Search Results (163)

The aging population and increasing prevalence of oxidative stress-related diseases underscore the need for functional food and pharmaceutical formulations enriched with bioactive compounds. This study aimed to design sustainable emulsion systems incorporating enzymatically modified fats with enhanced functional and bioactive properties. Enzymatic interesterification was employed as an environmentally friendly alternative to chemical catalysis, enabling the transformation of natural lipids without generating undesirable trans isomers. The lipid phase was formulated from blends of hemp oil, a plant-derived source rich in polyunsaturated fatty acids with documented antioxidant potential, and mutton tallow, in an effort to valorize meat industry by-products. Systematic evaluation of emulsion stability, viscosity, and textural properties was conducted using Turbiscan analysis and texture profile analysis. The results demonstrated that xanthan gum concentration was the primary determinant of structural stability, physicochemical stability, and structural integrity of the emulsion systems. Formulation no. 38 (0.8% w/w xanthan gum) was identified as the statistically most stable system based on Turbiscan Stability Index values (TSI = 1.4). Although emulsions containing 1.0% w/w xanthan gum exhibited similarly low TSI values and slightly smaller final droplet diameters, formulation E38 showed the smallest increase in droplet size during storage (<1 µm), indicating superior resistance to structural changes over time. Fat composition showed minimal influence on emulsion behavior, suggesting that lipid selection should prioritize nutritional and bioactive value. These findings indicate that emulsions based on enzymatically modified fats and stabilized with natural polysaccharides can serve as physically stable systems with potential applicability in food, cosmeceutical, and pharmaceutical formulations intended for bioactive compound delivery. Full article

Marine-derived fungi have become a vital resource for the discovery of novel secondary metabolites with diverse structures and significant biological activities. This study focuses on a systematic chemical investigation of the sponge-associated fungus Talaromyces stipitatus HF05001, leading to the isolation and identification of 20 compounds, including one new marine ketal natural product (Compound 17, Talarobispiral A). These compounds were structurally elucidated using comprehensive spectroscopic analyses, including 1D and 2D NMR, HRESIMS. All isolates were screened for their anti-inflammatory and anti-adipogenic properties. Among them, compound 4 (Secalonic acid D, SAD), 7 (Sch 725680) and 16 (bacillisporins C) demonstrated significant anti-inflammatory potential by markedly suppressing nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Notably, compound 4 showed superior inhibitory effect, with an IC₅₀ value of 0.22 μM. Additionally, compound 4 exhibited the strongest dose-dependent inhibition of lipid droplet accumulation in 3T3-L1 preadipocytes. These findings highlight the dual therapeutic potential of metabolites from Talaromyces stipitatus, identifying promising lead compounds for the development of novel treatments for inflammatory and metabolic disorders. Full article

Background/Objectives: Mature adipocytes were previously regarded as terminally differentiated cells that are restricted to lipid storage. Recent studies have shown that they can dedifferentiate into fibroblast-like progenitor cells, termed dedifferentiated fat (DFAT) cells. These cells exhibit stem cell-like properties and multilineage potential, highlighting their promising role in regenerative medicine and disease pathology. This systematic review aims to explore and consolidate the evidence regarding mechanisms, culture methods, pathophysiological roles, and therapeutic potential of adipocyte dedifferentiation. Methods: A systematic review was conducted in PubMed using the terms “dedifferentiation”, “de-differentiation”, “transdifferentiation”, and related variants in combination with “adipocyte”. Studies were screened and selected according to the PRISMA 2020 guidelines. Non-English articles, non-full texts, and non-review papers were excluded. After duplicate removal and eligibility assessment, 53 studies were included. Further, these were classified into categories according to their abstracts. Results: The evidence from the included articles indicates that mature adipocytes can dedifferentiate both in vitro, via ceiling culture, and in vivo, yielding DFAT cells with proliferative and multilineage differentiation capacity. Dedifferentiation involves lipid droplet secretion (liposecretion) and is characterized by downregulation of adipogenic genes such as PPARG and C/EBPα, alongside upregulation of proliferation, stemness, and lineage-associated markers. Functionally, DFAT cells contribute positively to tissue regeneration and wound repair, but they can drive adverse outcomes such as fibrosis, insulin resistance, and tumor progression through signaling pathways, including Wnt/β-catenin and TGF-β. Conclusions: Mature adipocyte dedifferentiation marks a dynamic reprogramming mechanism with dual roles—beneficial in regenerative medicine and wound healing, yet detrimental in cancer and metabolic disease. Further research is required to identify in vivo regulators, establish definitive markers, and translate adipocyte plasticity into regenerative medicine applications. Full article

Objective: Acteoside (ACT) has different pharmacological properties such as antioxidant, hepatoprotective and anti-inflammatory effects. Impaired mitophagy has been recognized as an important pathogenic factor in metabolic dysfunction-associated steatotic liver disease (MASLD). Nevertheless, the possible therapeutic role of ACT in MASLD and the exact effect of ACT on mitophagy regulation are not explored. This study aims to elucidate the therapeutic efficacy of ACT in a high-fat and high-sugar (HFHS) diet-induced mouse model of MASLD and to determine whether its effects are related to the activation of PINK1/Parkin-related mitophagy markers. Methods: C57BL/6J mice were randomly allocated to control, model, rosuvastatin (RSF, 3 mg/kg), and ACT (30, 60, and 120 mg/kg) groups. Following a 14-week continuous intervention, biochemical parameters, liver histology, and mitophagy-related markers were assessed. Results: ACT administration significantly improved serum lipid profiles, liver function and insulin resistance, marked by reduced levels of MDA, IL-6, TNF-α, IL-1β, LDL-C, TC, TG, AST, ALT, HOMA-IR (p < 0.05), while increasing HDL-C and enhancing hepatic GSH-Px and SOD activities (p < 0.05). Histological examination revealed a notable attenuation of hepatic steatosis and lipid accumulation. At the molecular level, ACT promoted mitophagy activation, as indicated by upregulated PINK1, LC3II/I, and Parkin expression and downregulated P62 and p-P62. Electron microscopy further validated the restoration of mitochondrial morphology and reduction in lipid droplets. Conclusions: These results demonstrate that ACT ameliorates MASLD progression by improving metabolic homeostasis, reducing inflammation and oxidative stress, and alleviating PINK1/Parkin-related mitophagy impairment to restore mitophagy homeostasis. Our study highlights the potential of ACT as a new therapeutic agent for MASLD. Full article

Background: Recent studies have shown that plant-based dietary extracts can prevent the formation of lipid droplets (LDs) and oxidized lipid droplets (oxLDs) in liver cells. These results indicate that these extracts might be useful in addressing metabolic dysfunction-associated fatty liver disease (MAFLD) and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH). In our ongoing study, we evaluated the potential of various food extracts to inhibit the accumulation and oxidation of LDs in liver cells to prevent metabolic MAFLD and MASH. Methods: The antioxidant activity index was determined using the DPPH assay, cell viability was assessed via cytotoxicity and lipotoxicity, and lipid droplet accumulation inhibition (LDAI) assays were performed. Metabolome analysis was performed using 1D-NMR [¹H, ¹³C, DEPT 90, and 135] techniques. Results: Dietary clove (Syzygium aromaticum) extract exhibited antioxidant properties and inhibited linoleic acid-induced lipid droplet (LD) accumulation (LDA) and oxidized LDA (oxLDA) in HepG2 cells. Additionally, an analysis of the metabolome of dietary clove bioactive LDAI using 1D-NMR showed that clove extract (CE) mainly consists of hydroxybenzoic acids (HBAs) and hydroxycinnamic acids (HCAs), along with minor amounts of carbohydrates, coumarins, polyphenolic compounds, and small quantities of polyols, fatty acyls, small peptides, and amino acids. This suggests that CE could be a promising resource for developing functional foods and nutraceuticals and discovering drugs for treating MAFLD, MASH, and related conditions. Full article

Background/Objectives: Leishmaniasis is a neglected parasitic disease with significant global impact and limited therapeutic options due to the toxicity and cost of current treatments. Antimicrobial peptides (AMPs) derived from amphibians, such as Ocellatin-PT4 and Ocellatin-PT6, have emerged as promising bioactive molecules due to their antimicrobial properties and low toxicity to mammalian cells. This study evaluated the leishmanicidal and immunomodulatory effects of Ocellatin-PT4 and Ocellatin-PT6 against Leishmania amazonensis amastigotes. Methods: Peptides were tested on axenic amastigotes and macrophages infected with amastigotes. Cytotoxicity was assessed using MTT (0.4–197 µM for Ocellatin-PT4 and 0.3–152.1 µM for Ocellatin-PT6) and vital dye exclusion assays. Reactive oxygen species (ROS), nitric oxide (NO), and lipid droplet (LD) production were quantified to assess immunomodulatory responses. Results: Ocellatin-PT4 and Ocellatin-PT6 significantly reduced the viability of free and intracellular amastigotes at concentrations ≥ 24.7 µM and ≥19 µM, respectively, without affecting J774 macrophage viability. Infected macrophages treated with the peptides showed reduced parasite load and decreased infection index (≥12.3 µM for Ocellatin-PT4 and ≥2.4 µM for Ocellatin-PT6). Both peptides modulated the oxidative stress response: they reduced ROS levels in infected macrophages while only slightly increasing NO production at higher concentrations. Additionally, lipid droplet accumulation, which was increased during infection, was downregulated by both peptides—particularly by Ocellatin-PT6. Conclusions: Ocellatin-PT4 and Ocellatin-PT6 exert leishmanicidal effects and modulate key macrophage functions without cytotoxicity. These peptides represent promising candidates for the development of novel therapies against cutaneous leishmaniasis. Full article

Polysaccharide intervention is an effective strategy to regulate properties of emulsions. In this study, xanthan gum (XG), konjac glucomannan (KGM), guar gum (GG), and inulin (IN) were selected to regulate physical and gastrointestinal digestive properties of sodium caseinate (CAS) oil-in-water (O/W) emulsions. The results indicate that IN could not improve CAS emulsion properties, while XG, KGM, and GG significantly reduced droplet size and improved emulsions’ stability. With the increase of the polysaccharide concentration, the G′ and G″ of the emulsions increased and the emulsions showed an obvious “solid-like” state, which effectively slowed down the “strain-thinning” phenomenon. The microstructure demonstrated that the polysaccharide chains are effectively connected with the surface membrane of droplets, which effectively improves interfacial membrane strength and inhibits droplet aggregation. In vitro digestion simulations proved that polysaccharides effectively modulate emulsion lipid release, providing an excellent lipid environment for curcumin absorption in the gastrointestinal tract. The order of the four polysaccharides in improving CAS emulsions was XG > KGM > GG > IN. This study dissects the differential regulation of physical and gastrointestinal digestive properties of emulsion by polysaccharides, providing theoretical support for functional emulsions for diverse requirements. Full article

The global increase in the older population presents a nutritional challenge; therefore, the development of food products for this group must take into account the physiological changes associated with aging. This work aimed to evaluate the effects of droplet size, conventional emulsion (CE) and nanoemulsion (NE), and different hydrocolloids, soy protein (SPI), whey protein (WPI), agar (AG), and κ-carrageenan (CAR), on the physical properties, lipid digestibility, and bioaccessibility of emulsion-based gels enriched with vitamin D. The main findings indicated that all gels exhibited non-Newtonian behavior and suitable viscosity and texture for the swallowing needs of older people. The highest release of free fatty acids (~30%) was observed in the NE + WPI sample, independent of droplet size. Instead, SPI gels showed the highest vitamin D bioaccessibility, likely due to their less-structured gel network. Thus, gels containing WPI + AG provide a favorable balance between an easy-to-swallow texture and efficient nutrient release, making them suitable for producing food based on emulsion-filled gels with good physical and nutritional properties. Hence, these results highlight the potential of tailored hydrocolloid combinations to develop nutrient-fortified and texture-appropriate gels that address the nutritional needs of the older population. Full article

Brown adipose tissue (BAT) has shifted from being considered a transient thermogenic organ of infancy to a metabolically dynamic and multifunctional tissue throughout life. Histologically and developmentally distinct from white and beige adipocytes, BAT originates from a myogenic lineage and is characterised by a high mitochondrial density, multilocular lipid droplets, and abundant sympathetic innervation. Its defining function, non-shivering thermogenesis, is mediated by uncoupling protein 1 (UCP1) and complemented by alternative mechanisms such as futile creatine and calcium cycling. Beyond heat production, thermogenic fat is crucial in regulating whole-body metabolism. It contributes to glucose, lipid, and branched-chain amino acid homeostasis, and engages in endocrine and paracrine signalling through a rich secretome of batokines, lipid mediators, and extracellular vesicle-bound microRNAs. These signals orchestrate crosstalk with the liver, skeletal muscle, pancreas, and immune system, enhancing insulin sensitivity, vascularisation, and anti-inflammatory responses. Brown/Beige fat also exhibits notable anti-fibrotic properties and supports adipose tissue remodelling, maintaining structural and functional plasticity under metabolic stress. This review offers a comprehensive synthesis of thermogenic adipose tissue biology, integrating its structural, developmental, and molecular features with its expanding physiological functions, highlighting its pivotal role in energy balance as well as its emerging therapeutic potential in obesity, type 2 diabetes, and related metabolic disorders. Full article

Honokiol (HON) and magnolol (MAG), structural isomers from Magnolia officinalis, exhibit notable anticancer activity, particularly against head and neck squamous cell carcinoma (HNSCC). However, due to their high lipophilicity, their intravenous administration is challenging. This study aimed to develop HON- and MAG-loaded intravenous (IV) nanoemulsions using commercial lipid preparations with varying fatty acid compositions. The formulations were physicochemically characterized and evaluated in vitro using FaDu and SCC-040 HNSCC cell lines. HON and MAG were sterilized via ionizing radiation at doses of 25, 100, and 400 kGy. Their suitability for IV use was assessed through PXRD, DSC, TGA, EPR, FT-IR, NMR, and HPLC analyses. All formulations met safety criteria for IV administration, with mean droplet diameters below 241 nm and encapsulation efficiencies exceeding 95%. They significantly reduced cancer cell viability, with a synergistic effect observed in combined HON and MAG formulations compared to single-compound nanoemulsions. Clinoleic-based formulations showed enhanced anticancer efficacy, likely due to the pro-apoptotic properties of oleic acid. Notably, radiation sterilization at the standard 25 kGy dose preserved the thermal, crystalline, and structural stability of HON and MAG, whereas higher doses (400 kGy) induced degradation. Although free radicals were detected via EPR, their transient nature and rapid decay confirmed the method’s safety. HON/MAG-loaded nanoemulsions exhibited strong anticancer potential, while radiation sterilization at 25 kGy ensured sterility without compromising stability. These findings provide a preliminary in vitro basis for future in vivo studies investigating HON and MAG as potential adjuvant therapies for HNSCC. Full article

Background: Cucurbitacin E (CuE), a natural tetracyclic triterpenoid compound extracted from the melon stems of Cucurbitaceae plants, has been reported to exhibit anti-inflammatory and anti-cancer properties, along with the ability to enhance cellular immunity. However, its role and molecular mechanism in regulating lipid metabolism and adipogenesis remain unclear. This study aims to investigate the potential anti-adipogenic and anti-obesity effects of CuE in 3T3-L1 adipocytes. Materials and Methods: 3T3-L1 preadipocytes were cultured and induced to differentiate using a standard adipogenic cocktail containing dexamethasone, 3-isobutyl-1-methylxanthine (IBMX), and insulin (DMI). CuE was administered during the differentiation process at various concentrations. Lipid accumulation was assessed using Oil Red O staining, and cell viability was evaluated via the MTT assay. To determine whether CuE induced apoptosis or necrosis, flow cytometry was performed using annexin V/PI staining. Additional molecular analyses, such as Western blotting and RT-PCR, were used to examine the expression of key adipogenic markers. Results: Treatment with CuE significantly reduced lipid droplet formation in DMI-induced 3T3-L1 adipocytes in a dose-dependent manner, as shown by decreased Oil Red O staining. Importantly, CuE did not induce apoptosis or necrosis in 3T3-L1 cells at effective concentrations, indicating its safety toward normal adipocytes. Moreover, CuE treatment downregulated the expression of adipogenic markers such as PPARγ and C/EBPα at both mRNA and protein levels. Discussion: Our findings suggest that CuE exerts a non-cytotoxic inhibitory effect on adipocyte differentiation and lipid accumulation. This anti-adipogenic effect is likely mediated through the suppression of key transcription factors involved in adipogenesis. The absence of cytotoxicity supports the potential application of CuE as a safe bioactive compound for obesity management. Further investigation is warranted to elucidate the upstream signaling pathways and in vivo efficacy of CuE. Conclusions: Cucurbitacin E effectively inhibits adipogenesis in 3T3-L1 adipocytes without inducing cytotoxic effects, making it a promising candidate for the development of functional foods or therapeutic agents aimed at preventing or treating obesity. This study provides new insights into the molecular basis of CuE’s anti-obesity action and highlights its potential as a natural lipogenesis inhibitor. Full article

Protein-polyphenol-based delivery vehicles are effective strategies for encapsulating bioactive compounds, thereby enhancing their solubility and bioaccessibility. In this study, dihydromyricetin/soy protein isolate (DHM/SPI) complexes were used as emulsifiers to prepare Pickering emulsions for DHM delivery. The results show that DHM and SPI form negatively charged complexes through hydrogen bonding, and the complex size decreases and stabilizes with increasing DHM addition. The size of the emulsion droplets was inversely related to the concentration of DHM addition (c), particle concentration (w), and ionic strength (i). Conversely, the increasing oil phase concentration (φ) was positively correlated with droplet size. The CLSM results confirmed the expected oil-in-water emulsion, while the rheological behavior of the Pickering emulsion highlighted its elastic, gel-like network structure and non-Newtonian fluid properties. Moreover, DHM effectively slowed lipid oxidation in the emulsion, and the bioaccessibility of DHM reached 33.51 ± 0.31% after in vitro simulated digestion. In conclusion, this emulsion system shows promising potential for delivering DHM and harnessing its bioactive effects. Full article

α7 nAChRs are known to modulate several physiological and pathological functions in glial cells, and their selective activation might have anti-inflammatory effects in the central and peripheral nervous system. OL progenitors (OPCs) respond to cholinergic stimuli via muscarinic receptors that are mainly involved in the modulation of their proliferation. Conversely, the role of nicotinic receptors, particularly α7 nAChRs, has been poorly investigated. In this study, we evaluated the expression of α7 nAChRs in a model of OPCs (Oli neu) and the potential effects mediated by their selective activation. Methods: Oli neu cells were used as a murine immortalized OPCs model. The effects of α7 nAChRs stimulation on cell proliferation and survival were assessed by the MTT assay. RT-PCR and Western blot analysis were used to analyze the expression of α7 nAChRs and proliferative and differentiative markers (PCNA, MBP). LPS exposure was used to induce the environment in which the antioxidant and anti-inflammatory properties of α7 nAChRs were analyzed, evaluating NFR2 and TNF-α expression, ROS levels through DCFDA staining while Oil Red O staining was used for the analysis of lipid droplet content as a marker of cellular inflammation response. Results: The α7 nAChR is expressed both in OPCs and OLs, and its stimulation by the selective agonist ICH3 increases cell proliferation without modifying the OLs’ differentiation capability. Moreover, ICH3 showed anti-inflammatory and antioxidant effects against LPS exposure. Conclusions: The results herein obtained confirm the role of α7 nAChR in the modulation of neuroinflammatory processes as well as their protective effects on OLs. Full article

Sarcopenic obesity (SO) is a metabolic disorder for which no effective pharmacological treatments are currently available. Cistanoside F (Cis), a phenoxyethanol-derived compound, remains relatively unexplored in the context of lipid metabolism regulation, as well as its potential mechanisms and therapeutic applications in metabolic disorders. Consequently, this study aimed to evaluate the potential of Cis in ameliorating the pathological manifestations of SO in C2C12 cells. Two classical adipogenic differentiation models using C2C12 cells were employed to quantitatively assess the ability of Cis to inhibit lipid droplet formation, utilizing Oil Red O staining coupled with high-content imaging analysis. Markers associated with adipogenic and myogenic differentiation were examined using quantitative real-time PCR and Western blotting. Our experimental findings demonstrated that Cis significantly attenuated lipid droplet accumulation and promoted muscle protein synthesis via the modulation of PPARγ, ATGL, CPT1b, and UCP1 expression during lipogenic differentiation of C2C12 cells. Cis significantly upregulated the phosphorylation and expression levels of key metabolic regulators, including p-AMPK/AMPK, p-ACC1/ACC1, and MHC. We identified a positive regulatory feedback mechanism between AMPK signaling and MHC expression in the adipogenic differentiation model, suggesting that Cis exerts its therapeutic effects through AMPK-dependent pathways. This is the first study to provide the first experimental evidence supporting the therapeutic potential of Cis for metabolic regulation, targeting adiposity reduction and muscle mass enhancement. Furthermore, Cis exhibited potent anti-inflammatory properties, as demonstrated by its ability to significantly downregulate proinflammatory mediators, including IL-6 and p-NF-κB/NF-κB, during adipogenic differentiation. These novel findings regarding the anti-inflammatory mechanisms of Cis will form the basis for our subsequent in-depth mechanistic investigations. Full article

The present study compared the free and encapsulated photosensitizer hypocrellin B (HB) in terms of photophysical-chemical properties, cellular uptake, subcellular distribution, and phototoxicity. The hydrophobic HB was encapsulated into liposomes (HB@Lipo) or poly (lactic-co-glycolic acid) nanoparticles (HB@PLGA). Encapsulation into nanocarriers exerted no obvious influence on the photophysical-chemical properties of HB, including UV-visible absorbance, fluorescence spectra, singlet oxygen (¹O₂) production capacity, and photostability. Free and encapsulated HB revealed some disparities in cellular uptake and subcellular localization patterns. In 2D-cultured B16 cells and tumor spheroids, free HB exhibited the fastest cellular uptake, while HB@PLGA had the lowest, as evidenced. Subcellular localization analysis first revealed a significant colocalization of free HB, HB@Lipo, and HB@PLGA within lipid droplets, with minimal colocalization in mitochondria and the endoplasmic reticulum. Unlike free HB and HB@Lipo, HB@PLGA exhibited strong lysosomal colocalization, indicating a unique intracellular trafficking pathway for PLGA-encapsulated HB. Upon laser irradiation, both free and encapsulated HB induced pronounced phototoxicity with substantial ROS production, confirming the robust PDT effect of HB. The photodynamic killing effect correlated with the intracellular HB content. These findings highlighted the impact of nanoformulation on HB’s cellular behavior and therapeutic performance. Full article