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Food Chemistry Oct 2024Oleogels are innovative structured fat systems that can replace detrimental lipids and saturated fats. Among the various gelators used to construct oleogels,... (Review)
Review
Oleogels are innovative structured fat systems that can replace detrimental lipids and saturated fats. Among the various gelators used to construct oleogels, phytosterols are regarded as potential oleogelators due to ability to lower blood cholesterol levels and protect patients from cardiovascular illnesses, although little research has been conducted on phytosterols. This article examines the formation, characterization, and application of phytosterol-based oleogels in detail. The oleogelation behaviors of phytosterol-based oleogels are affected by their formulation, which includes phytosterol type, combined oleogelator, proportion, concentration and oil type. These oleogels exhibit potential applications as solid fat substitutes without affecting the texture or sensory properties of food products or as effective delivery vehicles. To encourage the research and implementation of phytosterol-based oleogels, we will ultimately not only highlight problems related to their use in food processing, but also provide a few viewpoints, with the goal of providing fresh insights for advancing trends.
Topics: Phytosterols; Organic Chemicals; Humans; Fat Substitutes
PubMed: 38815329
DOI: 10.1016/j.foodchem.2024.139821 -
Chemistry & Biodiversity May 2024Cold-pressed Camelina oil is a traditional oil registered as a traditional food in Poland. Camelina oil has health-promoting properties and high oxidative stability....
Cold-pressed Camelina oil is a traditional oil registered as a traditional food in Poland. Camelina oil has health-promoting properties and high oxidative stability. This may be due to the presence of various bioactive antioxidant compounds such as carotenoids, sterols and polyphenols. Bioactive compounds content in Camelina oil depends mainly on the varieties and on the conditions under which the crop was grown therefore the aim of the research was to analyse antioxidant bioactive compounds in oil from different cultivars of Camelina sativa seeds and to determine their relationship with oil parameters.
PubMed: 38814629
DOI: 10.1002/cbdv.202400523 -
Human Cell Jul 2024To explore the effects of β-Sitosterol upon hepatocellular carcinoma cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT),...
To explore the effects of β-Sitosterol upon hepatocellular carcinoma cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT), and to investigate the underlying mechanism using network pharmacology. Human hepatocellular carcinoma cell lines (Huh-7 and HCCLM3) were expose to gradient concentrations of β-Sitosterol (5 μg/mL, 10 μg/mL, and 20 μg/mL). Cell viability and proliferation were assessed using MTT, CCK-8, colony formation, and EdU assays.Flow cytometry was employed to evaluate cell cycle and apoptosis. Scratch and Transwell assays were performed, respectively, to detect cell migration and invasion. The levels of apoptosis-associated proteins (BAX, BCL2, and cleaved caspase3) as well as EMT-associated proteins (E-cadherin, N-cadherin, Snail, and Vimentin) were detected in Huh-7 and HCCLM3 cell lines using Western blot analysis. The drug target gene for β-Sitosterol was screened via PubChem and subsequently evaluated for expression in the GSE112790 dataset. In addition, the expression level of glycogen synthase kinase 3 beta (GSK3B) within the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database was analyzed, along with its correlation to the survival outcomes of patients with hepatocellular carcinoma. The diagnostic efficiency of GSK3B was assessed by analyzing the ROC curve. Subsequently, Huh-7 and HCCLM3 cell lines were transfected with the overexpression vector of GSK3B and then treated with β-Sitosterol to further validate the association between GSK3B and β-Sitosterol. GSK3B demonstrated a significantly elevated expression in patients with hepatocellular carcinoma, which could predict hepatocellular carcinoma patients' impaired prognosis based on GEO dataset and TCGA database. GSK3B inhibitor (CHIR-98014) notably inhibited cell proliferation and invasion, promoted cell apoptosis and cell cycle arrest at G0/G1 phase in hepatocellular carcinoma cells. β-Sitosterol treatment further promoted the efffects of GSK3B inhibitor on hepatocellular carcinoma cells. GSK3B overexpression has been found to enhance the proliferative and invasive capabilities of hepatocellular carcinoma cells. Furthermore it has been observed that GSK3B overexpression, it has been obsear can partially reverse the inhibitory effect of β-Sitosterol upon hepatocellular. β-Sitosterol suppressed hepatocellular carcinoma cell proliferation and invasion, and enhanced apoptosis via inhibiting GSK3B expression.
Topics: Humans; Sitosterols; Glycogen Synthase Kinase 3 beta; Carcinoma, Hepatocellular; Liver Neoplasms; Cell Proliferation; Apoptosis; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Cell Movement; Gene Expression; Phenotype; Neoplasm Invasiveness; Cell Survival; Network Pharmacology; Gene Expression Regulation, Neoplastic
PubMed: 38814517
DOI: 10.1007/s13577-024-01081-y -
Inflammopharmacology May 2024Osteoarthritis (OA) is one of the leading causes of joint dysfunction and disability in the elderly, posing serious social problems and a huge socio-economic burden.... (Review)
Review
Osteoarthritis (OA) is one of the leading causes of joint dysfunction and disability in the elderly, posing serious social problems and a huge socio-economic burden. Existing pharmacological treatments have significant drawbacks, and searching for an effective pharmacological intervention is an urgent priority. Recent studies have demonstrated the chondroprotective, anabolic, and anti-catabolic properties of avocado-soybean unsaponifiable (ASU), a natural plant extract made from avocado and soybean oils, consisting of the remainder of the saponified portion of the product that cannot be made into soap. The main components of ASU are phytosterols, beta-sitosterol, canola stanols, and soya stanols, which are rapidly incorporated into cells. Studies have confirmed the anti-inflammatory, antioxidant, and analgesic properties of phytosterols. ASU slows down the progression of OA primarily by inhibiting pathways involved in the development of OA disease. ASU prevents cartilage degradation by inhibiting the release and activity of matrix metalloproteinases and by increasing the tissue inhibition of these catabolic enzymes; ASU is also involved in the inhibition of the activation of nuclear factor κB (NF-κB) which is a transcriptional inhibitor that regulates the inflammatory response of chondrocytes. NF-κB is a transcription factor that regulates the inflammatory response of chondrocytes, and inhibition of the transfer of the transcription factor NF-κB from the cytoplasm to the nucleus regulates the transcription of many pro-inflammatory factors. By appealing to the mechanism of action and thus achieving anti-inflammatory, anti-catabolic, and pro-synthetic effects on cartilage tissues, AUS is clinically responsive to the reduction of acute pain and OA symptom progression. This paper aims to summarize the studies on the use of avocado-soybean unsaponifiable in the pharmacological treatment of osteoarticular.
PubMed: 38814416
DOI: 10.1007/s10787-024-01496-x -
Food & Function Jun 2024Babassu coconut ( syn. ) contains an oil-rich nut and is primarily found in South America's Amazon region. Future market researchers predict an increase in the babassu... (Review)
Review
Babassu coconut ( syn. ) contains an oil-rich nut and is primarily found in South America's Amazon region. Future market researchers predict an increase in the babassu oil market from USD 227.7 million in 2022 to USD 347.0 million by 2032, and the yield of babassu oil from babassu-processed waste could reach 90%. Of these, mesocarp flour is an underrated by-product used only for animal feed purposes by local producers. This comprehensive review focuses on advances in knowledge and understanding of phytochemicals from babassu oil by-products considering the mechanisms of action - covering antioxidant, antimicrobial, antiparasitic, anti-inflammatory, antithrombotic, immunomodulatory, and anticancer effects. Babassu coconut fruit contains free fatty acids, (poly)phenols, phytosterols, and triterpenes. Pytochemicals, antiparasitic and antibacterial activities of babassu mesocarp flour were shown, but fungi and viruses can get more attention. Beyond its antioxidant capacity, babassu mesocarp flour showed potential as a dietary food supplement. Aqueous suspensions of mesocarp flour with a higher preference for cancer cells than normal cells and an antithrombotic effect were also identified, probably related to the antioxidant capacity of its secondary metabolites. Mesocarp flour, a starch-rich fraction, is promising for application as biodegradable packaging to improve the oxidative stability of foods. Finally, low-added value fractions can be considered bio-waste/co-products, and their phytochemicals may attract interest for applications in medicine and nutrition. Toxicological concerns, trends, and gaps are discussed for the future of foods and related sciences.
Topics: Humans; Dietary Supplements; Plant Oils; Antioxidants; Phytochemicals; Animals; Waste Products
PubMed: 38814112
DOI: 10.1039/d4fo01594k -
Research (Washington, D.C.) 20244,4-Dimethylsterols constitute a unique class of phytosterols responsible for regulating endogenous cannabinoid system (ECS) functions. However, precise mechanism...
4,4-Dimethylsterols constitute a unique class of phytosterols responsible for regulating endogenous cannabinoid system (ECS) functions. However, precise mechanism through which 4,4-dimethylsterols affect fat metabolism and the linkage to the ECS remain unresolved. In this study, we identified that 4,4-dimethylsterols, distinct from 4-demethseterols, act as inhibitors of fatty acid amide hydrolases (FAAHs) both in vivo and in vitro. Genetic ablation of FAAHs () abolishes the effects of 4,4-dimethylsterols on fat accumulation and locomotion behavior in a model. We confirmed that dietary intervention with 4,4-dimethylsterols in a high-fat diet (HFD) mouse model leads to a significant reduction in body weight (>11.28%) with improved lipid profiles in the liver and adipose tissues and increased fecal triacylglycerol excretion. Untargeted and targeted metabolomics further verified that 4,4-dimethylsterols influence unsaturated fatty acid biosynthesis and elevate oleoyl ethanolamine levels in the intestine. We propose a potential molecular mechanism in which 4,4-dimethylsterols engage in binding interactions with the catalytic pocket (Ser241) of FAAH-1 protein due to the shielded polarity, arising from the presence of 2 additional methyl groups (CH). Consequently, 4,4-dimethylsterols represent an unexplored class of beneficial phytosterols that coordinate with FAAH-1 activity to reduce fat accumulation, which offers new insight into intervention strategies for treating diet-induced obesity.
PubMed: 38812531
DOI: 10.34133/research.0377 -
Food & Function Jun 2024This study investigates the gut anti-inflammatory activity of a plant sterol (PS) food supplement (PS-FS), alongside PS-enriched milk-based fruit beverage and...
This study investigates the gut anti-inflammatory activity of a plant sterol (PS) food supplement (PS-FS), alongside PS-enriched milk-based fruit beverage and PS-enriched rye bread. A co-culture model based on a dual-chamber system with differentiated intestinal-like Caco-2 cells (apical) and RAW264.7 macrophages (basolateral) was used. The bioaccessible fractions (BF) of the samples were obtained after INFOGEST 2.0 simulated gastrointestinal digestion. The BF were added to the apical part (diluted 1/20 v/v with culture medium to avoid cytotoxicity) for 90 min, followed by stimulation with lipopolysaccharide (LPS) (1 μg mL, 24 h) on the basolateral side. The pharmacological interaction between samples and budesonide (1 μM, 90 min) was evaluated. Results indicate that PS-FS significantly attenuated LPS-induced secretion of IL-8 (28%) by Caco-2 cells, and TNF-α (9%) and IL-6 (54%) by RAW264.7 macrophages, whereas PS-enriched beverage and bread did not exhibit protective effects. Additionally, PS-FS demonstrated an improvement in oxidative status in Caco-2 cells, evidenced by reduced levels of reactive oxygen species (47%), iNOS protein expression (27%), and nitrite/nitrate secretion (27%). Mechanistically, PS-FS inhibited the NF-κB-COX-2-PGE signaling pathway in macrophages, resulting in decreased NF-κB p65 nuclear translocation (39%), COX-2 protein expression (32%), and PGE production (27%). Co-treatment with budesonide and PS-FS displayed an antagonistic effect (combination index 0.38-0.63). This study demonstrates the potent intestinal anti-inflammatory activity of a PS-FS, positioning it as a promising nutraceutical product for the management of inflammatory bowel diseases. However, the food matrix of the milk-based fruit beverage and rye bread appear to interfere with the anti-inflammatory activity of PS.
Topics: Humans; Caco-2 Cells; Anti-Inflammatory Agents; Animals; Mice; Phytosterols; Coculture Techniques; RAW 264.7 Cells; Macrophages; Inflammation; Dietary Supplements; Interleukin-6; Tumor Necrosis Factor-alpha; NF-kappa B; Interleukin-8; Lipopolysaccharides
PubMed: 38804902
DOI: 10.1039/d4fo00917g -
Current Cancer Drug Targets 2024The energy supply of certain cancer cells depends on aerobic glycolysis rather than oxidative phosphorylation. Our previous studies have shown that withaferin A (WA), a...
BACKGROUND
The energy supply of certain cancer cells depends on aerobic glycolysis rather than oxidative phosphorylation. Our previous studies have shown that withaferin A (WA), a lactone compound derived from , suppresses skin carcinogenesis at least partially by stabilizing IDH1 and promoting oxidative phosphorylation. Here, we have extended our studies to evaluate the anti-tumor effect of WA in liver cancer.
METHODS
Differential expression of glycolysis-related genes between liver cancer tissues and normal tissues and prognosis were verified using an online database. Glycolysis-related protein expression was detected using western blot after overexpression and knockdown of IDH1 and mitochondrial membrane potential assay based on JC-1, and mitochondrial complex I activity was also detected. The inhibitory effect of WA on the biological functions of HepG2 cells was detected along with cell viability using MTT assay, scratch assay, clone formation assay, glucose consumption and lactate production assay. Western blot and qRT-PCR were used to detect the expression of proteins and genes related to IDH1, p53 and HIF1α signaling pathways.
RESULTS
We first identified that IDH1 expression was downregulated in human liver cancer cells compared to normal liver cells. Next, we found that treatment of HepG2 cells with WA resulted in significantly increased protein levels of IDH1, accompanied by decreased levels of several glycolytic enzymes. Furthermore, we found that WA stabilized IDH1 proteins by inhibiting the degradation by the proteasome. The tumor suppressor p53 was also upregulated by WA treatment, which played a critical role in the upregulation of IDH1 and downregulation of the glycolysis-related genes. Under hypoxic conditions, glycolysis-related genes were induced, which was suppressed by WA treatment, and IDH1 expression was still maintained at higher levels under hypoxia.
CONCLUSION
Taken together, our results indicated that WA suppresses liver cancer tumorigenesis by p53-mediated IDH1 upregulation, which promotes mitochondrial respiration, thereby inhibiting the HIF-1α pathway and blocking aerobic glycolysis.
Topics: Humans; Withanolides; Tumor Suppressor Protein p53; Hypoxia-Inducible Factor 1, alpha Subunit; Glycolysis; Liver Neoplasms; Signal Transduction; Isocitrate Dehydrogenase; Cell Proliferation; Hep G2 Cells; Gene Expression Regulation, Neoplastic; Carcinogenesis
PubMed: 38804345
DOI: 10.2174/0115680096262915231026050602 -
World Journal of Microbiology &... May 2024Withanolides are steroidal lactones with diverse bioactive potential and their production from plant sources varies with genotype, age, culture conditions, and...
Withanolides are steroidal lactones with diverse bioactive potential and their production from plant sources varies with genotype, age, culture conditions, and geographical region. Endophytic fungi serve as an alternative source to produce withanolides, like their host plant, Withania somnifera (L.) Dunal. The present study aimed to isolate endophytic fungi capable of producing withanolides, characterization and investigation of biological activities of these molecules. The methanolic fungal crude extract of one of the fungal isolates WSE16 showed maximum withanolide production (219 mg/L). The fungal isolate WSE16 was identified as Penicillium oxalicum based on its morphological and internal transcribed spacer (ITS) sequence analysis and submitted in NCBI (accession number OR888725). The methanolic crude extract of P. oxalicum was further purified by column chromatography, and collected fractions were assessed for the presence of withanolides. Fractions F3 and F4 showed a higher content of withanolides (51.8 and 59.1 mg/L, respectively) than other fractions. Fractions F3 and F4 exhibited antibacterial activity against Staphylococcus aureus with an IC of 23.52 and 17.39 µg/ml, respectively. These fractions also showed antioxidant activity (DPPH assay with IC of 39.42 and 38.71 µg/ml, superoxide anion scavenging assay with IC of 41.10 and 38.84 µg/ml, and reducing power assay with IC of 42.61 and 41.40 µg/ml, respectively) and acetylcholinesterase inhibitory activity (IC of 30.34 and 22.05 µg/ml, respectively). The withanolides present in fraction 3 and fraction 4 were identified as (20S, 22R)-1a-Acetoxy-27-hydroxywitha-5, 24-dienolide-3b-(O-b-D-glucopyranoside) and withanamide A, respectively, using UV, FTIR, HRMS, and NMR analysis. These results suggest that P. oxalicum, an endophytic fungus isolated from W. somnifera, is a potential source for producing bioactive withanolides.
Topics: Withania; Withanolides; Penicillium; Endophytes; Antioxidants; Anti-Bacterial Agents; Phylogeny; Cholinesterase Inhibitors; Microbial Sensitivity Tests
PubMed: 38802663
DOI: 10.1007/s11274-024-04017-8 -
Scientific Reports May 2024Estrogen receptor-negative [ER(-)] mammary cancer is the most aggressive type of breast cancer (BC) with higher rate of metastasis and recurrence. In recent years,...
A novel combinatorial approach using sulforaphane- and withaferin A-rich extracts for prevention of estrogen receptor-negative breast cancer through epigenetic and gut microbial mechanisms.
Estrogen receptor-negative [ER(-)] mammary cancer is the most aggressive type of breast cancer (BC) with higher rate of metastasis and recurrence. In recent years, dietary prevention of BC with epigenetically active phytochemicals has received increased attention due to its feasibility, effectiveness, and ease of implementation. In this regard, combinatorial phytochemical intervention enables more efficacious BC inhibition by simultaneously targeting multiple tumorigenic pathways. We, therefore, focused on investigation of the effect of sulforaphane (SFN)-rich broccoli sprouts (BSp) and withaferin A (WA)-rich Ashwagandha (Ash) combination on BC prevention in estrogen receptor-negative [ER(-)] mammary cancer using transgenic mice. Our results indicated that combinatorial BSp + Ash treatment significantly reduced tumor incidence and tumor growth (~ 75%) as well as delayed (~ 21%) tumor latency when compared to the control treatment and combinatorial BSp + Ash treatment was statistically more effective in suppressing BC compared to single BSp or Ash intervention. At the molecular level, the BSp and Ash combination upregulated tumor suppressors (p53, p57) along with apoptosis associated proteins (BAX, PUMA) and BAX:BCL-2 ratio. Furthermore, our result indicated an expressional decline of epigenetic machinery HDAC1 and DNMT3A in mammary tumor tissue because of combinatorial treatment. Interestingly, we have reported multiple synergistic interactions between BSp and Ash that have impacted both tumor phenotype and molecular expression due to combinatorial BSp and Ash treatment. Our RNA-seq analysis results also demonstrated a transcriptome-wide expressional reshuffling of genes associated with multiple cell-signaling pathways, transcription factor activity and epigenetic regulations due to combined BSp and Ash administration. In addition, we discovered an alteration of gut microbial composition change because of combinatorial treatment. Overall, combinatorial BSp and Ash supplementation can prevent ER(-) BC through enhanced tumor suppression, apoptosis induction and transcriptome-wide reshuffling of gene expression possibly influencing multiple cell signaling pathways, epigenetic regulation and reshaping gut microbiota.
Topics: Isothiocyanates; Animals; Withanolides; Sulfoxides; Female; Mice; Epigenesis, Genetic; Breast Neoplasms; Gastrointestinal Microbiome; Mice, Transgenic; Plant Extracts; Receptors, Estrogen; Humans; Brassica; Histone Deacetylase 1; Gene Expression Regulation, Neoplastic; Anticarcinogenic Agents
PubMed: 38802425
DOI: 10.1038/s41598-024-62084-1