Search Results (117)

Passiflora edulis (passion fruit) seed waste, an abundant by-product of the juice industry, is a promising source of piceatannol (PIC), a hydroxystilbene with superior antioxidant activity compared to resveratrol. However, its translation into a skin-targeted ingredient remains hindered by a lack of standardization and clinical validation. This review synthesizes current evidence on the dermatological potential of PIC and proposes a translational roadmap within a circular bioeconomy framework. Preclinical studies demonstrate that PIC exerts multi-target effects relevant to skin aging and acne, including ROS scavenging, anti-inflammatory activity via NF-κB/MAPK inhibition, suppression of melanogenesis, enhancement of hyaluronic acid and collagen synthesis, and antibacterial action against Cutibacterium acnes. However, clinical data are limited and methodologically inconsistent. To bridge this translational gap, we propose a development strategy focused on: (i) extract standardization with a proposed minimum PIC content (e.g., ≥0.3% w/w); (ii) an integrated biorefinery approach for the co-production of seed oil and phenolic fractions; and (iii) a phase-gate pipeline encompassing dermal safety assessment, advanced delivery optimization, and biomarker-correlated clinical trials. Full article

Methotrexate (MTX) is a widely used chemotherapeutic and immunosuppressive agent, but its clinical utility is limited by oxidative stress-mediated renal toxicity. This study evaluated the nephroprotective potential of the dietary polyphenolic bioactive molecule piceatannol (PIC) in its crude and liposomal nanoparticle (PIC-LNP) forms against MTX-induced kidney injury in rats. Sixty rats were allocated into six groups and received vehicle, PIC, PIC-LNPs, MTX, or combinations of MTX with PIC or PIC-LNPs. MTX administration induced marked renal dysfunction and oxidative/nitrosative stress, reflected by elevated serum urea, creatinine, and uric acid, together with increased renal ROS, MDA, protein carbonyls, 8-OHdG, and nitric oxide, in parallel with suppression of the Nrf2/HO-1 antioxidant pathway. These disturbances were accompanied by activation of TLR4/NF-κB and MAPK signaling, upregulation of pro-inflammatory cytokines, and a shift toward apoptosis, as evidenced by increased Bax and caspase-3 and reduced Bcl-2 expression. Histological and ultrastructural analyses confirmed extensive glomerular and tubular damage with mitochondrial disruption and cytoplasmic vacuolations. PIC treatment attenuated these MTX-induced alterations, whereas the liposomal formulation conferred superior protection. PIC-LNPs restored Nrf2/HO-1 signaling, enhanced endogenous antioxidant defenses, reduced oxidative/nitrosative and inflammatory responses, and normalized apoptotic markers, accompanied by substantial preservation of renal architecture and cellular integrity. Immunohistochemistry demonstrated strong Nrf2 expression with minimal NF-κB activation in the PIC-LNP group. Collectively, these findings highlight liposomal piceatannol as a promising bioactive-molecule-based strategy for controlling oxidative stress and mitigating chemotherapy-associated oxidative-stress-related renal injury. Full article

Stilbenoids are plant-derived chemical compounds that are classified as phytoalexins; recent focus has been drawn, especially on astringin, piceid, piceatannol, pterostilbene, pinosylvin, and resveratrol. These substances have been extensively studied for a variety of beneficial properties, including their effects on pathogenic microorganisms, parasites, and viruses. In their antifungal capacity, they are effective against Aspergillus spp., Botrytis spp., Candida spp., Trichophyton spp., and other fungi; tested stilbenoids have exhibited fungicidal and fungistatic effects, and inhibition of biofilm formation. Against parasites, they are effective against Echinococcus spp., Leishmania spp., Schistosoma spp., Trypanosoma spp., Toxoplasma spp., among others. Relevant action mechanisms include a reduction in parasitic enzymatic activity and inhibition of proliferation. They are also effective against different DNA and RNA viruses; the relevant mechanisms comprise reduction in viral replication, inhibition of viral genome expression, and viral attachment to cells. The toxicity of stilbenoids has been reviewed in recent papers, and, in most cases, the effective concentrations applied are well below the toxicity limit. Full article

Herein, we will review the function of the NLRP3 inflammasome in hearing loss (HL), summarize the most significant experimental results described in recent years, describe the biological mechanisms involved in the role of NLRP3 inflammasome in HL, and highlight some of the most promising small NLRP3 inhibitors for its clinical therapy, showing excellent pharmacological effects and good pharmacodynamic/pharmacokinetic profiles. Full article

Background/Objectives: Natural products containing hydroxyanthracene derivatives (HADs) such as Cascara (Rhamnus purshiana), Frangula (Rhamnus frangula), Rhubarb (Rheum palmatum), and Senna (Cassia angustifolia) have long been used for their laxative properties, but also raise safety concerns due to reported genotoxic and carcinogenic potential. Most studies have focused on quantifying HADs, whereas the broader secondary metabolite landscape of these herbal drugs remains underexplored. We aimed to generate an untargeted metabolomic fingerprint of these four species and to explore their chemical diversity using AI-based structural classification. Methods: Four commercial botanical raw materials were extracted with 60% methanol and analysed by UPLC–HRMS/MS in positive and negative ion modes. Features were processed in Compound Discoverer and annotated by accurate mass and MS/MS matching against spectral databases, then assigned to structural classes using a graph neural network classifier. Multivariate analyses (PCA, HCA) were used to compare metabolic patterns across species. Results: In total, 93, 83, 83 and 51 metabolites were annotated in cascara, frangula, rhubarb, and senna, respectively, spanning flavonoids, anthraquinones, phenylpropanoids and other classes. Only four flavonoids were shared by all species, indicating marked biochemical divergence. Several putatively species-enriched features were observed, including pavine in cascara and frangula, vicenin-2 in senna, and piceatannol in rhubarb. Senna displayed the most distinct metabolic profile, whereas cascara and frangula clustered closely. Conclusions: This work provides a chemistry-centred metabolomic fingerprint of four HAD-containing herbal drugs using graph-based neural networks for natural product classification, supporting future studies on the pharmacological potential, bioavailability and safety of their metabolites. Full article

Background: currently, there is a growing trend toward multifunctional cosmetics, which combine several active ingredients in a single product to enhance efficacy and user convenience. As ingredients may influence one another, it is important to study the behavior of mixing multiple compounds in complex formulations, especially regarding their interaction with the skin. Piceatannol, for instance, is a naturally occurring stilbene recognized for its in vitro potent antioxidant, anti-inflammatory, and anti-aging activities, making it a promising candidate for dermocosmetic use in suncare. But despite its beneficial biological activities, its cutaneous permeation remains poorly understood, particularly when delivered from complex formulations containing multiple ingredients. Objectives: in this sense, this study aimed to evaluate the in vitro skin diffusion profile of piceatannol from a passion fruit seed extract (P_ext) incorporated into a topical base (B_em) or an organic sunscreen emulsion (O_em), with or without a spilanthol-rich Acmella oleracea extract (J_ext) used as a natural permeation enhancer. Methods: due to ethical and variability issues with human and animal skins, the Strat-M™ synthetic membrane was chosen as a standardized model for the in vitro skin permeation assays. Piceatannol localization within membrane layers was examined by confocal Raman microscopy (CRM), while compound identification in donor and receptor compartments was performed via UHPLC-DAD. Results: piceatannol from B_em was detected up to 140 µm from the Strat-M™ surface and exceeded 180 µm in depth when J_ext and organic sunscreens were included in the formulation. Notably, formulations containing J_ext and those based on O_em promoted enhanced accumulation in both the stratum corneum and deeper skin layers, suggesting an improved delivery potential in lipid-rich vehicles. Conclusions: even though some instability issues were observed, piceatannol penetration into Strat-M™ from the proposed formulations was confirmed, and the results provide a foundation for further research on its topical delivery, supporting the rational development of formulations capable of harnessing its demonstrated biological properties. Full article

Chemotherapy-induced senescence (CIS) contributes to tumor persistence and relapse. In this study, we investigated the senolytic activity of piceatannol (PCT) in 5-fluorouracil (5FU)-induced senescent colorectal cancer (CRC) cells. Senescence was established in P53-proficient HCT116 cells and normal colon fibroblasts (CCD18Co) following prolonged 5FU exposure, as shown by increased SA-β-gal activity, upregulation of P16, P21, and P53, mitochondrial depolarization, and enhanced oxidative stress. Subsequent PCT treatment selectively induced apoptosis in senescent populations, while non-senescent or p53-mutant, senescence-resistant HT29 cells were minimally affected. This effect was prevented by N-acetylcysteine, indicating a redox-sensitive mechanism. Mechanistically, PCT triggered mitochondrial depolarization and AIF-associated, caspase-independent apoptosis without increasing ROS. Morphological analysis with MitoTracker and quantitative morphometry using Fiji confirmed a fragmented mitochondrial network, characterized by reduced form factor, length, and number per cell. Western blotting revealed downregulation of fusion proteins (MFN1, MFN2), decreased FIS1, stable DRP1, and marked upregulation of the DRP1 adaptor MFF, consistent with suppressed fusion and enhanced fission competence. Together, these findings demonstrate that PCT selectively targets chemotherapy-induced senescent CRC cells through mitochondrial fragmentation and AIF-dependent apoptosis, highlighting its potential as an adjuvant strategy to limit the long-term burden of therapy-induced senescence. Full article

Toxoplasma gondii, an obligate intracellular protozoan parasite infecting nucleated cells of warm-blooded vertebrates, causes severe complications in immunocompromised hosts. Current therapies remain limited by suboptimal efficacy and toxicity, necessitating novel anti-toxoplasmic agents. Piceatannol (PIC), a natural stilbenoid, demonstrates multifaceted bioactivity including antimicrobial and anti-parasitic effects, suggesting therapeutic potential against T. gondii. Our previous study revealed PIC’s potent anti-parasitic activity, selectively inhibiting T. gondii proliferation and altering parasite morphology without host cytotoxicity. In this study, mechanistic analyses indicated that PIC disrupts mitochondrial integrity in tachyzoites, reducing mitochondrial membrane potential and ATP production while elevating ROS levels. Transcriptomic profiling identified significant suppression of oxidative phosphorylation-related genes, consistent with mitochondrial dysfunction. These findings establish PIC as a promising candidate targeting T. gondii through the mechanism of mitochondrial impairment. Full article

Passion fruit (Passiflora edulis) is consumed worldwide, and its processing generates a substantial amount of waste, particularly from the seeds and peels. This study investigated the potential of valorizing passion fruit seeds by adding them to high-fiber snack bars. Seed-enriched snack bars were evaluated for their sensory qualities, antioxidant activities, and nutritional compositions. Seed addition markedly increased the dietary fiber content (from 4.17% to 5.66%), fat content (from 15.02% to 19.63%), and antioxidant activity (e.g., 83.38% vs. 82.47% DPPH inhibition at 50 ppm) compared to the control. This was mainly due to the presence of piceatannol, a potent bioactive molecule. The overall phenolic content decreased from 90.11 to 65.37 mg GAE/100 g, suggesting intricate matrix interactions. The control bars exhibited a higher overall acceptability score, whereas the seed bars remained within the acceptable sensory range and required only minor texture adjustments. Microbiological analyses confirmed that both formulations retained their safety for 7 days at +4 °C, with appropriate levels of yeast and total viable count and no mold growth. These results suggest that passion fruit seeds have the potential to be used as a sustainable functional food ingredient. Further research is warranted to improve the sensory qualities and shelf-life stability. Full article

The traditional aging of cachaça has been performed with different types of wood barrels. Although it is efficient for incorporating phenolics, volatiles, and color into the drink, it is time-consuming for the industry. Alternative aging processes, such as the use of wood chips, have been proposed, and they have the advantage of achieving aging in a shorter time and producing a quality and innovative drink. Therefore, the influence of jackfruit wood barrel and chips and micro-aeration was investigated during cachaça aging. For that, five treatments were used—stainless steel tank (control); stainless steel tank and micro-aeration (control); jackfruit wood barrel; stainless steel tank with jackfruit chips; and stainless steel tank with jackfruit chips and micro-aeration—during two aging times (40 and 79 days). Aging cachaça with jackfruit wood led to increased physicochemical, color, and total phenolic contents, whereas alcoholic degree, lightness, and copper contents decreased. No influence was observed on higher alcohols. Nineteen phenolic compounds were identified in the jackfruit wood aged cachaça by HPLC-DAD-FLD. Myricetin was predominant, a potential marker for jackfruit wood. Longer aging time decreased the alcoholic degree and total ester, but it increased dry extract, density, total and volatile acidity, and it improved the quality of cachaça. The use of chips accelerated aging, whereas micro-aeration led to decreased myricetin. PCA and HCA clustered the samples into three groups: the first was correlated with several flavonoids and coumarins; the second with myricetin, piceatannol, and trans-ferulic acid; and the last with ellagic acid. The use of jackfruit chips in the aging of cachaça has been shown to be a promising innovation. Full article

Background/Objectives: Periodontal disease involves chronic immunoinflammatory processes and microbial dysbiosis, making phytochemicals with anti-inflammatory properties potential therapeutic agents. This study aimed to assess the modulatory effects of yellow passion fruit bagasse extract (PFBE) on periodontal cells under microbial condition. Methods: A human periodontal ligament (PDL) cell line was exposed to F. nucleatum ATCC 25586 to simulate a microbial environment in vitro in the presence and absence of PFBE containing three different concentrations (0.25, 0.50, and 1.00 µg/mL) of piceatannol. Pro-inflammatory markers (TNF-α, IL-8, CCL2), the antioxidant enzyme SOD2, and the protease marker MMP-1 were analyzed by real-time PCR. Protein levels were assessed via ELISA and NF-κB nuclear translocation by immunofluorescence. Cell viability was investigated using live/dead and alamarBlue assays, and in vitro wound healing was evaluated by an automated scratch assay. Results: PDL cells exposed to F. nucleatum significantly increased the gene and protein expression of all inflammatory markers. The stimulatory effects of F. nucleatum were significantly reduced when PDL cells were simultaneously exposed to PFBE. F. nucleatum triggered the NF-κB nuclear translocation while PFBE abrogated the F. nucleatum-stimulated NF-κB nuclear translocation at 60 min. Viability assays demonstrated that neither PFBE nor F. nucleatum were toxic or significantly affected PDL cell viability. In vitro wound closure was improved by the addition of PFBE to F. nucleatum. Conclusions: PFBE exhibited anti-inflammatory and anti-proteolytic effects while improving in vitro wound healing, suggesting a potential modulatory role of PFBE in periodontal disease prevention and treatment. Full article

Rheumatoid arthritis (RA) is a highly prevalent systemic autoimmune disease. Recently, natural small molecules have been explored as alternative therapeutic agents. Iris halophila Pall is the traditional herbal medicine, and it is rich in active ingredients with anti-inflammatory and immunomodulatory effects. In our previous study, LC-MS analysis revealed that piceatannol (PIC) is one of the primary active ingredients in the root of Iris tectorum. The purpose of this study was to explore the immunomodulatory effects of PIC on the maturation and function of dendritic cells, as well as on experimental arthritis induced by complete Freund’s adjuvant (CFA) and incomplete Freund’s adjuvant (IFA). Additionally, we aimed to probe into the potential mechanisms underlying the effects of PIC. We first verified the immunosuppressive effect of PIC using flow cytometry and an ELISA. The immunosuppressive mechanism of PIC on dendritic cells (DCs) was investigated through a joint analysis of network pharmacology and Western blotting. Our findings revealed that under Lipopolysaccharide (LPS)-induced inflammatory conditions, PIC could restrain the maturation and function of DCs (p < 0.001) and decrease the secretion of inflammatory cytokines (p < 0.001) compared to the LPS group. Furthermore, PIC suppressed the activation and polarization of CD4⁺ T cells, resulting in a decreased proportion of Th1 and Th17 cells (p < 0.001), ultimately improving the symptoms of CFA-induced arthritis in comparison to the model group. The PIC-induced shift in the T helper cell differentiation correlated with the secretion of polarizing cytokines from DCs in the AIA model. Mechanistically, PIC exerted its immunosuppressive function mainly by down-regulating the Mitogen-Activated Protein Kinase (MAPK) and Nuclear Factor kappa-B (NF-κB) signaling pathways. Collectively, these data unveil the anti-inflammatory mechanisms of a traditional medicine via the inhibition of the immune activation function of DCs in vivo and open up a therapeutic approach for autoinflammatory diseases. Full article

Plant-based stilbenes are low-molecular-weight polyphenolic compounds that exhibit anti-oxidant, anti-microbial, anti-fungal, anti-inflammatory, anti-diabetic, cardioprotective, neuroprotective, and anti-cancer activities. They are phytoalexins produced in diverse plant species in response to stress, such as fungal and bacterial infections or excessive UV irradiation. Plant-derived dietary products containing stilbenes are common components of the human diet. Stilbenes appear to be promising chemopreventive and chemotherapeutic agents. Accumulating evidence indicates that stilbenes are able to trigger both apoptotic and autophagic molecular pathways in many human cancer cell lines. Of note, the molecular crosstalk between autophagy and apoptosis under cellular stress conditions determines the cell fate. The autophagy and apoptosis relationship is complex and depends on the cellular context, e.g., cell type and cellular stress level. Apoptosis is a type of regulated cell death, whereas autophagy may act as a pro-survival or pro-death mechanism depending on the context. The interplay between autophagy and apoptosis may have an important impact on chemotherapy efficiency. This review focuses on the in vitro effects of stilbenes in different human cancer cell lines concerning the interplay between autophagy and apoptosis. Full article

The interest in new sources of bioactive compounds has been driven by the search for natural antioxidants capable of attenuating the toxicity of reactive oxygen species, as well as the emergence of pathogens resistant to antimicrobials. In this sense, we explored the potential of the macaúba epicarp. Compounds such as piceatannol, 3,4,5,3′,5′-penta-hydroxy-trans-stilbene (PHS), and in lower amounts, resveratrol were identified in extracts through techniques such as medium-pressure liquid chromatography, HPLC-MS, and imaging mass spectrometry (IMS), which confirmed the exclusive localization of PHS and piceatannol in the outer epicarp. Extraction with aqueous acetone (Me₂CO:H₂O) and its EtOAC fraction showed the highest yields of stilbenes and, moreover, it efficiently increased the tolerance of Saccharomyces cerevisiae to oxidative stress. Additionally, the Me₂CO:H₂O extract presented antibacterial and anti-cryptococcal activity, with piceatannol and resveratrol increasing survival rates of Galleria mellonella subjected to fungal infection. In silico ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis indicates low toxicity for piceatannol, PHS, and resveratrol, in addition to pharmacokinetic parameters that allow their use. These findings indicate the use of macaúba epicarp as a source of bioactive compounds valuable for the food, cosmetic, and pharmaceutical industries. Full article

Stilbenoids are a class of naturally occurring phenolic compounds found in various plant species, characterized by a stilbene backbone with diverse substituents that confer a range of biological activities. These compounds exhibit antioxidant, anti-inflammatory, and antimicrobial properties, making them promising candidates for improving intestinal health. The intestinal tract plays a critical role in nutrient digestion, absorption, and immune defense, and maintaining its integrity is vital for animal growth. Stilbenoids contribute to gut health by enhancing intestinal morphology, supporting mucosal immune responses, regulating gut microbiota composition, modulating metabolic pathways, and maintaining mitochondrial health. This review provides a comprehensive analysis of key stilbenoids, including resveratrol, pterostilbene, piceatannol, and oxyresveratrol, focusing on their biological effects and regulatory mechanisms. By highlighting their roles in mitigating intestinal inflammation and promoting gut function, this review provides a basis for the practical application of stilbenoids in animal health and husbandry. Full article