Search Results (88)

M. crystallinum is an edible halophytic succulent plant rich in phenolic compounds with potential pharmaceutical applications. However, it is known that these phytocompounds generally present low absorption, which hinders their direct use in formulations. Therefore, delivery systems, such as phytosomes, can be regarded as a potential strategy to overcome this disadvantage. This study aimed, for the first time, to prepare extracts from the ice plant using different solvents and to incorporate them into phytosomes. Physicochemical characterization of these phytosomes, their antioxidant activity, as well as the quantification and in vitro release profile of their phenolic and flavonoid compounds were studied. Different extraction solvents were assayed, and Ethanol:Acetone (80:20) achieved a strong antioxidant activity (reaching ca. 71.16%), extracting 3200.3 mg of GAE/100 g and 761.7 mg of QE/100 g of phenolic and flavonoid compounds, respectively. The phytosomal formulation exhibited a mean particle size of 233.80 nm, a polydispersity index of 0.23, and a zeta potential of −27.27 mV. Furthermore, a high encapsulation efficiency (96.63%) of the extracts in the phytosomes was obtained. The in vitro release test indicated that the antioxidant activity was retained, reaching a maximum of 42%, accompanied by a release of 51% of the flavonoid content at the end of the 3 h assay, under the experimental conditions. These findings highlight the potential of phytosomes formulated with Mesembryanthemum crystallinum extract as a delivery system for antioxidant phytochemicals. Full article

Background/Objectives: The flavonoid quercetin (Q) has recently been suggested as a natural anti-aging and senolytic agent. However, its low stability and poor oral bioavailability may limit its efficacy. To address this, we investigated whether a lecithin-based formulation of Q, Quercefit™ (QF), enhances stress resistance and delays aging in vivo. Methods: The nematode Caenorhabditis elegans was used as an animal model to evaluate the effects of QF under physiological and stress conditions. Unformulated Q was administered as a control. Worm survival, healthspan, resistance to thermal and oxidative stress, and expression of stress- and longevity-related genes were assessed. All the experiments were conducted at least in triplicate, each including a minimum of 15 worms. The data were analyzed using Student’s t-test, one-way or two-way ANOVA, and Bonferroni’s post hoc test. Results: One hundred micromolar Q administered in QF was more effective than equimolar unformulated Q in increasing the worms’ ability to resist acute thermal stress at 35 °C (tested on 75 worms/group) and oxidative stress caused by 0.5 mM hydrogen peroxide (tested on 75 worms/group). In this last case, the protective effect of QF was similar to that of N-acetylcysteine and ascorbic acid. Under experimental conditions mimicking the long-term consequences of thermal stress, QF, like Q, increased the worms’ lifespan and healthspan by approximately 50%, counteracting the age-related decline associated with stress (120 worms/group). These benefits are supported by QF’s capacity to act as a reactive oxygen species scavenger; suppress heat-shock element gene transcription activated by thermal stress, such as hsp-16.2 and hsp-70, and stimulate the sod-3 and gst-4 genes that are involved in antioxidant and detoxification responses. Conclusions: These findings suggest that Q, when administered in the QF formulation, can act at the transcriptional level to protect against aging induced by stressful conditions. Full article

Plant-based biomaterials are increasingly recognized as bio-instructive platforms capable of actively modulating immune responses rather than functioning solely as passive structural supports. In this context, the term plant-based refers to photosynthetic biomass-derived platforms, including both terrestrial plants and marine macroalgae, reflecting their shared richness in polysaccharides and secondary metabolites relevant to immune engineering and regenerative medicine. This review critically synthesizes current evidence on plant-derived polysaccharides and phytochemicals, including algal sulfated polysaccharides (fucoidan, alginate, carrageenan, and ulvan), terrestrial plant polysaccharides (e.g., Lycium barbarum and Aloe vera derivatives), polyphenols, and other secondary metabolites such as terpenoids and alkaloids, highlighting their roles as immunomodulators in biomedical contexts. Key mechanisms include macrophage polarization along an M1–M2 continuum, pattern recognition receptor engagement, redox and metabolic regulation, and crosstalk between innate and adaptive immunity, with emphasis on context-dependent signaling and structural heterogeneity. Material design parameters, including molecular weight and chemical functionalization, are critical determinants of immune responses. Advanced delivery systems, such as hydrogels, nanocomposites, phytosomes, and plant-derived extracellular vesicles (EVs), enable improved stability and spatiotemporal control. Applications in wound and musculoskeletal regeneration are discussed alongside translational challenges, including variability, reproducibility, regulatory issues, and the need for standardized characterization and immune validation. Full article

Terpenoids represent a large class of bioactive natural compounds with promising pharmacological properties, including anti-inflammatory, antimicrobial, and anticancer activities. However, their clinical application is often limited by poor aqueous solubility, low membrane permeability, and suboptimal bioavailability. Phytosomal delivery systems have emerged as a promising strategy to enhance the pharmacokinetic performance of plant-derived compounds by forming molecular complexes between bioactive molecules and phospholipids. This review critically examines the structural principles, preparation methods, physicochemical characterization, and biological performance of terpenoid phytosomes. Particular attention is given to the molecular interactions between terpenoids and phospholipids that govern complex formation and vesicular assembly. The review also summarizes current analytical techniques used to confirm phytosome formation and discusses the influence of formulation parameters, including phospholipid composition and molar ratios, on stability and biological activity. In addition, emerging insights from molecular modeling and membrane interaction studies are considered to better understand the mechanisms underlying improved drug delivery. Finally, challenges related to safety assessment, manufacturing scalability, and clinical translation of phytosomal systems are discussed. Overall, terpenoid phytosomes represent a promising nanodelivery platform capable of improving the pharmacokinetic profile and therapeutic potential of terpenoid compounds. Full article

Plant-derived extracellular vesicles (PDEVs), engineered phytosomes, bioinspired polymeric plant-based nanoparticles (PBNPs), hybrid phyto-inorganic nanocomposites, green-synthesized metal nanoparticles, self-assembled nanoarchitectures, and multifunctional composites represent a rapidly advancing class of sustainable, nature-inspired nanocarriers. These platforms combine exceptional biocompatibility, negligible immunogenicity, and renewable sourcing with tunable drug loading, targeted delivery, and controlled release properties. This review synthesizes translational advances from 2020 to 2026, covering scalable isolation/bioprocessing (bioreactors, elicitation), multi-parametric physicochemical/multi-omics characterization, rational engineering/hybridization, and rigorous in vitro/in vivo assessments of uptake, biodistribution, pharmacokinetic (PK), and efficacy. Phytosomes and PBNPs markedly enhance oral bioavailability and targeted delivery of lipophilic phytochemicals, while PDEVs offer unique immunomodulatory, anti-inflammatory, and gene-regulatory activities. Hybrid and green-synthesized systems provide structural stability, redox modulation, and synergistic effects, and self-assembled/multifunctional composites address solubilization barriers with stimuli-responsive design. Early-phase human studies on grapefruit-, ginger-, turmeric-, and ginseng-derived PDEVs report excellent short-term safety, favorable PK, and preliminary bioactivity signals, with no observed immunogenicity or dose-limiting toxicities; however, these trials remain exploratory, constrained by small sample sizes and safety-focused endpoints. Despite challenges, including methodological heterogeneity, variable yields, long-term safety uncertainties (notably for inorganic hybrids), and regulatory ambiguities, emerging strategies such as clustered regularly interspaced short palindromic repeats (CRISPR)-engineered plant line; artificial-intelligence-driven process optimization; standardized guidelines, and integrated clinical, intellectual property, and commercialization frameworks are progressively addressing these barriers. Collectively, these advances position plant-derived nanocarriers as immunologically privileged, eco-friendly alternatives to synthetic and mammalian platforms, laying the foundation for a sustainable era of precision phytomedicine. Full article

Background: Chronic neuropathic low back pain (LBP) is a prevalent health condition and difficult to treat. Conventional therapies often provide limited relief and raise safety concerns. Supplemental palmitoylethanolamide (PEA), an endogenous fatty acid amide with analgesic and anti-inflammatory properties, has shown benefits in neuropathic pain, but its application as a supportive strategy has been limited by poor oral bioavailability. Objectives: This study aimed to investigate a phospholipid-based palmitoylethanolamide formulation (PEA-PL, Cronilief™), developed using Phytosome™ delivery technology, with respect to solubility optimization, systemic exposure, and associated clinical effects in individuals with chronic neuropathic LBP. Methods: PEA-PL solubility was assessed in fasted-state simulated intestinal fluid and compared with unformulated PEA. Plasma PEA concentrations were evaluated in healthy volunteers after 2 weeks of supplementation with unformulated PEA (300 mg/day) or PEA-PL (300 or 600 mg/day). Clinical efficacy was assessed in a double-blind, placebo-controlled randomized, trial in which 120 adults with neuropathic LBP received PEA-PL 600 → 300 mg (n = 40), PEA-PL 450 mg (n = 40), or placebo (n = 40), daily for 8 weeks in addition to Standard of Care. Primary outcomes were effects on neuropathic pain (Douleur Neuropathique 4, DN4) and its intensity (Numeric Pain Rating Scale, NPRS). Secondary outcomes included effect on functional disability (Oswestry Disability Index, ODI), sleep quality (Pittsburgh Sleep Quality Index, PSQI), quality of life (QoL) (SF-12), and concomitant analgesic use. Safety was monitored throughout the 8-week supplementation period. Results: PEA-PL increased PEA solubility approximately eight-fold and resulted in higher plasma PEA concentrations than unformulated PEA. Both PEA-PL regimens significantly improved pain, functional disability, sleep, and QoL outcomes versus placebo (all p < 0.0001), with greater effects for the 600 → 300 mg regimen. Analgesic discontinuation occurred more frequently in PEA-PL groups (65–70%). Supplementation was well tolerated. Conclusions: A phospholipid-based (Phytosome™) PEA formulation (Cronilief™) was developed and associated with optimized systemic exposure and clinically meaningful reductions in pain severity and functional disability in individuals with chronic neuropathic LBP. Full article

Immune dysregulation and chronic inflammation are central contributors to many diseases. Curcuma longa L. and Echinacea purpurea (L.) Moench are widely used medicinal plants with extensive preclinical evidence supporting immunomodulatory effects. Their key metabolites, curcuminoids, turmerones, alkamides, polysaccharides, and caffeic acid derivatives, engage with critical pathways, including NF-κB, MAPK, JAK/STAT, and Nrf2. This interaction modulates cytokine production, oxidative stress responses, and both innate and adaptive immune activities. Although numerous mechanistic and early clinical studies support these actions, human evidence remains inconsistent, partly due to poor and variable oral bioavailability and substantial heterogeneity in extract composition, despite the existence of some standardized preparations. Recent technological strategies, including micelles, phytosomes, phospholipid complexes, nanoemulsions, polymeric nanoparticles, and liposomal systems, have improved solubility, stability, and systemic exposure of key metabolites, particularly curcuminoids. However, clinical results are still limited and often derived from small or heterogeneous trials. This review summarizes the ethnopharmacological background, mechanistic data, clinical findings, and formulation advances for both species and highlights the translational barriers that restrict their therapeutic application. Rigorous clinical studies using standardized and technologically optimized preparations are required to determine the true immunomodulatory potential of C. longa and E. purpurea. Full article

This study, for the first time, evaluated the therapeutic potential of resveratrol-loaded phytosome nanoparticles (RES-PNPs) against Ehrlich ascites carcinoma (EAC) and associated testicular dysfunction, compared with free resveratrol (RES). Ninety male Swiss albino mice were divided into six groups, (1) control; (2) RES (10 mg/kg/day, orally); (3) RES-PNPs (10 mg/kg/day, orally); (4) EAC, induced by intraperitoneal injection of 2.5 × 10⁶ cells; (5) EAC + RES; and (6) EAC + RES-PNPs, treated for 20 days post-tumor inoculation. Tumor growth parameters, reproductive function, antioxidant enzyme activities, inflammatory mediators, apoptotic markers, and histopathological features were assessed. Additionally, in silico docking was performed to identify molecular targets mediating RES effects. RES-PNPs markedly reduced tumor volume, ascitic cell viability, and body weight gain while significantly prolonging survival compared with free RES. Molecular assays revealed enhanced pro-apoptotic signaling (increased Bax and Caspase-3, decreased Bcl-2), suppression of vascular endothelial growth factor (VEGF), and inhibition of COX-2 with reduced TNF-α, IFN-γ, and IL-1β levels. RES-PNPs also restored semen quality, normalized reproductive hormones, elevated antioxidant enzyme activities, and reduced lipid and protein oxidation, corroborated by notable testicular histological protection. In conclusion, Resveratrol-loaded phytosome nanoparticles provide superior anti-tumor, antioxidant, anti-inflammatory, and pro-apoptotic benefits compared with free RES. These findings highlight RES-PNPs as a potent and stable nanoformulation for effective EAC suppression and preservation of male reproductive integrity. Full article

Background/Objectives: Rutin (RT), a promising bioflavonoid, faces clinical limitations due to its poor solubility and bioavailability. In this study, we formulated RT-loaded phytosome nanoparticles (RT-PNPs) via thin-layer hydration and characterized their morphology, size distribution, and zeta potential. Methods: We established a mouse model of Ehrlich ascites carcinoma (EAC), randomly allocating ninety female Swiss albino mice into six groups: untreated controls, RT-treated, RT-PNP-treated, EAC, EAC + RT, and EAC + RT-PNPs. Tumor induction and treatment protocols were controlled, with the oral administration of 25 mg/kg/day of RT or RT-PNPs for 20 days. We comprehensively assessed survival, body weight, ascitic fluid/tumor volume, and cell viability and performed detailed hematological, serum biochemical, and tumor marker analyses. Multiorgan (liver and kidney) function and redox homeostasis were evaluated through enzymatic assays for SOD, CAT, GSH-Px, and GSH, as well as lipid peroxidation assessment. Proinflammatory cytokines and tumor markers (AFP, CEA, CA19-9, CA125, and CA15-3) were quantified via ELISA. Results: Gene expression profiling (TP53, Bax, and Bcl-2) and flow cytometry (p53 and Ki-67) elucidated the modulation of apoptosis. Histopathological scoring documented organ protection, while advanced multivariate (heatmap and principal component) analyses revealed distinct treatment clusterings. The RT-PNPs demonstrated potent anti-tumor, antioxidant, anti-inflammatory, and apoptosis-inducing effects, outperforming free RT in restoring physiological markers and tissue integrity. Conclusions: The current results underscore the potential of RT-PNPs as a multifaceted therapeutic approach to EAC, leveraging nanoparticle technology to optimize efficacy and systemic protection. Full article

Curcumin, a bioactive polyphenol from turmeric, faces significant challenges in food and pharmaceutical applications due to its poor water solubility, low stability, and limited bioavailability. In this study, curcumin–lecithin complexes (phytosomes) were spray-dried using maltodextrin as the carrier polymer to produce free-flowing powders with improved physicochemical properties. The powders were characterized based on moisture content, particle size, morphology, curcumin loading, thermal behavior, and stability under simulated gastrointestinal and thermal conditions. The lecithin–curcumin complexes exhibited high entrapment efficiency (up to 94%), a predominantly amorphous structure, and improved thermal and digestive stability compared to free curcumin. Particle size and wettability were influenced by carrier and curcumin ratios, with maltodextrin enhancing powder flowability and apparent solubility. Morphological analyses revealed spherical particles with core–shell structures, confirming successful complexation. The complexes protected curcumin from degradation at intestinal pH and elevated temperatures, highlighting their potential for enhanced bioavailability. These findings demonstrate that spray-dried curcumin–lecithin complexes with maltodextrin carriers offer a promising strategy to overcome curcumin’s solubility and stability limitations, supporting their application in functional foods and pharmaceuticals. Full article

Callistemon citrinus has shown antioxidant and anti-inflammatory properties in certain tissues. However, its impact on the brain remains unproven. This study investigates the effect of C. citrinus extract and phytosomes on the oxidative status of the brains of rats fed a high-fat–fructose diet (HFD). Fifty-four male Wistar rats were randomly divided into nine groups (n = 6). Groups 1, 2, and 3 received a standard chow diet; Group 2 also received the vehicle, and Group 3 was supplemented with C. citrinus extract (200 mg/kg). Groups 4, 5, 6, 7, 8, and 9 received a high-fat diet (HFD). Additionally, groups 5, 6, 7, 8, and 9 were supplemented with orlistat at 5 mg/kg, C. citrinus extract at 200 mg/kg, and phytosomes loaded with C. citrinus at doses of 50, 100, and 200 mg/kg, respectively. Administration was oral for 16 weeks. Antioxidant enzymes, biomarkers of oxidative stress, and fatty acid content in the brain were determined. A parallel artificial membrane permeability assay (PAMPA) was employed to identify compounds that can cross the intestinal and blood–brain barriers. The HFD group (group 4) increased body weight and adipose tissue, unlike the other groups. The brain fatty acid profile showed slight variations in all of the groups. On the other hand, group 4 showed a decrease in the activities of antioxidant enzymes SOD, CAT, and PON. It reduced GSH level, while increasing GPx activity as well as MDA, 4-HNE, and AOPP levels. C. citrinus extract and phytosomes restore the antioxidant enzyme activities and mitigate oxidative stress in the brain. C. citrinus modulates oxidative stress in brain tissue through 1.8-cineole and α-terpineol, which possess antioxidant and anti-inflammatory properties. Full article

Cardiovascular injury caused by fine particulate matter (PM2.5) exposure is an escalating public health concern due to its role in triggering systemic inflammation and oxidative stress. This study elucidates the sirtuin 1 (SIRT1)-mediated epigenetic mechanisms underlying the protective effects of phytosome-encapsulated Zea mays L. var. ceratina tassel extract (PZT) in a rat model of PM2.5-induced cardiovascular inflammation. Male Wistar rats were pretreated with PZT (100, 200, and 400 mg/kg body weight) for 21 days before and throughout a 27-day PM2.5 exposure period. SIRT1 expression and associated inflammatory and oxidative stress markers were evaluated in cardiac and vascular tissues. The findings revealed that PZT significantly upregulated SIRT1 expression, a key epigenetic regulator known to modulate inflammatory and antioxidant pathways. The activation of SIRT1 inhibited the nuclear factor-kappa B (NF-κB) signaling pathway, leading to a reduction in pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) within cardiac tissue. In vascular tissue, treatment with PZT reduced the levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β), thereby mitigating inflammatory and fibrotic responses. Furthermore, SIRT1 activation by PZT enhanced the antioxidant defense system by upregulating superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), which was associated with a decrease in malondialdehyde (MDA), a marker of lipid peroxidation. Collectively, these results demonstrate that PZT confers cardiovascular protection through SIRT1-dependent epigenetic modulation, mitigating PM2.5-induced inflammation, oxidative stress, and tissue remodeling. The dual anti-inflammatory and antioxidant actions of PZT via SIRT1 activation highlight its potential as a functional food-based preventative agent for reducing cardiovascular risk in polluted environments. Full article

Neurodegenerative diseases affect millions worldwide and present an urgent challenge due to the aging of the population. Drug delivery to the brain is limited by the blood–brain barrier (BBB), inspiring the development of nanotransporters like phytosomes. This study aimed to develop phosphatidylcholine (PC)-based phytosomes incorporating macroalgae extracts. Some of them were functionalized with PEG and ApoE to enhance BBB passage. The phytosomes were characterized by the encapsulation rate, size, polydispersity index (PDI), zeta potential, and stability, with BBB passage tested in an in vitro model (transwell hCMEC/D3 cell model). The phytosomes showed high stability and effective extract binding (74.9–80.3%) over four weeks. Although ApoE functionalization did not significantly improve BBB crossing, all nanotransporters successfully traversed the BBB in the model. Full article

Lipid vesicles, liposomes and phytosomes have been gaining significant attention in various applications for phytochemical preservation. Furthermore, yerba mate (Ilex paraguariensis) contains a high content of bioactive compounds with functional properties; however, its liquid extract exhibits limited stability. For the first time, lipid vesicles containing yerba mate extract were produced and characterized. They were prepared using pure or purified phosphatidylcholine (PC) and n-hexane as a solvent via the reverse phase evaporation method. Their characterization was conducted using Fourier transform infrared spectroscopy (FTIR), UV–vis spectroscopy, Zeta potential (PZ), and dynamic light scattering (DLS). The decrease or absence of FTIR bands and UV–vis absorbance (325 nm) from the yerba mate extract suggests the successful dispersion of yerba mate extract in the liposome membrane, ensuring its encapsulation or complexation. Additionally, the size of lipid vesicles decreased from 625.1 nm to 440.5 nm (pure PC) and from 690.0 nm to 518.6 nm (purified PC) after the addition of yerba mate extract PZ values showed a slight change in all vesicles enhancing colloidal stability. This, combined with the reduction observed in DLS, suggests membrane reorganization, leading to the formation of unilamellar liposomes. Our observations indicate the possible formation of phytosomes, although additional studies are necessary to confirm this mechanism. Full article

Quercetin, a natural flavonoid, present in various vegetables and fruits, has garnered increasing attraction for its potential antiallergic properties. Its broad-spectrum activity depends on its anti-inflammatory, immunomodulatory, and antioxidant effects, which target the critical pathways involved in type 2-driven allergic inflammation. Quercetin inhibits mast cell degranulation, reduces the production of histamine and pro-inflammatory cytokines, and restores homeostasis of the immune system by modulating the Th1/Th2 and Treg/Th17 balances. Additionally, its antioxidant properties help to dampen oxidative stress, a critical factor in the pathophysiology of allergic diseases. In vitro studies have consistently demonstrated quercetin’s ability to suppress allergic reactions. In contrast, in vivo studies, particularly in murine models of allergic rhinitis, have confirmed its efficacy in relieving symptoms (such as nasal itching, sneezing, rhinorrhea, and congestion) and dampening type 2 mucosal inflammation. Preclinical evidence also supports its therapeutic potential in asthma, conjunctivitis, atopic dermatitis, and food allergies. However, human studies are still scarce, as only two clinical trials investigated quercetin as a monotherapy. Both studies reported promising results, including symptom reduction and improved quality of life, though larger, randomized trials are needed to validate these findings. Some other studies have investigated multicomponent products that also contain quercetin. This review aimed to report and discuss the most recent in vitro and in vivo evidence on quercetin’s application in allergic models. It also provides a comprehensive overview of human studies, highlighting its potential as an agent in food supplements to manage patients with allergic diseases. Moreover, this review introduces a new quercetin phospholipids formulation that may represent a keystone in clinical use. The literature search was based on a PubMed consultation considering the most recent (last five years) publications using the keywords “quercetin and allergic disease” and “quercetin and immune system”. Full article