Stilbenes: A new strategy for protecting light-sensitive foods, a review of their structure classification and singlet oxygen quenching mechanism.

Natural stilbenes have been studied extensively as a result of their complicated structures and diverse biological activities. Singlet oxygen (1O2), a kind of reactive oxygen species (ROS) has a strong destructive effect on food systems (especially for light-sensitive foods). Many cutting-edge scientific studies have found that some stilbenes not only have extensive quenching properties for ROS, but also can selectively quench 1O2. However, the industry devoted too much energy on the development of more new stilbenes, lacking in-depth summaries and reflections on the characteristics of their basic structure and the mechanism of their extraordinary 1O2 quenching abilities. Therefore, we summarized the classification methods for stilbene compounds and evaluated similarities, differences and possible limitations of different classification methods. In addition, we described the role of different functional groups in stilbenes in quenching of 1O2 and summarized the quenching mechanism of 1O2 by stilbenes. By the way, the current application of stilbene compounds and their potential risks in the food industry were also mentioned in this article. The stilbenes can be used as antioxidants (especially new strategies against 1O2 oxidation) in food systems to improve the shelf life. At this stage, it is necessary to develop more effective and safe food antioxidant stilbenes based on their quenching mechanism.

Stilbene Compounds Inhibit Tumor Growth by the Induction of Cellular Senescence and the Inhibition of Telomerase Activity.

: Cellular senescence is a state of cell cycle arrest characterized by a distinct morphology, gene expression pattern, and secretory phenotype. It can be triggered by multiple mechanisms, including those involved in telomere shortening, the accumulation of DNA damage, epigenetic pathways, and the senescence-associated secretory phenotype (SASP), and so on. In current cancer therapy, cellular senescence has emerged as a potent tumor suppression mechanism that restrains proliferation in cells at risk for malignant transformation. Therefore, compounds that stimulate the growth inhibition effects of senescence while limiting its detrimental effects are believed to have great clinical potential. In this review article, we first review the current knowledge of the pro- and antitumorigeneic functions of senescence and summarize the key roles of telomerase in the regulation of senescence in tumors. Second, we review the current literature regarding the anticancer effects of stilbene compounds that are mediated by the targeting of telomerase and cell senescence. Finally, we provide future perspectives on the clinical utilization of stilbene compounds, especially resveratrol and pterostilbene, as novel cancer therapeutic remedies. We conclude and propose that stilbene compounds may induce senescence and may potentially be used as the therapeutic or adjuvant agents for cancers with high telomerase activity.

Unearthing the Potential Therapeutic Effects of Oxyresveratrol Based on Intrinsic Links between Pharmacological Effects: Implications for the Gut-Liver-Brain Axis.

Oxyresveratrol is a stilbene compound with a simple chemical structure and various therapeutic potentials. This study summarized and analyzed the multiple pharmacological effects and mechanisms of oxyresveratrol, identifying its prominent performance in neuroprotection, hepatoprotection, and anti-inflammatory activities in the intestines. By integrating the pharmacological effects of oxyresveratrol with insights from the network pharmacology and molecular docking of its interactions with targets linked to gut-liver-brain axis disorders, it has been shown that oxyresveratrol may hold promise for the treatment of gut-liver-brain axis-related disorders. The synergistic effect between various mechanisms has inspired further research and the development of oxyresveratrol's application value.

Assessment of the Antibacterial Mechanism of Pterostilbene against Bacillus cereus through Apoptosis-like Cell Death and Evaluation of Its Beneficial Effects on the Gut Microbiota.

Foods contaminated by harmful substances such as bacteria and viruses have caused more than 200 kinds of diseases, ranging from diarrhea to cancer. Among them, Bacillus cereus (B. cereus) is a foodborne pathogen that commonly contaminates raw meat, fresh vegetables, rice, and uncooked food. The current chemical preservatives may have adverse effects on food and even human health. Therefore, natural antibacterial agents are sought after as alternative preservatives. Stilbene compounds, including pterostilbene (PT), pinostilbene (PS), and piceatannol (PIC), which have many health benefits and exhibit antibacterial activity, were tested against B. cereus. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of PT, PS, and PIC against B. cereus ranged from 25 to 100 µg/mL. From the time-kill curve assay, PT reduced B. cereus cell survival, increased intracellular reactive oxygen species (ROS), and induced apoptosis-like cell death (ALD) in a dose-dependent manner. The quantitative real-time polymerase chain reaction (qPCR) results confirmed that treatment with PT induced genetic changes related to ALD, such as an increase in RecA gene expression and a decrease in LexA gene expression. In addition, PT showed a beneficial effect on the gut microbiota that increased the abundance of Bacteroidetes and lowered the abundance of Firmicutes. Taken together, our results showed that PT has antibacterial effects against B. cereus via ALD and is beneficial for promoting healthy gut microbiota that is worthy for the development of antibacterial agents for the food industry.

Targeting AKT/mTOR and Bcl-2 for Autophagic and Apoptosis Cell Death in Lung Cancer: Novel Activity of a Polyphenol Compound.

Autophagic cell death (ACD) is an alternative death mechanism in resistant malignant cancer cells. In this study, we demonstrated how polyphenol stilbene compound PE5 exhibits potent ACD-promoting activity in lung cancer cells that may offer an opportunity for novel cancer treatment. Cell death caused by PE5 was found to be concomitant with dramatic autophagy induction, as indicated by acidic vesicle staining, autophagosome, and the LC3 conversion. We further confirmed that the main death induction caused by PE5 was via ACD, since the co-treatment with an autophagy inhibitor could reverse PE5-mediated cell death. Furthermore, the defined mechanism of action and upstream regulatory signals were identified using proteomic analysis. Time-dependent proteomic analysis showed that PE5 affected 2142 and 1996 proteins after 12 and 24 h of treatment, respectively. The crosstalk network comprising 128 proteins that control apoptosis and 25 proteins involved in autophagy was identified. Protein-protein interaction analysis further indicated that the induction of ACD was via AKT/mTOR and Bcl-2 suppression. Western blot analysis confirmed that the active forms of AKT, mTOR, and Bcl-2 were decreased in PE5-treated cells. Taken together, we demonstrated the novel mechanism of PE5 in shifting autophagy toward cell death induction by targeting AKT/mTOR and Bcl-2 suppression.

Exploring Antiparasitic Molecule Sources from Timber by-Product Industries-Leishmanicidal and Trypanocidal Compounds from Clathrotropis brunnea Amshoff.

Through bioguided in vitro assays, the leishmanicidal and trypanocidal effects of an ethanol extract, seven fractions, and two pure substances obtained from Clathrotropis brunnea Amshoff sawdust were established. The effectiveness of the two metabolites was confirmed in a hamster model of cutaneous Leishmaniasis by Leishmania braziliensis and in Balb/c mice infected by Trypanosoma cruzi. In vitro, 3,5-dimethoxystilbene was the most active against L. braziliensis amastigotes, with a median lethal concentration (LC50) of 4.18 µg/ml (17.40 µM) and a selectivity index of 3.55, but showed moderate activity for T. cruzi, with a median effective concentration (EC50) value of 27.7 µg/ml (115.36 µM). Flavanone pinostrobin, meanwhile, showed high activity against L. braziliensis, with an EC50 of 13.61 µg/ml (50.39 µM), as well as for T. cruzi, with an EC50 of 18.2 µg/ml (67.38 µM). The animal model assay of cutaneous Leishmaniasis showed that 50% of the hamsters treated with pinostrobin were definitively cured the cutaneous ulcer, and 40% showed an improvement, with a reduction in the size of the of 84-87%. Moreover, Balb/c mice experimentally infected with T. cruzi and treated for 25 days with pinostrobin experienced a reduction in their parasitemia by 71%. These results demonstrate the high potential of C. brunnea Amshoff against cutaneous Leishmaniasis and American trypanosomiasis and indicate the pharmacological potential of waste from the wood industry, which has tons of potentially useful chemicals for the development of new medicines.

Substituent effects on the ultraviolet absorption properties of stilbene compounds-Models for molecular cores of absorbents.

The effects of substituent X and Y on ultraviolet (UV) absorption properties of stilbene compounds XPhCHCHPhY (XSBY) were studied both experimentally and computationally from the viewpoint of UV maximum absorption wavelength (λmax) and the corresponding energy (υmax). In the studies, the contribution of substituents on υmax shift was explored. The results show that with increase of electron withdrawing or electron donating ability of X or Y, there is an enhanced electron delocalization of XSBY that leads to bathochromic shift. Computational analyses based on density functional theory were conducted to elucidate the phenomena. It is disclosed that the υmax values are significantly affected by the excited state, though the electronic effect of ground state cannot be ignored. Finally, on the basis of the respective influences of X and Y, a quantitative model, which was proved reliable by the leave-one-out method, was developed to scale the effects of terminal substituents on υmax. According to the model, the effects of substituents X or Y exhibit almost the same action on υmax owing to the symmetric skeleton of the XSBY compounds. The findings provide deep insight into the effects of terminal substituents on UV absorption properties of stilbene compounds, and the derived model enables practical expression of the relationship between substituents and UV absorption.

Changes in stilbene composition during postharvest ozone treatment of 'Moscato bianco' winegrapes.

Stilbenes, including trans-resveratrol and its derivatives, are compounds naturally present in grapes and have gained a growing interest due to reported health-promoting properties. The production of resveratrol-enriched table grapes has promoted recent research on stress-induced synthesis of stilbenes. The oxidizing properties of ozone have been successfully exploited to its use as sanitizing agent and stilbene elicitor during table grapes storage. In winegrapes, this study represents the first research focused on the effect of postharvest ozone treatments on the accumulation of stilbene compounds. The study was carried out on Moscato bianco winegrapes (Vitis vinifera L.) and several gaseous ozone treatments were investigated differing in ozone dose (30 and 60 µL/L), exposure time (24 h, 48 h, and several days until 30% of weight loss), and delay time until processing (just after and several days after treatment). The stilbene production induced by ozone exposure was assessed in fresh and partially dehydrated winegrapes up to 5, 10, 15, 20, and 30% of weight loss aiming to evaluate the single and combined effect of oxidative and osmotic stresses. The results obtained showed that short-term exposure of fresh winegrapes at 60 µL/L of ozone for 48 h was not effective in inducing resveratrol accumulation just after treatment, but it had an elicitor effect on total stilbenes (+36%) in grapes subsequently dehydrated up to 20% of weight loss with a significant overproduction of trans-resveratrol and trans-piaceatannol. In addition, long-term and continuous treatments under ozone-enriched atmosphere can be also used during dehydration to sanitize winegrapes without affecting negatively the concentration of stilbenes. Therefore, the use of gaseous ozone during storage and dehydration could be indicated to reduce the use of sulfur dioxide and, depending on ozone dose and exposure time, the synthesis of stilbene compounds could increase.

The effect of light, phenylalanine and methyl jasmonate, alone or in combination, on growth and secondary metabolism in cell suspension cultures of Vitis vinifera.

The cultivated grapevine V. vinifera is a rich source of stilbene compounds such as resveratrol, which are widely believed to provide dietary protection against the development of cardiovascular disease and some forms of cancer. Elicitation is a well-known strategy to increase commercial production of natural products in plant cell suspension culture systems. Callus tissues obtained from berry slices of V. vinifera cv. Shahani grown on an optimized medium were used to develop cell suspension cultures used to study the effects of elicitation on stilbene synthesis. The effect of two light regimes (135.1 µmol. s-1 m-2 radiation, and dark), the concentration of phenylalanine (Phe; 0, 0.1, 0.5 and 1 mM) and of methyl jasmonate elicitor (MeJA; 0 and 25 µM), alone or in combination, were tested. The results showed that cultures grown in darkness resulted in significantly higher levels of the accumulation of total stilbenes (resveratrol + piceid) compared with the high light condition. The combined treatments of dark +1 mM Phe and dark +25 µM MeJA induced the synthesis of high levels of total phenolics, total flavonoids and total stilbenes. Finally, the combined elicitation of dark +1 mM Phe + 25 µM MeJA gave the highest synergistic coefficient (1.24) and proved to be the most effective treatment for the production of total phenolics, total flavonoids, and total stilbenes with mean contents of 384.80 mg GA/g DW, 527.62 mg catechin/g DW and 188.34 µg/g DW, respectively. The results of our study suggest that the combinations of dark together with MeJA and/or Phe can be used as an efficient method for the future scale-up of V. vinifera cell cultures for the production of high value stilbene compounds in a bioreactor system.

Effects of stilbenes on glucose and lipid metabolism in insulin resistant HepG2 cells / 中国药理学通报

Aim To explore the effect of four stilbenes including rhaponticin, desoxyrhaponticin, rhapontigenin and resveratrol on glucose and lipid metabolism in insulin-resistant HepG2 cells induced by high glucose and high fat. Methods The model of insulin resistance was established by incubating HepG2 cells with a complex of glucose and oleic acid. MTT assay was used to detect cell viability. The intracellular triglyceride (TG) and glucose levels were measured by the kit method. The lipid production was observed by oil red O staining, and the cell morphology and uptake of 2-NBDG were observed by confocal microscope. The PPAR signaling pathway and PI3K/Akt insulin signaling pathway related proteins were determined by Western blot to evaluate the effect of stilbenes on glycolipid metabolism in IR-HepG2 cells. Results The complex containing 50 mmol • L

Grapevine Grafting: Scion Transcript Profiling and Defense-Related Metabolites Induced by Rootstocks.

Rootstocks are among the main factors that influence grape development as well as fruit and wine composition. In this work, rootstock/scion interactions were studied using transcriptomic and metabolic approaches on leaves of the "Gaglioppo" variety, grafted onto 13 different rootstocks growing in the same vineyard. The whole leaf transcriptome of "Gaglioppo" grafted onto five selected rootstocks showed high variability in gene expression. In particular, significant modulation of transcripts linked to primary and secondary metabolism was observed. Interestingly, genes and metabolites involved in defense responses (e.g., stilbenes and defense genes) were strongly activated particularly in the GAG-41B combination, characterized in addition by the down-regulation of abscisic acid (ABA) metabolism. On the contrary, the leaves of "Gaglioppo" grafted onto 1103 Paulsen showed an opposite regulations of those transcripts and metabolites, together with the greater sensitivity to downy mildew in a preliminary in vitro assay. This study carried out an extensive transcriptomic analysis of rootstock effects on scion leaves, helping to unravel this complex interaction, and suggesting an interesting correlation among constitutive stilbenes, ABA compound, and disease susceptibility to a fungal pathogen.

A balanced JA/ABA status may correlate with adaptation to osmotic stress in Vitis cells.

Water-related stress is considered a major type of plant stress. Osmotic stress, in particular, represents the common part of all water-related stresses. Therefore, plants have evolved different adaptive mechanisms to cope with osmotic-related disturbances. In the current work, two grapevine cell lines that differ in their osmotic adaptability, Vitis rupestris and Vitis riparia, were investigated under mannitol-induced osmotic stress. To dissect signals that lead to adaptability from those related to sensitivity, osmotic-triggered responses with respect to jasmonic acid (JA) and its active form JA-Ile, abscisic acid (ABA), and stilbene compounds, as well as the expression of their related genes were observed. In addition, the transcript levels of the cellular homeostasis gene NHX1 were examined. The data are discussed with a hypothesis suggesting that a balance of JA and ABA status might correlate with cellular responses, either guiding cells to sensitivity or to progress toward adaptation.