb injury after SAH. Olfaction plays a critical role in several aspects of life. The primary underlying mechanism of olfactory bulb (OB) injury and loss of smell after SAH remains unknown. Piceatannol (PIC), a natural stilbene, possesses anti-inflammatory and anti-apoptotic effects against various diseases. In this study, we aimed to investigate the potential therapeutic effects of PIC on OB injury following SAH at molecular mechanism based on SIRT1, inflammatory (TNF-α, IL1-β, NF-κB, IL-6, TLR4), and apoptosis (p53, Bax, Bcl-2, caspase-3)-related gene expression markers and histopathology level; 27 male Wistar Albino rats were used in a pre-chiasmatic subarachnoid hemorrhage model. Animals were divided into groups (n = 9): SHAM, SAH, and PIC. Garcia's neurological examination, brain water content, RT-PCR, histopathology, and TUNEL analyses were performed in all experimental groups with OB samples. Our results indicated that PIC administration significantly suppressed inflammatory molecules (TNF-α, IL-6, IL1-β, TLR4, NF-κB, SIRT1) and apoptotic molecules (caspase-3, p53, Bax). We also evaluated edema levels and cell damage in OB injury after SAH. Ameliorative effects of PIC are also observed at the histopathology level. Garcia's neurological score test performed a neurological assessment. This study is the first to demonstrate the neuroprotective effects of PIC on OB injury after SAH. It suggests that PIC would be a potential therapeutic agent for alleviating OB injury after SAH.

Pterostilbene-Mediated Inhibition of Cell Proliferation and Cell Death Induction in Amelanotic and Melanotic Melanoma.

Melanoma is one of the fastest-growing cancers worldwide. Treatment of advanced melanoma is very difficult; therefore, there is growing interest in the identification of new therapeutic agents. Pterostilbene is a natural stilbene that has been found to have several pharmacological activities. The aim of this study was to evaluate the influence of pterostilbene on the proliferation and apoptosis of human melanoma cells. Proliferation of pterostilbene-treated amelanotic (C32) and melanotic (A2058) melanoma cells was determined by BRDU assay. Flow cytometric analyses were used to determine cell cycle progression, and further molecular investigations were performed using real-time RT-qPCR. The expression of the p21 protein and the DNA fragmentation assay were determined by the ELISA method. The results revealed that pterostilbene reduced the proliferation of both amelanotic and melanotic melanoma cells. Pterostilbene induced apoptosis in amelanotic C32 melanoma cells, and this effect was mediated by an increase in the expression of the BAX, CASP9, and CASP9 genes; induction of caspase 3 activity; and DNA degradation. Pterostilbene did not affect the activation of apoptosis in the A2058 cell line. It may be concluded that pterostilbene has anticancer potential against human melanoma cells; however, more studies are still needed to fully elucidate the effects of pterostilbene on amelanotic and melanotic melanoma cells.

Mechanism of Synergy between Piceatannol and Ciprofloxacin against Staphylococcus aureus

Piceatannol (PIC) is a natural stilbene extracted from grape skins that exhibits biological activities such as antibacterial, antitumor, and antioxidant activities. The present study was carried out to further investigate the effect of PIC on the antibacterial activity of different antibiotics and to reveal the antibacterial mechanism of PIC. We found that PIC had an inhibitory effect against Staphylococcus aureus (S. aureus); its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 128 μg/mL and 256 μg/ mL, respectively. Additionally, we measured the fractional inhibitory concentration (FIC) of PIC combined with antibiotics via the checkerboard method. The results showed that when PIC and ciprofloxacin (CIP) were combined, they displayed a synergistic effect against S. aureus. Moreover, this synergistic effect was verified by time-kill assays. Further, the results of the membrane permeability assay and proton motive force assay revealed that PIC could enhance the sensitivity of S. aureus to CIP by dissipating the bacterial proton motive force (PMF), particularly the ∆ψ component, rather than increasing membrane permeability. PIC also inhibited bacterial adenosine triphosphate (ATP) synthesis and was less likely to induce bacterial resistance but exhibited slight hemolytic activity on mammalian erythrocytes. In summary, the combination of PIC and CIP is expected to become a new drug combination to combat S. aureus.

Pterostilbene attenuates intrauterine growth retardation-induced colon inflammation in piglets by modulating endoplasmic reticulum stress and autophagy

BackgroundEndoplasmic reticulum (ER) stress and autophagy are implicated in the pathophysiology of intestinal inflammation; however, their roles in intrauterine growth retardation (IUGR)-induced colon inflammation are unclear. This study explored the protective effects of natural stilbene pterostilbene on colon inflammation using the IUGR piglets and the tumor necrosis factor alpha (TNF-α)-treated human colonic epithelial cells (Caco-2) by targeting ER stress and autophagy.ResultsBoth the IUGR colon and the TNF-α-treated Caco-2 cells exhibited inflammatory responses, ER stress, and impaired autophagic flux (P < 0.05). The ER stress inducer tunicamycin and the autophagy inhibitor 3-methyladenine further augmented inflammatory responses and apoptosis in the TNF-α-treated Caco-2 cells (P < 0.05). Conversely, pterostilbene inhibited ER stress and restored autophagic flux in the IUGR colon and the TNF-α-treated cells (P < 0.05). Pterostilbene also prevented the release of inflammatory cytokines and nuclear translocation of nuclear factor kappa B p65, reduced intestinal permeability and cell apoptosis, and facilitated the expression of intestinal tight junction proteins in the IUGR colon and the TNF-α-treated cells (P < 0.05). Importantly, treatment with tunicamycin or autophagosome-lysosome binding inhibitor chloroquine blocked the positive effects of pterostilbene on inflammatory response, cell apoptosis, and intestinal barrier function in the TNF-α-exposed Caco-2 cells (P < 0.05).ConclusionPterostilbene mitigates ER stress and promotes autophagic flux, thereby improving colon inflammation and barrier dysfunction in the IUGR piglets and the TNF-α-treated Caco-2 cells.

Stilbene B10 induces apoptosis and tumor suppression in lymphoid Raji cells by BTK-mediated regulation of the KRAS/HDAC1/EP300/PEBP1 axis

Lymphoma is a cancer of the lymphoid cells that originated in matured B or T cells. The bioactive natural compounds can efficiently treat this disease with lesser side effects. Thus, in this study, a natural stilbene B10 (3-methoxy 5-hydroxy stilbene) isolated from Cajanus cajan (Pigeon Pea) was screened for its anti-proliferative efficacy against 13 cancer cell lines. B10 showed a potential effect on the human lymphoma (Raji) cells. Cytotoxicity analysis of B10 has revealed IC50 concentrations in Raji cells at low doses (18 µM) than other cancer cell lines. The B10 could significantly cause dose and time-dependent inhibition in the proliferation of Raji cells triggering intrinsic apoptosis and S/G1 phase cellular arrest. There was an increased expression of phospho-γ-H2A.X and decreased expression of cyclin D1, causing DNA damage and cell cycle arrest, post- B10 treatments. The mitochondrial membrane potential (MMP) variations observed after B10 treatment led to changes in Bax/Bcl-2 ratio, cytochrome C release, and enhanced expression of cleaved caspase3, 9, PARP-1, and APAF-1. The B10 inhibited the proliferation of Raji cells by significantly downregulating the expression of KRAS, BTK, MDM2, P-JAK2, P-STAT3, PI3K, HDAC1/2, SIRT7, and EP300. The treatment upregulated the tumor suppressor genes PEBP1 and SAP18. Thus, the study could reveal the selective inhibitory effects of B10 on lymphoma, suggesting it as a probable innovative chemotherapeutic agent.