Search Results (25)

A set of procedures was developed for the simple synthesis of phytyl phenolipids, which resulted in high yields (70–95%) of phytyl esters of caffeic, protocatechuic, homoprotocatechuic, and dihydrocaffeic acids. Initial characterization revealed that these new compounds exhibited similar radical scavenging activity and liposolubility to α-tocopherol, a key antioxidant present in membranes. Cyclic voltammetry analysis indicated that the phytyl derivatives had lower anodic peak potentials compared to the original phenolic acids, with electron transfer following an adsorption-controlled mechanism. In phosphatidylcholine large unilamellar vesicles (LUVs), phytyl esters demonstrated remarkable efficiency in preventing liposome autoxidation when compared to α-tocopherol. Despite their strong radical scavenging capacity and membrane penetration ability, the antioxidant effectiveness of the phytyl esters in liposomes was influenced by the structure of their polyphenolic moiety. These new compounds are considered promising candidates for future pharmacological applications against oxidative stress in lipoproteins and cells, warranting further evaluation of their antioxidant and anti-inflammatory effects in cellular models and in vivo. Full article

γ-amino butyric acid (GABA) is an inhibitory neurotransmitter whose deficiency has been associated with various neurological disorders. However, its low liposolubility limits its use as a supplement. Thus, multiple investigations have focused on searching for lipophilic GABA analogs that can modulate the activity of the GABA_B receptor, which could be associated with the etiology of some central nervous system disorders. The GABA analogs available on the market are Vigabatrin, Gabapentin as well as Pregabalin and Baclofen. In this work, we report on the synthesis of GABA analogs, taking the scaffold of GABA, Pregabalin, and Baclofen as a starting point. The analogs include structural features that could favor the affinity of the molecules for the GABA_B receptor, such as heterocyclic rings in the γ-position and alkyl or p-Cl-phenyl substituents (in analogy to Pregabalin and Baclofen, respectively). These analogs were synthesized by a sequence of reactions involving an N-alkylation, a 1,4-conjugated addition of dialkyl and diarylcuprates and a basic hydrolysis. Furthermore, a computational molecular docking over the GABA_B receptor was performed to evaluate the interaction of each compound in the Baclofen binding site. With this information, we evaluated our compounds as GABA_B agonists through a QSAR analysis. Finally, by means of molecular similarity analysis, and in silico ADME prediction, we support our three best compounds (8a–b, 8d) as potential GABA_B receptor agonists. Full article

Danshen, a well-known traditional Chinese medicine (TCM), has gained increasing attention for its protective effects on nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms underlying these effects remain to be elucidated. Niemann-Pick C1-like 1 (NPC1L1), a key transporter mediating intestinal cholesterol absorption, has emerged as a critical target for NAFLD treatment. This study aimed to screen for NPC1L1 inhibitors from Danshen and investigate their therapeutic effects on NAFLD. We established a high-throughput screening platform using stable Caco2 cell lines expressing human NPC1L1 (hL1-Caco2) and discovered that tanshinones (Tans), the liposoluble components of Danshen, inhibited NPC1L1-mediated cholesterol absorption in hL1-Caco2 cells. Additionally, Tans treatment reduced hepatic steatosis in high-fat diet (HFD)-fed mice. To identify the active compounds in Tans, activity-oriented separation was performed by integrating the high-throughput screening platform and two-dimensional chromatographic techniques. Ultimately, cryptotanshinone (CTS) was identified as a novel NPC1L1 inhibitor and significantly decreased hepatic steatosis in HFD-fed mice. Molecular docking and dynamics simulation showed that CTS stably bound with NPC1L1, where TRP383 acted as the key amino acid. Taken together, this study demonstrates, for the first time, that CTS, a liposoluble compound from Danshen, is a novel NPC1L1 inhibitor. Our findings suggest that the inhibitory effect of CTS against NPC1L1-mediated intestinal cholesterol absorption may be a potential mechanism, contributing to its alleviation of NAFLD in mice. Full article

The goal of this research was nutritional evaluation through the phytochemical analysis of blackberry and raspberry leaves, the screening of their biological activity (antioxidant capacity and inhibition of lipid peroxidation), and the investigation of the effect of in vitro gastrointestinal digestion (GID) of blackberry and raspberry leaves on the bioaccessibility of polyphenol subclasses. The concentrations of the analyzed liposoluble antioxidants were higher (p < 0.05) in blackberry leaves compared to raspberry leaves, while a significant (p < 0.05) higher content of water-soluble antioxidants was registered in raspberry leaves (with a total polyphenol content of 26.2 mg GAE/g DW of which flavonoids accounted for 10.6 mg/g DW). Blackberry leaves had the highest antioxidant capacity inhibition of the superoxide radicals (O₂^•−), while raspberry leaves registered the highest inhibition of hydroxyl radicals (^•OH), suggesting a high biological potency in scavenging-free radicals under in vitro systems. The maximum inhibition percentage of lipid peroxidation was obtained for blackberry leaves (24.86% compared to 4.37% in raspberry leaves), suggesting its potential to limit oxidative reactions. Simulated in vitro digestion showed that hydroxybenzoic acids registered the highest bioaccessibility index in the intestinal phase of both types of leaves, with gallic acid being one of the most bioaccessible phenolics. The outcomes of this investigation reveal that the most significant release of phenolic compounds from blackberry and raspberry leaves occurs either during or after the gastric phase. Knowledge about the bioaccessibility and stability of polyphenol compounds during digestion can provide significant insights into the bioavailability of these molecules and the possible effectiveness of plant metabolites for human health. Full article

Enzymatic lipophilization has been proposed as a cost-effective strategy to produce new liposoluble antioxidant compounds. In this study, modified oils rich in structured phenolipids were prepared via one-pot enzymatic acylation of hydroxytyrosol (HTYR), vanillyl alcohol (VA) and homovanillyl alcohol (HVA) with pomace olive oil (POO) in solvent-free conditions using immobilized lipase on biogenic nanoparticles. The effect of temperature (30–70 °C) and enzyme concentration (0.1–1%, w/w) on the efficiency of the bioprocess as well as the reusability of the nanobiocatalyst were thoroughly investigated. The modified oils exhibited increased antioxidant activity compared to the control oil according to DPPH and CUPRAC assays (p < 0.05). The oxidative stability of pomace olive oil was also significantly enhanced after modification, as depicted by the K₂₃₂ values and TBARS contents under accelerated oxidation at 60 °C (p < 0.05). Moreover, a fortified mayonnaise containing modified oil with HTYR was prepared that was noticeably stable compared to the control mayonnaise at 28 °C for 5 months (p < 0.05). Enzymatically modified oils have great potential for application in the nutraceutical and food industry, encouraging the exploitation of immobilized lipases as effective and green catalytic tools. Full article

Based on the marine natural products piperafizine B, XR334, and our previously reported compound 4m, fourteen novel 3,6-diunsaturated 2,5-diketopiperazine (2,5-DKP) derivatives (1, 2, 4–6, 8–16), together with two known ones (3 and 7), were designed and synthesized as anticancer agents against the A549 and Hela cell lines. The MTT assay results showed that the derivatives 6, 8–12, and 14 had moderate to good anticancer capacities, with IC₅₀ values ranging from 0.7 to 8.9 μM. Among them, compound 11, with naphthalen-1-ylmethylene and 2-methoxybenzylidene functions at the 3 and 6 positions of 2,5-DKP ring, respectively, displayed good inhibitory activities toward both A549 (IC₅₀ = 1.2 μM) and Hela (IC₅₀ = 0.7 μM) cancer cells. It could also induce apoptosis and obviously block cell cycle progression in the G2/M phases in both cells at 1.0 μM. The electron-withdrawing functions might not be favorable for the derivatives with high anticancer activities. Additionally, compared to piperafizine B and XR334, these semi-N-alkylated derivatives have high liposolubilities (>1.0 mg mL⁻¹). Compound 11 can be further developed, aiming at the discovery of a novel anticancer candidate. Full article

Poor aqueous solubility, stability and bioavailability of interesting bioactive compounds is a challenge in the development of bioactive formulations. Cellulose nanostructures are promising and sustainable carriers with unique features that may be used in enabling delivery strategies. In this work, cellulose nanocrystals (CNC) and cellulose nanofibers were investigated as carriers for the delivery of curcumin, a model liposoluble compound. Nanocellulose modification with the surfactant cetyltrimethylammonium bromide (CTAB), tannic acid and decylamine (TADA), and by TEMPO-mediated oxidation were also tested and compared. The carrier materials were characterized in terms of structural properties and surface charge, while the delivery systems were evaluated for their encapsulation and release properties. The release profile was assessed in conditions that mimic the gastric and intestinal fluids, and cytotoxicity studies were performed in intestinal cells to confirm safe application. Modification with CTAB and TADA resulted in high curcumin encapsulation efficiencies of 90 and 99%, respectively. While no curcumin was released from TADA-modified nanocellulose in simulated gastrointestinal conditions, CNC-CTAB allowed for a curcumin-sustained release of ca. 50% over 8 h. Furthermore, the CNC-CTAB delivery system showed no cytotoxic effects on Caco-2 intestinal cells up to 0.125 g/L, meaning that up to this concentration the system is safe to use. Overall, the use of the delivery systems allowed for the reduction in the cytotoxicity associated with higher curcumin concentrations, highlighting the potential of nanocellulose encapsulation systems. Full article

Boron-containing compounds (BCC), particularly boronic acids and derivatives, are being increasingly tested as diagnostic and therapeutic agents. Some effects of BCC involve phenomena linked to the action of steroid or thyroid hormones; among these, are the effects on muscle mass or basal metabolism. Additionally, some toxicology reports on mammals, including humans, sound an alert concerning damage to several systems, among which are the negative effects on the induction of male infertility. Systemic and local mechanisms to explain changes in metabolism and impaired fertility were collected and presented. Then, we presented the putative pharmacodynamic and pharmacokinetic mechanisms involved and demonstrated in these events. In addition, it is proposed that there are adducts of some oxygenated BCC with cis-diols in fructose, an essential source of energy for sperm–cell motility, an uncoupling of sex hormone-binding globulin (SHBG) and its ligands, and the modulation of the DNA synthetic rate. These effects share the reactivity of boron-containing compounds on the cis-diols of key molecules. Moreover, data reporting no DNA damage after BCC administration are included. Further studies are required to support the clear role of BCC through these events to disrupt metabolism or fertility in mammals. If such phenomena are confirmed and elucidated, an advance could be useful to design strategies for avoiding BCC toxicity after BCC administration, and possibly for designing metabolism regulators and contraceptive drugs, among other purposes. Boronic derivatives and carboranes have been proposed and studied in this field. Full article

Although solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been successfully used as drug delivery systems for about 30 years, the usage of these nanoparticles as food-grade nanovehicles for nutraceuticals or bioactive compounds has been, relatively speaking, scarcely investigated. With fast-increasing interest in the incorporation of a wide range of bioactives in food formulations, as well as health awareness of consumers, there has been a renewed urge for the development of food-compatible SLNs and/or NLCs as nanovehicles for improving water dispersibility, stability, bioavailability, and bioactivities of many lipophilic nutraceuticals or poorly soluble bioactives. In this review, the development of food-grade SLNs and NLCs, as well as their utilization as nanosized delivery systems for lipophilic or hydrophobic nutraceuticals, was comprehensively reviewed. First, the structural composition and preparation methods of food-grade SLNs and NLCs were simply summarized. Next, some key issues about the usage of such nanoparticles as oral nanovehicles, e.g., incorporation and release of bioactives, oxidative stability, lipid digestion and absorption, and intestinal transport, were critically discussed. Then, recent advances in the utilization of SLNs and NLCs as nanovehicles for encapsulation and delivery of different liposoluble or poorly soluble nutraceuticals or bioactives were comprehensively reviewed. The performance of such nanoparticles as nanovehicles for improving stability, bioavailability, and bioactivities of curcuminoids (and curcumin in particular) was also highlighted. Lastly, some strategies to improve the oral bioavailability and delivery of loaded nutraceuticals in such nanoparticles were presented. The review will be relevant, providing state-of-the-art knowledge about the development of food-grade lipid-based nanovehicles for improving the stability and bioavailability of many nutraceuticals. Full article

Fuzhuan brick tea (FBT), a type of black tea, is a traditional beverage in China, especially popular among frontier ethnic groups. FBT is well-known for its health benefits, such as hypoglycemic, anti-hypertensive, anti-inflammatory, diuretic, and detoxification effects. Nevertheless, the underlying mechanisms on the molecular level are still elusive and the key compounds responsible for the health benefits are unidentified. Previous studies have mainly focused on functional studies of the water extract. However, FBT is typically cooked with butter or milk. Therefore, we hypothesized that some lipophilic components in FBT, which can be absorbed through the co-consumption of butter or milk, may play an important role in the health benefits. The present study aimed to investigate whether the liposoluble extract of FBT alleviates symptoms related to metabolic diseases and to identify the active compounds involved. By comparing the high-performance liquid chromatography (HPLC) profiles of water, milk and hexane extract, some low polarity peaks were observed in the milk and hexane extracts. Furthermore, the hexane extract treatment alleviated body weight gain, serum total cholesterol and triglyceride levels, and inhibited the accumulation of hepatic fat granules in a high-fat diet (HFD)-induced C57BL/6N mouse model. In order to identify the key functional lipophilic compounds in FBT, the hexane extract of FBT was subjected to chemical characterization. Four phenol analogs were characterized, namely, isodihydroauroglaucin (1), dihydroauroglaucin (2), tetrahydroauroglaucin (3), and flavoglaucin (4). Compounds 1 and 4 reduced the levels of total cholesterol and triglyceride in vivo. Both compounds also inhibited the high-fat diet-induced body weight gain and accumulation of fat granules in the liver of C57BL/6N mice. Isodihydroauroglaucin and flavoglaucin have therefore been identified as bioactive ingredients that contribute to the health benefits of FBT. Full article

In the Supercritical Antisolvent process (SAS), the thermodynamic behavior of complex multicomponent systems can influence the particles’ morphology. However, due to the limited thermodynamic data for multicomponent systems, the effect of solutes is often neglected, and the system is considered as pseudo-binary. It has been demonstrated that the presence of a solute can significantly influence the thermodynamic behavior of the system. In particular, when the SAS process is adopted for the production of drug/polymer coprecipitated microparticles, the effect of both the drug and the polymer in the solvent/CO₂ mixture should be considered. In this work, the effect of polyvinylpyrrolidone (PVP), used as the carrier, and of the liposoluble vitamins menadione (MEN) and α-tocopherol (TOC), as model drugs, was investigated as a deviation from the fundamental thermodynamic behavior of the DMSO/CO₂ binary system. Vapor–liquid equilibria (VLE) were evaluated at 313 K, with a PVP concentration in the organic solution equal to 20 mg/mL. The effect of the presence of PVP, MEN, and TOC on DMSO/CO₂ VLE at 313 K was studied; furthermore, the effect of PVP/MEN and PVP/TOC, at a polymer/drug ratio of 5/1 and 3/1, was determined. Moreover, SAS precipitation experiments were performed at the same polymer/drug ratios using a pressure of 90 bar. Thermodynamic studies revealed significant changes in phase behavior for DMSO/CO₂/PVP/TOC and DMSO/CO₂/PVP/MEN systems compared to the binary DMSO/CO₂ system. From the analysis of the effect of the presence of a single compound on the binary system VLE, it was noted that PVP slightly affected the thermodynamic behavior of the system. In contrast, these effects were more evident for the DMSO/CO₂/TOC and DMSO/CO₂/MEN systems. SAS precipitation experiments produced PVP/MEN and PVP/TOC microparticles, and the obtained morphology was justified considering the quaternary systems VLE. Full article

Carotenoids are organic, liposoluble pigments found in nature, which are responsible for the characteristic colors of ripe tomatoes, carrots, peppers, and crustaceans, among others. Palliative care provided to patients with an incurable disease is aimed at improving the patient’s quality of life through appropriate treatment of symptoms accompanying the disease. Palliative care patients with burdensome symptoms related to advanced-stage cancers are especially interested in the use of natural dietary supplements and herbal remedies to reduce symptoms’ intensity and ameliorate the quality of life. Carotenoids seem to be a group of natural compounds with particularly promising properties in relieving symptoms, mainly due to their strong antioxidant, anti-inflammatory, and neuroprotective properties. Moreover, carotenoids have been used in folk medicine to treat various diseases and alleviate the accompanying symptoms. In this narrative review, the authors decided to determine whether there is any scientific evidence supporting the rationale for carotenoid supplementation in advanced-stage cancer patients, with particular emphasis on the adjuvant treatment of cancer-related symptoms, such as neuropathic pain and cancer-related cachexia. Full article

Unprecedented nanoemulsion formulations (NE) of Jasminum humile and Jasminum grandiflorum essential oils (EO) were prepared, and examined for their cytotoxic and antiviral activities. NE characterization and stability examination tests were performed to ensure formula stability. The antiviral activity was determined against hepatitis A (HAV) and herpes simplex type-1 (HSV-1) viruses using MTT assay, while the cytotoxic potential was determined against liver (HepG-2), breast (MCF-7), leukemia (THP-1) cancer cell lines and normal Vero cells. Statistical significance was determined in comparison with doxorubicin as cytotoxic and acyclovir as antiviral standard drugs. GC-MS analysis indicated twenty four compounds in the EO of J. humile and seventeen compounds in the EO of J. grandiflorum. Biological investigations of pure EOs revealed weak cytotoxic and antiviral effects. Nevertheless, their NE formulations exhibited high biological value as cytotoxic and antiviral agents. NE formulations also showed feasible selectivity index for the viral-infected and cancer cells (especially HepG-2) than normal Vero cells. Both nanoemulsions showed lower IC₅₀ than standard doxorubicin against HepG-2 (26.65 and 22.58 vs. 33.96 μg/mL) and MCF-7 (36.09 and 36.19 vs. 52.73 μg/mL), respectively. The study results showed the dramatic effect of nanoemulsion preparation on the biological activity of EOs and other liposoluble phytopharmaceuticals. Full article

Background and Objectives: The present study demonstrates that apart from the well-known toxicity of liposoluble vitamins, some hydrosoluble vitamins may also exert toxicity; thus, routine supplementation with vitamins or ingestion of fortified foods should not be considered harmless. The study addresses the possible correlations between the physico-chemical properties and the side effects of vitamins when taken in high doses or for a too long a period. Materials and Methods: The FAFDrugs4.0 computational tool was used for computational assessment of the ADMET profile of several hydro- and liposoluble vitamins. Results: ADMET analysis revealed the following major data: vitamin B3 and B13 showed reduced structural complexity; thus, a relative toxicological potential may be exerted. Vitamins B1 and B7 were found to have good oral absorption and thus good bioavailability, while Vitamin B3 was found to have decreased oral absorption. In addition, all of the liposoluble vitamins reflected higher complexity, much greater than most of the potentially therapeutically-proven compounds. Conclusions: The present study emphasizes the importance between the physico-chemical properties of vitamins and their possible toxicological impact. Full article

Poor aqueous solubility of bioactive compounds is becoming a pronounced challenge in the development of bioactive formulations. Numerous liposoluble compounds have very interesting biological activities, but their low water solubility, stability, and bioavailability restrict their applications. To overcome these limitations there is a need to use enabling delivering strategies, which often demand new carrier materials. Cellulose and its micro- and nanostructures are promising carriers with unique features. In this context, this review describes the fast-growing field of micro- and nanocellulose based delivery systems with a focus on the release of liposoluble bioactive compounds. The state of research on this field is reviewed in this article, which also covers the chemistry, preparation, properties, and applications of micro- and nanocellulose based delivery systems. Although there are promising perspectives for introducing these materials into various fields, aspects of safety and toxicity must be revealed and are discussed in this review. The impact of gastrointestinal conditions on the systems and on the bioavailability of the bioactive compounds are also addressed in this review. This article helps to unveil the whole panorama of micro- and nanocellulose as delivery systems for liposoluble compounds, showing that these represent a great promise in a wide range of applications. Full article