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Frontiers in Bioscience (Landmark... Jun 2024Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, often progressing to severe liver injury, for which approved...
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, often progressing to severe liver injury, for which approved treatments are currently lacking. This study explores the potential therapeutic impact of alpha-lipoic acid (ALA), a natural compound crucial in lipid metabolism, on NAFLD using an model.
METHODS
HepG2 cells were treated with a palmitic acid:oleic acid (PA:OA) mixture, representing a cellular model of steatosis. Subsequent treatment with ALA at concentrations of 1 µM and 5 µM aimed to evaluate its effects on lipid content and metabolism. Real-time polymerase chain reaction (PCR), BODIPY staining, cytofluorimetric analysis, and lipidomics were used to assess gene expression, lipid droplet accumulation, and fatty acid profiles.
RESULTS
Our results showed that ALA significantly reduced lipid droplets in PA:OA-treated HepG2 cells, with a concentration-dependent effect. Analysis of fatty acid profiles demonstrated a decrease in palmitic acid levels with ALA treatment, while oleic acid reduction was observed only at the higher concentration. Moreover, ALA modulated the expression of genes involved in cholesterol biosynthesis and low-density lipoprotein (LDL) metabolism, indicating a potential role in lipid homeostasis. Further insights into molecular mechanisms revealed that ALA modulated peroxisome proliferator activated receptors (PPARs), specifically PPAR-alpha and PPAR-gamma, involved in fatty acid metabolism and insulin sensitivity. Finally, ALA counteracted the overexpression of thermogenic genes induced by exogenous fatty acids, suggesting a regulatory role in energy dissipation pathways.
CONCLUSION
In conclusion, this study highlights ALA as a therapeutic agent in mitigating lipid accumulation and dysregulation in NAFLD.
Topics: Humans; Thioctic Acid; Hep G2 Cells; Lipid Metabolism; Non-alcoholic Fatty Liver Disease; Oleic Acid; Palmitic Acid; Gene Expression Regulation; Fatty Acids; PPAR gamma; Lipid Droplets; PPAR alpha; Uncoupling Protein 2
PubMed: 38940024
DOI: 10.31083/j.fbl2906209 -
Advances in Pharmacological and... 2024Nutritional supplements are gaining traction for their effects in mitigating the impacts of various health conditions. In particular, many supplements are being proposed...
Nutritional supplements are gaining traction for their effects in mitigating the impacts of various health conditions. In particular, many supplements are being proposed to reduce the impacts of type 2 diabetes (T2D), a metabolic condition that has reached global epidemic proportions. Recently, a supplement of oleic acid (OA) and succinic acid (SA; 1 : 1, w/w) was reported to improve glycaemic control in type 2 diabetic (T2D) Sprague-Dawley (S-D) rats through ameliorating insulin release and sensitivity. Here, we investigate the effects of the supplement (OA and SA) on hepatic and pancreatic function in T2D S-D rats. Eighteen (18) S-D rats were rendered diabetic and were divided into three equal groups: diabetic control, diabetic treatment, and diabetic glibenclamide. Another 12 S-D rats were obtained and served as the normal groups. The animals were treated daily with the vehicle, OA and SA (800 mg/kg body weight (bw); 1 : 1), or glibenclamide (10 mg/kg bw) which served as the positive control. The findings indicated that treatment with the supplement resulted in a 35.69 ± 4.22% reduction (=0.006) in blood glucose levels (BGL). Analysis of hepatic enzymes depicted that the nutritional supplement reduced the activity of the gluconeogenesis enzyme, glucose-6-phosphatase (G6P) while improved the activity of catabolic enzymes such as glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK). Furthermore, the supplement attenuated oxidative stress through restoration of catalase (CAT) and superoxide dismutase (SOD), while reducing malondialdehyde (MDA) levels. Finally, the supplement showed no liver or kidney toxicity and improved the size and number of pancreatic islets of Langerhans, indicating its potential application in treating T2D. The study highlighted that a supplement of the two organic acids may be beneficial in reducing the rate of pathogenesis of type 2 diabetes. Therefore, it may offer therapeutic value as a dietary or nutritional supplement in the approach against diabetes and its complications.
PubMed: 38938594
DOI: 10.1155/2024/5556722 -
AAPS PharmSciTech Jun 2024Our study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of β-sitosterol, a bioactive that is poorly...
Our study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of β-sitosterol, a bioactive that is poorly soluble in water. Here, we have taken advantage of the unique characteristics that cubosomes have to provide as a drug delivery system. These characteristics include a large surface area, thermal stability, and the capacity to encapsulate molecules that are hydrophobic, amphiphilic, and hydrophilic. The cubosomal formulation was optimized by building a central composite design. The optimum dispersion exhibited a particle size of 88.3 nm, a zeta potential of -43, a polydispersity index of 0.358, and drug entrapment of 95.6%. It was composed of 15% w/w oleic acid and 5% w/w pluronic F127. The optimized cubosome dispersion was incorporated into a sponge formulation. The optimized cubosome sponge achieved a higher drug release compared with the cubosome dispersion. The SEM micrograph of the selected sponge showed that it has an interwoven irregular fibrous lamellar structure with low density and high porosity. The in-vivo data revealed that topical application of the β-sitosterol cubosomal sponge showed significant higher wound closure percentage relative to the β-sitosterol product (Mebo)®.
Topics: Sitosterols; Animals; Chitosan; Drug Carriers; Particle Size; Burns; Drug Liberation; Wound Healing; Male; Drug Delivery Systems; Rats; Poloxamer; Hydrophobic and Hydrophilic Interactions; Nanostructures; Administration, Topical
PubMed: 38937387
DOI: 10.1208/s12249-024-02852-4 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2024Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent glocal cause of chronic hepatic disease, with incidence rates that continue to rise steadily....
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent glocal cause of chronic hepatic disease, with incidence rates that continue to rise steadily. Treatment options for affected patients are currently limited to dietary changes and exercise interventions, with no drugs having been licensed for the treatment of this disease. There is thus a pressing need for the development of novel therapeutic strategies. Work from our group suggests that the primary bioactive ingredient in green tea, epigallocatechin gallate (EGCG), may help reduce liver fat content and protect against hepatic injury through the inhibition of dipeptidyl peptidase 4 (DPP4) expression and activity. The study investigated the potential pathways by which EGCG may improve NAFLD, identified the sites of interaction between EGCG and DPP4, and proposed novel clinical treatment strategies.
METHODS
A clinical randomized controlled trial was conducted to investigate the potential efficacy of EGCG in NAFLD patients. The study compared relevant indices before and after EGCG administration. Animal models of NAFLD were constructed using male C57BL/6J mice fed a high-fat diet to observe the ameliorative effects of EGCG on the livers of the model mice and to investigate the potential pathways by which EGCG alleviates NAFLD. The interaction mechanism between EGCG and DPP4 was investigated using oleic acid and palmitic acid-treated HepG2 cell lines. Plasmids in which different sites had been disrupted were used to identify the effective interaction sites.
RESULTS
ECGC was found to suppress the accumulation of lipids, inhibit inflammation, remediate dysregulated lipid metabolism, and improve the pathogenesis of NAFLD via the inhibition of the expression and activity of DPP4.
CONCLUSIONS
The study results indicate that EGCG has a positive impact on improving NAFLD. These results highlight promising new opportunities to safely and effectively treat NAFLD in the clinic.
STUDY ID NUMBER
ChiCTR2300076741; https://www.chictr.org.cn/.
PubMed: 38936303
DOI: 10.1016/j.clnu.2024.06.018 -
MBio Jun 2024Contemporary antifungal therapies utilized to treat filamentous fungal infections are inhibited by intrinsic and emerging drug resistance. Consequently, there is an...
Contemporary antifungal therapies utilized to treat filamentous fungal infections are inhibited by intrinsic and emerging drug resistance. Consequently, there is an urgent need to develop novel antifungal compounds that are effective against drug-resistant filamentous fungi. Here, we utilized an cell-based high-throughput screen to identify small molecules with antifungal activity that also potentiated triazole activity. The screen identified 16 hits with promising activity against . A nonspirocyclic piperidine, herein named MBX-7591, exhibited synergy with triazole antifungal drugs and activity against pan-azole-resistant isolates. MBX-7591 has additional potent activity against species and CO-dependent activity against . Chemical, genetic, and biochemical mode of action analyses revealed that MBX-7591 increases cell membrane saturation by decreasing oleic acid content. MBX-7591 has low toxicity and shows good efficacy in decreasing fungal burden in a murine model of invasive pulmonary aspergillosis. Taken together, our results suggest MBX-7591 is a promising hit with a novel mode of action for further antifungal drug development to combat the rising incidence of triazole-resistant filamentous fungal infections.IMPORTANCEThe incidence of infections caused by fungi continues to increase with advances in medical therapies. Unfortunately, antifungal drug development has not kept pace with the incidence and importance of fungal infections, with only three major classes of antifungal drugs currently available for use in the clinic. Filamentous fungi, also called molds, are particularly recalcitrant to contemporary antifungal therapies. Here, a recently developed cell reporter strain was utilized to conduct a high-throughput screen to identify small molecules with antifungal activity. An emphasis was placed on small molecules that potentiated the activity of contemporary triazole antifungals and led to the discovery of MBX-7591. MBX-7591 potentiates triazole activity against drug-resistant molds such as and has activity against Mucorales fungi. MBX-7591's mode of action involves inhibiting the conversion of saturated to unsaturated fatty acids, thereby impacting fungal membrane integrity. MBX-7591 is a novel small molecule with antifungal activity poised for lead development.
PubMed: 38934618
DOI: 10.1128/mbio.01166-24 -
Future Foods : a Dedicated Journal For... Jun 2024The prevailing global market demands locally produced, sustainable oils for biomedical applications. This study focused on evaluating the quality of cricket-derived oils...
The prevailing global market demands locally produced, sustainable oils for biomedical applications. This study focused on evaluating the quality of cricket-derived oils and meals from Hugel, Tanga, and De Geer common delicacy in Africa, following standard methods for physicochemical properties, fatty acid composition, and phytochemicals (oxalates, phytates, tannins, and polyphenols). The cricket oils physicochemical properties aligned with Codex Alimentarius standards for edible oils, including low solidification temperature (< 2 °C), a high refractive index (1.46), and a specific gravity of 0.88. Notably, peroxide values (1.9 to 2.5 mg mEq O2/kg), acid values (1.1 to 2.2 mg KOH/g), and saponification values (234-246 mg KOH/g) all are indicative of lightness and unsaturated fatty acids. Nutritionally, cricket powder was rich in protein (56.8-56.9% -) and fat (31.7-33.5% -of dry matter), with significant amounts of essential omega-3 and omega-6 fatty acids. Predominant saturated and monounsaturated fatty acids were palmitic (23.9-31.2 mg/100 g-) and oleic acids (10.9-11.4 mg/100 g- of oil), respectively. Antioxidant values (48.0 to 65.0 mg/100 g), inferred from total polyphenols, suggests a stable oil with long shelf-life. These results highlight the promising and sustainable potential of cricket-derived oils for applications in the food and pharmaceutical industries.
PubMed: 38932931
DOI: 10.1016/j.fufo.2024.100316 -
Polymers Jun 2024The antifungal agent, ketoconazole, and the anti-inflammatory drug, piroxicam, were incorporated into matrices of xanthan or oleic acid-esterified xanthan (Xn) and...
The antifungal agent, ketoconazole, and the anti-inflammatory drug, piroxicam, were incorporated into matrices of xanthan or oleic acid-esterified xanthan (Xn) and polyurethane (PU), to develop topical drug delivery systems. Compared to matrices without bioactive compounds, which only showed a nominal compressive stress of 32.18 kPa (sample xanthan-polyurethane) at a strain of 71.26%, the compressive resilience of the biomaterials increased to nearly 50.04 kPa (sample xanthan-polyurethane-ketoconazole) at a strain of 71.34%. The compressive strength decreased to around 30.67 kPa upon encapsulating a second drug within the xanthan-polyurethane framework (sample xanthan-polyurethane-piroxicam/ketoconazole), while the peak sustainable strain increased to 87.21%. The Weibull model provided the most suitable fit for the drug release kinetics. Unlike the materials based on xanthan-polyurethane, those made with oleic acid-esterified xanthan-polyurethane released the active ingredients more slowly (the release rate constant showed lower values). All the materials demonstrated antimicrobial effectiveness. Furthermore, a higher volume of piroxicam was released from oleic acid-esterified xanthan-polyurethane-piroxicam (64%) as compared to xanthan-polyurethane-piroxicam (44%). Considering these results, materials that include polyurethane and either modified or unmodified xanthan showed promise as topical drug delivery systems for releasing piroxicam and ketoconazole.
PubMed: 38932084
DOI: 10.3390/polym16121734 -
Pharmaceuticals (Basel, Switzerland) Jun 2024This study explores developing and optimizing a nanoemulsion (NE) system loaded with dipyridamole and roflumilast, aiming to improve skin penetration and retention. The...
Development and Optimization of Dipyridamole- and Roflumilast-Loaded Nanoemulsion and Nanoemulgel for Enhanced Skin Permeation: Formulation, Characterization, and In Vitro Assessment.
This study explores developing and optimizing a nanoemulsion (NE) system loaded with dipyridamole and roflumilast, aiming to improve skin penetration and retention. The NE formulation was further transformed into a nanoemulgel to enhance its application as a topical treatment for psoriasis. Solubility studies were conducted to select the oil, surfactant, and co-surfactant. Phase diagrams were constructed using the aqueous phase titration method. All the formulations were in nanoscale, and Formula (F2) (which contains oleic acid oil as the oil phase, a mixture of Surfactant Tween 80 and co-surfactant (ethanol) at a ratio of 1:2 in addition to distilled water as an aqueous phase in a ratio of 1:5:4, respectively) was the selected formula depending on the particle size, PDI, and zeta potential. Formula (F2) has the best ratio because it gives the smallest nanoemulsion globule size (particle size average of 167.1 nm), the best homogenicity (lowest PDI of 0.195), and the highest stability (higher zeta potential of -32.22). The selected formula was converted into a nanoemulgel by the addition of 0.5% (/) xanthan gum (average particle size of 172.7 nm) and the best homogenicity (lowest PDI of 0.121%) and highest stability (higher zeta potential of -28.31). In conclusion, the selected formula has accepted physical and chemical properties, which enhanced skin penetration.
PubMed: 38931470
DOI: 10.3390/ph17060803 -
Nutrients Jun 2024Psoriasis is a chronic systemic disease with a multifaceted pathomechanism and immunological basis, with the presence of inflammatory skin lesions and joint ailments....
Psoriasis is a chronic systemic disease with a multifaceted pathomechanism and immunological basis, with the presence of inflammatory skin lesions and joint ailments. Diseases accompanying psoriasis include metabolic and cardiovascular disorders. It has been suggested that inflammation is involved in the development of each of these conditions. The main objective of this study was to analyse the fatty acid profile, including polyunsaturated fatty acids, in the erythrocyte membranes of patients suffering from psoriasis. A total of 58 adult patients of the Department of Skin and Venereal Diseases of the Pomeranian Medical University in Szczecin, suffering from psoriasis, were qualified for this study. The patients had undergone an interview and physical examination, during which the severity of psoriasis was assessed. All patients had their weight and height measured to assess their body mass index (BMI). After 3 months of treatment, biochemical parameters (ALT, AST, total cholesterol) and inflammatory markers (CRP) in the blood were assessed. In addition, the isolation of fatty acids (PUFAs, SFAs, MUFAs) from erythrocyte membranes and the qualitative and quantitative analysis of their profile using a gas chromatograph were carried out. In patients with severe psoriasis requiring systemic treatment, an altered profile of fatty acids in erythrocyte membranes was found, including a significantly lower concentration of polyunsaturated fatty acids (omega-3), which have an anti-inflammatory effect; a significantly higher concentration of saturated fatty acids; and a decreased concentration of oleic acid (omega-9), compared to the results obtained in patients with less severe psoriasis receiving topical treatment. In patients with psoriasis and BMI ≥ 25, significantly higher concentrations of AST and ALT in the blood and significantly higher concentrations of pro-inflammatory arachidonic acid in erythrocyte membranes were found. Elevated concentrations of saturated (R = 0.31) and monounsaturated fatty acids (R = 0.29) may correlate with a greater severity of psoriasis.
Topics: Humans; Psoriasis; Erythrocyte Membrane; Female; Male; Middle Aged; Fatty Acids; Adult; Body Mass Index; Fatty Acids, Unsaturated; Severity of Illness Index; Biomarkers; Aged
PubMed: 38931154
DOI: 10.3390/nu16121799 -
Plants (Basel, Switzerland) Jun 2024Lemon essential oil, derived from , possesses diverse health-promoting properties, including antioxidant, antimicrobial, and mood-enhancing effects. Despite its...
Lemon essential oil, derived from , possesses diverse health-promoting properties, including antioxidant, antimicrobial, and mood-enhancing effects. Despite its traditional use in aromatherapy and complementary medicine, there is a need for comprehensive investigations into its therapeutic potential, particularly in mitigating DNA damage and supporting health in palliative care settings. This study aimed to evaluate the antigenotoxic effects of lemon essential oil in human peripheral blood mononuclear cells and to explore its potential applications in palliative care. Treatment with lemon essential oil significantly reduced DNA damage, with 1% w/v with 3.13% DNA in tail demonstrating greater efficacy. Furthermore, lemon essential oil attenuated streptonigrin-induced DNA damage, suggesting a potential protective effect against oxidative stress, especially at 3% w/v, with 11.81% DNA in tail. Compared to olive oil treatment, the DNA damage was significantly lower with streptonigrin treatment alone, which had 47.06% DNA in tail, while the olive oil treatment resulted in 36.88% DNA in tail. These results can be attributed to the main constituents: limonene in lemon essential oil and oleic acid in olive oil. These results suggest a potential role in mitigating oxidative stress and supporting genomic stability. Further research is warranted to elucidate the mechanisms of action and clinical applications in palliative care.
PubMed: 38931055
DOI: 10.3390/plants13121623