Search Results (554)

Background: Skin aging is driven by oxidative stress and ultraviolet (UV) exposure, leading to extracellular matrix degradation and loss of skin elasticity. This study aimed to identify the most biologically active Citrus species using a bioassay-guided approach and evaluate its potential for dermal applications. Methods: Hydroalcohol extracts and ethyl acetate fractions of Citrus sinensis, Citrus aurantifolia, and Citrus reticulata leaves were screened for antioxidant, enzyme-inhibitory, and polyphenol content. The most active fraction was characterized by UPLC-PDA and LC–MS/MS, formulated into Span-based nanovesicles, and evaluated for physicochemical properties and drug release. Biological activity was assessed using an in vitro scratch wound-healing assay on human dermal fibroblasts and a UVA-induced photoaging mouse model, supported by molecular dynamics simulations. Results: The ethyl acetate fraction of C. aurantifolia (CAE) exhibited the highest biological activity among the tested samples. This fraction showed potent antioxidant activity (DPPH IC₅₀ = 3.53 ± 0.05 µg/mL), marked inhibition of elastase (91.3%), collagenase (92.0%), and tyrosinase (80.2%), and a high total flavonoid content (110.49 mg rutin equivalents/g). Phytochemical profiling of CAE tentatively identified fourteen compounds, predominantly flavonoids, with hesperidin (30.4 mg/g) as a major constituent. The optimized nanovesicles (184 ± 0.9 nm, PDI 0.10, EE% 75.0%) enabled sustained hesperidin release. CAE and CAEnp enhanced fibroblast migration and accelerated wound closure at 24 h (p < 0.05). In vivo, CAEnp improved UVA-induced histopathological alterations and modulated oxidative stress-related markers by reducing p62/SQSTM1 by 28.7%, Keap1 expression to 21% compared with the CAE-treated group, and enhancing Nrf2, ARE, and NQO1 expression by 54.1%, 28.3%, and 57%, respectively. Molecular dynamics simulations supported stable hesperidin binding to elastase and suggested possible modulation of collagenase flexibility. Conclusions: The polyphenol-rich leaf fraction from C. aurantifolia, identified through comparative bioassay-guided fractionation, demonstrated antioxidant, enzyme-inhibitory, wound-healing, and photoprotective effects, particularly after nanoformulation. These findings support its potential for further development as a natural topical anti-aging candidate. Full article

This study presents an integrated evaluation of the organ-specific phenolic composition and antioxidant activity of Cicer isauricum. Extracts obtained from leaves, stems, and roots were analyzed using liquid chromatography–electrospray ionization tandem mass spectrometry (LC–ESI–MS/MS) and multiple in vitro antioxidant assays. LC–MS/MS analysis revealed a distinct organ-dependent distribution of phenolic compounds. Stem extracts were characterized by high levels of hyperoside (2227.97 µg/g extract), luteolin (298.22 µg/g), and eriodictyol (434.03 µg/g), while leaves were rich in hyperoside (1162.42 µg/g), hesperidin (459.40 µg/g) and kaempferol (182.88 µg/g). Root extracts were dominated by flavan-3-ols, particularly (+)-catechin (355.93 µg/g) and (–)-epicatechin (59.58 µg/g), indicating a differentiated metabolic profile. Antioxidant assays, including cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, demonstrated that root extracts exhibited the strongest activity, with the lowest IC₅₀ values (DPPH: 4.15 mg/mL; ABTS: 1.41 mg/mL) and highest reducing power (FRAP EC₅₀: 0.41 mg/mL; CUPRAC EC₅₀: 1.78 mg/mL). Correlation analysis confirmed strong associations between total phenolic content and antioxidant capacity, while compound-level evaluation highlighted flavan-3-ols as major contributors. These findings identify roots of C. isauricum as a promising source of natural antioxidants. Full article

Background: Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia resulting from impaired insulin secretion or action. Persistent hyperglycemia contributes to the development of micro- and macrovascular complications, particularly affecting the kidneys and leading to diabetic nephropathy through mechanisms involving oxidative stress, fibrosis and apoptosis. Purpose: This study aimed to investigate the protective effects of hesperidin and carvacrol, individually and in combination, on streptozotocin-induced diabetic nephropathy in a Type 1 diabetes rat model. Study design: An experimental in vivo animal study was conducted using a streptozotocin-induced Type 1 diabetic rat model. Methods: Sixty adult Wistar Albino rats were randomly divided into six groups (n = 10): Control, Diabetes, Vehicle, Diabetes + Carvacrol, Diabetes + Hesperidin, and Diabetes + Hesperidin + Carvacrol. Following a 6-week (42-day) experimental period, systemic necropsy was performed. Renal tissues were evaluated histopathologically using Periodic Acid–Schiff, Masson’s trichrome, and Best Carmine staining. Immunohistochemical analyses were conducted to assess Bcl-2, Bax, Caspase-3, Caspase-9 expression, and apoptotic cell death using the TUNEL assay. Results: Histopathological analysis demonstrated significant differences in tubular dilatation, intracellular vacuolization, and mesangial matrix expansion among groups (p < 0.05), whereas tubular atrophy, hyaline accumulation, mononuclear cell infiltration, and the number of sclerotic glomeruli were not significantly different (p > 0.05). Treatment with hesperidin and carvacrol significantly attenuated renal injury and fibrosis in diabetic rats (p < 0.001). Diabetic kidneys exhibited increased immunopositivity for Bax, Caspase-3, and Caspase-9 and decreased Bcl-2 expression (p < 0.001). Combined hesperidin and carvacrol treatment markedly reduced apoptotic cell numbers compared with the untreated diabetic group (p < 0.001). Conclusions: The combined administration of hesperidin and carvacrol exerts protective effects against diabetic nephropathy, potentially through modulation of the Bcl-2/Bax-mediated apoptotic pathway and attenuation of renal fibrosis. Full article

Naringinase is an enzyme complex composed of α-L-rhamnosidase and β-D-glucosidase, capable of deglycosylating flavonoids such as hesperidin. α-L-rhamnosidase converts hesperidin into rhamnose and hesperetin 7-O-glucoside (Hes-7-G), while β-D-glucosidase further hydrolyses Hes-7-G to hesperetin. Selective inactivation of β-D-glucosidase enables accumulation of Hes-7-G, a compound with higher water solubility and bioavailability than hesperidin or hesperetin, making it valuable for food and biotechnological applications. This study aimed to identify conditions allowing selective inhibition of β-D-glucosidase while preserving α-L-rhamnosidase activity for efficient Hes-7-G production. The effects of pH, temperature, and incubation time were investigated, together with the influence of polyols and sugars, including inositol, sucrose, glycerol, xylose, erythritol, xylitol, and sorbitol, on α-L-rhamnosidase thermostability. Among the tested additives, erythritol significantly improved α-L-rhamnosidase thermostability. The highest selectivity was achieved by incubating the enzyme in 1.4 M erythritol at 70 °C for 10 min, resulting in ~5% residual β-D-glucosidase activity and 50% α-L-rhamnosidase activity. Under these conditions, α-L-rhamnosidase activity exceeded β-D-glucosidase activity by more than 60-fold. Selective thermal inactivation of β-D-glucosidase in the presence of erythritol provides an effective strategy for producing Hes-7-G from hesperidin and may enhance flavonoid bioavailability for industrial applications. Full article

The genus Allium comprises more than 1100 species, where Allium ampeloprasum can be found. It is a species that, until now, has remained relatively unexplored, as well as its propagation organ known as Japanese garlic, even though it is increasingly cultivated in Mexico. The aim of this study was to evaluate phenolic profiles using Ultra-High-Performance Liquid Chromatography (UHPLC), as well as to conduct an exploratory study of total polyphenol content by Folin–Ciocalteu assay and antioxidant capacity by DPPH inhibition in husks, peeled and whole propagation organs subjected to different drying methods and extraction solvents. In order to observe the influence of these factors on polyphenol extraction using green extraction technologies, such as natural eutectic solvents (NADESs), it was observed that the drying method is crucial for the extraction of flavonoid-type polyphenols, while NADESs allowed for the selective extraction of antioxidant and anti-inflammatory compounds. The highest total polyphenol content was obtained in freeze-dried husks extracted with 60% hydrated NADES (384.81 ± 15.38 mg GAE/100 g). The greatest DPPH radical inhibition was observed in freeze-dried husks with 68% hydrated NADES (93.08 ± 0.58%), where polyphenols such as catechin, chlorogenic acid, rutin, quercetin + luteolin, kaempferol, and hesperidin stood out. This highlights the potential of the propagation organ of A. ampeloprasum, especially its husks, as a source of phenolic compounds, supporting the valorization of agro-industrial waste from garlic, since the results obtained exceed those previously reported for the Allium sativum variety. Full article

Breast cancer remains one of the most frequently diagnosed malignancies and a leading cause of cancer-related mortality among women worldwide. The growing interest in natural bioactive compounds has highlighted plant-derived phytochemicals as promising agents for cancer prevention and adjunctive therapy due to their pleiotropic biological activities and relatively low toxicity. In parallel, increasing attention has been directed toward agro-industrial by-products generated during food processing, which represent abundant and sustainable sources of valuable phytochemicals. This review provides a comprehensive overview of recent advances in the identification, extraction, and biological evaluation of phytochemicals derived from plants and agro-industrial residues, using pomegranate (Punica granatum) peels, onion (Allium cepa) skins, and citrus by-products as representative examples of phytochemical-rich agro-industrial residues. These by-products are rich in polyphenols, flavonoids, and other secondary metabolites—including punicalagins, ellagic acid, quercetin, hesperidin, and naringin—that have demonstrated significant antioxidant, anti-inflammatory, and anticancer properties. Recent in vitro and in vivo studies indicate that these compounds can modulate key molecular pathways involved in breast cancer initiation and progression, such as oxidative stress regulation, apoptosis induction, inhibition of cell proliferation, and suppression of signaling cascades including PI3K/Akt, NF-κB, and MAPK pathways. Furthermore, the valorization of agro-industrial waste offers a sustainable strategy to recover high-value bioactive compounds while reducing environmental impact. Overall, phytochemicals obtained from plant materials and food processing by-products represent promising functional agents for breast cancer prevention and therapy, although further studies are required to improve bioavailability, elucidate mechanisms of action, and validate their clinical potential. Full article

The expired drug Detralex (90% diosmin and 10% hesperidin), known as an effective corrosion inhibitor, was adsorbed onto mesoporous silica and incorporated into an epoxy matrix to enhance the coating’s corrosion protection in a highly corrosive 3 wt% NaCl solution. It was found that this treatment, by improving adhesion, modifying the hydrophilic properties, and enabling inhibitor release, increased the coating’s resistance over time. Based on an SEM-EDX analysis, even after 24 h of immersion, the epoxy coating with mesoporous nanosilica adsorbed with diosmin and hesperidin retained the incorporated inhibitors. This resulted in a slight increase in the samples’ polarization resistance during longer exposure. Full article

This study investigated the chemical composition of the essential oil (EO) and the phenolic profiles of methanol extracts from Satureja boissieri Hausskn. ex Boiss. EO analysis by Gas Chromatography–Mass Spectrometry (GC-MS) identified carvacrol (45.2%), cymene (26.0%) and γ-terpinene (17.5%) as the primary constituents. Phenolic profiles were quantified via Liquid Chromatography–High-Resolution Mass Spectrometry (LC-HRMS), revealing syringic acid (56,647.96 mg/kg extract), rosmarinic acid (47,777.98 mg/kg extract) and hesperidin (6353.49 mg/kg extract) as major components in the extract. The antioxidant potential was evaluated through three distinct radical scavenging assays (DPPH, ABTS and DMPD) and the determination of ferric (Fe³⁺) and cupric (Cu²⁺) reducing capacities. Notably, S. boissieri exhibited potent antioxidant activity, with IC₅₀ values of 11.74 µg/mL for DPPH and 9.90 µg/mL for ABTS radical scavenging, demonstrating performance comparable to standard antioxidants such as α-tocopherol (11.31 and 8.37 µg/mL, respectively). Furthermore, the in vitro inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were evaluated. While both extracts exhibited similar and significant AChE inhibition (35.3% and 32.4%, respectively), the essential oil was notably more potent against BChE than the methanol extract. These findings suggest that S. boissieri is a significant source of bioactive compounds with promising antioxidant and neuroprotective potential for pharmaceutical applications. Full article

The high consumption of citrus fruits generates large amounts of peel bioresidues, whose valorization represents an important strategy for sustainable agri-food systems. This study aimed to characterize the nutritional, chemical, and bioactive properties of flours obtained from orange (FL), tangerine (FT), lime (FLA), and lemon (FLO) peels, and to evaluate their potential as functional food ingredients. The flours were evaluated for proximate composition, organic acids, phenolic compounds, fatty acids, free sugars, and bioactive properties. Lime flour showed the highest protein, ash, dietary fiber, and total phenolic contents, with hesperidin identified as the predominant compound. The corresponding extracts exhibited relevant antioxidant, antimicrobial, antiproliferative, and nitric oxide (NO) production inhibitory activities, with lime flour presenting the strongest overall bioactive potential. Based on these results, lime flour was selected for application in a food model by partially replacing wheat flour (10% and 20%) in “Madalenas”, a traditional Portuguese muffin cake. The incorporation of lime flour improved product preservation compared with the control formulation and samples containing a synthetic preservative (potassium sorbate). These findings highlight the potential of citrus peel flours, particularly lime flour, as natural functional ingredients and sustainable alternatives for food formulations, contributing to waste valorization and circular economy approaches in the agri-food sector. Full article

Botanical extracts represent a rich and sustainable source of polyphenolic compounds with significant potential in anticancer research. Among these, hesperidin, naringenin, hydroxytyrosol, oleuropein, and quercetin have attracted considerable attention due to their abundance in widely consumed plants such as citrus fruits, olive derivatives, and various fruits and vegetables. However, their clinical translation is hindered by intrinsic limitations including poor solubility, low stability, and limited bioavailability. In this context, nanotechnology-based drug delivery systems have emerged as a promising strategy to enhance the therapeutic performance of these bioactive compounds. This review provides an overview of polyphenol-rich botanical matrices and focuses on recent advances in their nanoformulation. Various nanocarriers, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, and nanoemulsions, are discussed in terms of their ability to improve physicochemical properties, protect against degradation, and enhance delivery efficiency. Special attention is given to the challenges associated with the encapsulation of complex botanical extracts and the need to preserve their compositional integrity and synergistic effects. Overall, nanoformulation represents a powerful approach to overcome current limitations and unlock the full potential of plant-derived polyphenols in anticancer applications. Full article

The development of novel multifunctional emulsifiers using protein–polyphenol interactions is a common strategy. Previously, we investigated the emulsifying properties of the four citrus flavonoids alone. This study investigated how complexing lysozyme (LY) with four citrus-derived flavonoids affects emulsifying properties. Results demonstrated that the emulsification performance was enhanced when flavonoids were complexed with LY, following the order: hesperidin (Hpd) > neohesperidin dihydrochalcone (Neohpddic) > neohesperidin (Neohpd) > hesperetin (Hpt). This enhancement was positively correlated with the intrinsic emulsification abilities of the flavonoids, suggesting that the synergistic effect should not overlook the emulsifying capacity of the flavonoids themselves. The Hpd-LY mixture increased the three-phase contact angle (to near 90°) compared to Hpd alone (51.16° ± 0.58), which helped form high internal phase emulsion (HIPE) gels. Stable HIPEs were achieved at an oil phase fraction φ = 80%, mixture concentration w ≥ 0.8%, and Hpd-to-LY ratio k ≥ 1:1. Droplet size decreased as w increased from 0.6% to 1.2%, but increased with higher φ and k, while gel strength improved. In addition, these HIPEs protected encapsulated lutein and suppressed lipid oxidation. The findings show that flavonoid–protein complexes, especially Hpd-LY, can build stable and functional HIPEs for protecting bioactive compounds. Full article

Nowadays, the global demand for medicinal plants, including A. absinthium L. (wormwood), has increased considerably, leading to significant pressure on their wild populations and the biodiversity of ecosystems. Consequently, the rates of exploitation may exceed those of natural regeneration. This destructive process can be reduced by cultivating plants with the desired secondary metabolites by transferring them from their natural habitats. The present study investigates phytochemistry and the potential antioxidative/prooxidant activity of low-thujone A. absinthium plants. The chemical composition of wormwood extracts and essential oils (EOs) was determined by HPLC/DAD/TOF and GC/MS techniques, respectively. Trans-Sabinyl acetate (59.6 ± 10.1%) predominated in the wormwood EOs, while the content of toxic trans-thujone was negligible (1.2 ± 0.5%). Eighteen acids, such as fumaric, ascorbic, succinic, quinic, malic, gallic, benzoic, (neo/iso)chlorogenic, (di)ferulic, caffeic, etc., were found in 50% methanolic wormwood extracts. Additionally, (epi)catechin, astragalin, diosmetin, piceatannol-3’-O-glucoside, quercetin-3-O-glucoside, quercetin-3-O-rhamnoside-7-O-glucoside, hesperidin, apigenin-7-O-glucoside, baicalin, 5,7,3′-trihydroxy-3,6,4′,5′-tetramethoxyflavone and rutin were tentatively identified in the extracts. Total phenolic content was found 412.82 ± 11.10 mg/L (of gallic acid equivalent) in A. absinthium methanolic extracts. Using conventional spectroscopic methods, the antioxidant activity (DPPH radicals scavenging) was determined to be 0.83 ± 0.06 mmol/L (TROLOX equivalent) in the wormwood essential oil. ABTS^●+ and DPPH^● scavenging activity means, 3.485 ± 0.07 (TROLOX, mmol/L) and 6.48 ± 0.25 (TROLOX, mmol/L) were revealed for A. absinthium methanolic extracts. Less commonly used methods, electrochemical tests showed the presence of oxidizable compounds with characteristic E_pa values of 0.38 and 0.61 V. Moreover, hydrogen peroxide scavenging tests were performed. The largest quantity of peroxide (31.86 ± 0.1 μmol/L) was formed in the wormwood boiling infusions (at pH = 7.2). As the presence of toxic and neurotoxic thujone isomers is undesirable, therefore, the search for low- or thujone-free plants from natural populations that exhibit biological activity (i.e., antioxidant/prooxidant) is of great importance. Full article

The increasing global burden of cancer, together with the need for more sustainable resource management, has stimulated growing interest in the valorization of agro-industrial plant residues as sources of bioactive compounds with therapeutic potential. This review highlights the potential of plant by-products—including citrus peels, olive leaves, date palm residues, and tea and coffee processing wastes—as sustainable reservoirs of polyphenols and other phytochemicals with significant anticancer activity. Key compounds such as hesperidin and naringenin from citrus peels, oleuropein and hydroxytyrosol from olive leaves, quercetin and syringic acid from date palm residues, and chlorogenic acid and epigallocatechin gallate from tea and coffee by-products have demonstrated promising antitumor effects in both in vitro and in vivo studies. These molecules exert their activity through multiple mechanisms, including the inhibition of cancer cell proliferation, induction of apoptosis, regulation of the cell cycle, and modulation of major oncogenic signaling pathways such as PI3K/AKT, MAPK, NF-κB, and EGFR. For instance, hydroxytyrosol induces apoptosis and cell cycle arrest while inhibiting the PI3K/AKT and MAPK pathways. Quercetin limits metastasis and glycolysis and suppresses VEGF, PKM2, and AKT signaling. Ferulic acid suppresses tumor growth by inhibiting the PI3K/AKT and JAK2/STAT6 pathways, thereby promoting apoptosis (in vitro and in vivo). In addition to their pharmacological potential, the recovery of these compounds from plant waste supports circular economy strategies by reducing environmental impact and promoting the development of value-added products. Future research should focus on optimizing extraction methods, improving bioavailability and stability, and validating safety and efficacy through well-designed preclinical and clinical studies. Full article

Enriching honey with plant additives allows for increasing its antioxidant potential in an additive-dependent manner and at the same time shaping new sensory properties, increasing consumer acceptability. Known spices and by-products from fruit processing can also be used to produce such additives. Combined dry extracts of clove buds and mandarin peels were used to enrich antioxidant properties and to flavor rapeseed honey. Four different extracts combining both raw products were produced by ultrasound-assisted extraction using 50% vol. ethanol and converted into powder by vacuum concentration followed by lyophilization. The obtained extracts were evaluated for antioxidant activity (FRAP and DPPH assays) as well as total polyphenols content. Phenolic HPLC-DAD profiles were compared and selected polyphenols (syringic acid, ellagic acid, hesperidin and eugenol) were quantified. The dry extracts were incorporated into rapeseed honey (0.25% w/w) during the creaming process. No significant changes in color and texture were visually noted; whereas, some changes (p < 0.05) in titrable acidity and electrical conductivity were observed. A significant increase (p < 0.05) in antioxidant activity (from 4 to 6-fold) and the beneficial enrichment with well-known bioactive compounds (mainly eugenol and hesperidin) was observed for all produced flavored honeys. Moreover, tested properties of the enriched honeys remained stable during 6 months of storage. The two honeys with the most improved antioxidant activity showed better sensory characteristics and consumer acceptability compared to pure rapeseed honey, but slight extract type-dependent differences were noted. It was shown that the proposed sustainable technological process using waste mandarin peels can lead to the development of a new product referred to as “plant-enriched honey” with increased health-promoting value belonging to the functional food segment. Full article

Background/Objectives: Fingered citron (Citrus medica L. var. sarcodactylis (Siebold ex Hoola van Nooten) Swingle) is rich in phenolic constituents, yet systematic comparisons of free and bound phenolics across tissues and origins remain limited. This study compared the peel, pulp, and blend (whole fruit) of fingered citron from five Chinese regions: Zhejiang (ZJ), Yunnan (YN), Sichuan (SC), Guangdong (GD), and Guangxi (GX). Methods: Phenolic compositions were determined by colorimetric assays and HPLC. Antioxidant activity was assessed by ORAC and PSC, and hypoglycemic-related activity by α-glucosidase and α-amylase inhibition and glucose consumption in an insulin-resistant HepG2 (IR-HepG2) cell model. Results: Phenolic distribution followed the order peel > blend > pulp, and free > bound. HPLC identified 11 free and 5 bound phenolics, predominantly hesperidin, quercetin, and 5,7-dimethoxycoumarin. GX peel exhibited the highest free phenolic content (106.34 ± 0.23 mg GAE/100 g FW) and superior ORAC (30.56 ± 0.50 μmol TE/g FW), strongly correlating with total phenolics (r = 0.98, p < 0.01). Free phenolics showed stronger α-glucosidase and α-amylase inhibition, whereas bound phenolics produced higher glucose consumption in the IR-HepG2 cell model. The GX blend bound fraction showed the highest glucose consumption (5.48 ± 0.98 mmol/L). Conclusions: Under fresh-weight-based conditions, phenolic composition and in vitro bioactivities differed by fruit part, region, and phenolic fraction. Peel, especially GX peel, tended to show higher phenolic levels and stronger antioxidant-related performance, whereas the GX blend bound fraction showed the highest glucose-consumption-promoting activity. Full article