Genome-wide association study and meta-analysis of phytosterols identifies a novel locus for serum levels of campesterol.

Sitosterolemia is a rare inherited disorder caused by mutations in the ABCG5/ABCG8 genes. These genes encode proteins involved in the transport of plant sterols. Mutations in these genes lead to decreased excretion of phytosterols, which can accumulate in the body and lead to a variety of health problems, including premature coronary artery disease. We conducted the first genome-wide association study (GWAS) in the Middle East/North Africa population to identify genetic determinants of plant sterol levels in Qatari people. GWAS was performed on serum levels of ß-sitosterol and campesterol using the Metabolon platform from Qatar Biobank (QBB) and genome sequence data provided by Qatar Genome Program. A trans-ancestry meta-analysis of data from our Qatari cohort with summary statistics from a previously published large cohort (9758 subjects) of European ancestry was conducted. Using conditional analysis, we identified two independent single nucleotide polymorphisms associated with ß-sitosterol (rs145164937 and rs4299376), and two others with campesterol (rs7598542 and rs75901165) in the Qatari population in addition to previously reported variants. All of them map to the ABCG5/8 locus except rs75901165 which is located within the Intraflagellar Transport 43 (IFT43) gene. The meta-analysis replicated most of the reported variants, and our study provided significant support for the association of variants in SCARB1 and ABO with sitosterolemia. Evaluation of a polygenic risk score devised from European GWAS data showed moderate performance when applied to QBB (adjusted-R2 = 0.082). These findings provide new insights into the genetic architecture of phytosterol metabolism while showing the importance including under-represented populations in future GWAS studies.

A flavin-dependent monooxygenase produces nitrogenous tomato aroma volatiles using cysteine as a nitrogen source.

Tomato (Solanum lycopersicum) produces a wide range of volatile chemicals during fruit ripening, generating a distinct aroma and contributing to the overall flavor. Among these volatiles are several aromatic and aliphatic nitrogen-containing compounds for which the biosynthetic pathways are not known. While nitrogenous volatiles are abundant in tomato fruit, their content in fruits of the closely related species of the tomato clade is highly variable. For example, the green-fruited species Solanum pennellii are nearly devoid, while the red-fruited species S. lycopersicum and Solanum pimpinellifolium accumulate high amounts. Using an introgression population derived from S. pennellii, we identified a locus essential for the production of all the detectable nitrogenous volatiles in tomato fruit. Silencing of the underlying gene (SlTNH1;Solyc12g013690) in transgenic plants abolished production of aliphatic and aromatic nitrogenous volatiles in ripe fruit, and metabolomic analysis of these fruit revealed the accumulation of 2-isobutyl-tetrahydrothiazolidine-4-carboxylic acid, a known conjugate of cysteine and 3-methylbutanal. Biosynthetic incorporation of stable isotope-labeled precursors into 2-isobutylthiazole and 2-phenylacetonitrile confirmed that cysteine provides the nitrogen atom for all nitrogenous volatiles in tomato fruit. Nicotiana benthamiana plants expressing SlTNH1 readily transformed synthetic 2-substituted tetrahydrothiazolidine-4-carboxylic acid substrates into a mixture of the corresponding 2-substituted oxime, nitro, and nitrile volatiles. Distinct from other known flavin-dependent monooxygenase enzymes in plants, this tetrahydrothiazolidine-4-carboxylic acid N-hydroxylase catalyzes sequential hydroxylations. Elucidation of this pathway is a major step forward in understanding and ultimately improving tomato flavor quality.

ß-Sitosterol suppresses hepatocellular carcinoma growth and metastasis via FOXM1-regulated Wnt/ß-catenin pathway.

ß-Sitosterol is a natural compound with demonstrated anti-cancer properties against various cancers. However, its effects on hepatocellular carcinoma (HCC) and the underlying mechanisms are not well understood. This study aims to investigate the impact of ß-sitosterol on HCC. In this study, we investigated the effects of ß-sitosterol on HCC tumour growth and metastasis using a xenograft mouse model and a range of molecular analyses, including bioinformatics, real-time PCR, western blotting, lentivirus transfection, CCK8, scratch and transwell assays. The results found that ß-sitosterol significantly inhibits HepG2 cell proliferation, migration and invasion both in vitro and in vivo. Bioinformatics analysis identifies forkhead box M1 (FOXM1) as a potential target for ß-sitosterol in HCC treatment. FOXM1 is upregulated in HCC tissues and cell lines, correlating with poor prognosis in patients. ß-Sitosterol downregulates FOXM1 expression in vitro and in vivo. FOXM1 overexpression mitigates ß-sitosterol's inhibitory effects on HepG2 cells. Additionally, ß-sitosterol suppresses epithelial-mesenchymal transition (EMT) in HepG2 cells, while FOXM1 overexpression promotes EMT. Mechanistically, ß-sitosterol inhibits Wnt/ß-catenin signalling by downregulating FOXM1, regulating target gene transcription related to HepG2 cell proliferation and metastasis. ß-Sitosterol shows promising potential as a therapeutic candidate for inhibiting HCC growth and metastasis through FOXM1 downregulation and Wnt/ß-catenin signalling inhibition.

Poly(Sitosterol)-Based Hydrophobic Blocks in Amphiphilic Block Copolymers for the Assembly of Hybrid Vesicles.

Amphiphilic block copolymer and lipids can be assembled into hybrid vesicles (HVs), which are an alternative to liposomes and polymersomes. Block copolymers that have either poly(sitostryl methacrylate) or statistical copolymers of sitosteryl methacrylate and butyl methacrylate as the hydrophobic part and a poly(carboxyethyl acrylate) hydrophilic segment are synthesized and characterized. These block copolymers assemble into small HVs with soybean L-α-phosphatidylcholine (soyPC), confirmed by electron microscopy and small-angle X-ray scattering. The membrane's hybrid nature is illustrated by fluorescence resonance energy transfer between labeled building blocks. The membrane packing, derived from spectra when using Laurdan as an environmentally sensitive fluorescent probe, is comparable between small HVs and the corresponding liposomes with molecular sitosterol, although the former show indications of transmembrane asymmetry. Giant HVs with homogenous distribution of the block copolymers and soyPC in their membranes are assembled using the electroformation method. The lateral diffusion of both building blocks is slowed down in giant HVs with higher block copolymer content, but their permeability toward (6)-carboxy-X-rhodamine is higher compared to giant vesicles made of soyPC and molecular sitosterol. This fundamental effort contributes to the rapidly expanding understanding of the integration of natural membrane constituents with designed synthetic compounds to form hybrid membranes.

Daucosterol regulates JAK2-STAT3 signaling pathway to promote megakaryocyte differentiation.

Immune thrombocytopenia (ITP) is an autoimmune disease caused by the loss of immune tolerance to platelet autoantigens, resulting in reduced platelet production and increased platelet destruction. Impaired megakaryocyte differentiation and maturation is a key factor in the pathogenesis and treatment of ITP. Sarcandra glabra, a plant of the Chloranthaceae family, is commonly used in clinical practice to treat ITP, and daucosterol (Dau) is one of its active ingredients. However, whether Dau can treat ITP and the key mechanism of its effect are still unclear. In this study, we found that Dau could effectively promote the differentiation and maturation of megakaryocytes and the formation of polyploidy in the megakaryocyte differentiation disorder model constructed by co-culturing Dami and HS-5 cells. In vivo experiments showed that Dau could not only increase the number of polyploidized megakaryocytes in the ITP rat model, but also promote the recovery of platelet count. In addition, through network pharmacology analysis, we speculated that the JAK2-STAT3 signaling pathway might be involved in the process of Dau promoting megakaryocyte differentiation. Western blot results showed that Dau inhibited the expression of P-JAK2 and P-STAT3. In summary, these results provide a basis for further studying the pharmacological mechanism of Dau in treating ITP.

Short-term effects of gastric bypass versus sleeve gastrectomy on high LDL cholesterol: The BASALTO randomized clinical trial.

BACKGROUND: There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the superiority of Roux-en-Y gastric bypass (RYGB) for reducing low-density lipoprotein (LDL) cholesterol. The main aim was to ascertain whether high LDL cholesterol levels should be considered when selecting the most appropriate surgical procedure for each patient (RYGB or SG). METHODS: In this single-center, randomized clinical trial using intention-to-treat analysis, 38 patients with severe obesity and elevated levels of LDL cholesterol were randomly assigned to undergo RYGB or SG. The primary outcome was LDL cholesterol remission at 12 months, defined as LDL cholesterol < 3.36 nmol/l without lipid-lowering medications. Secondary outcomes included changes in weight, other comorbidities, qualitative lipoprotein traits, cholesterol esters, glycoproteins, cholesterol absorption and synthesis metabolites and complications. RESULTS: Intention-to-treat analysis revealed that LDL cholesterol remission occurred in 66.6% of RYGB patients compared to 27.8% of SG patients (p = 0.019). Among patients completing follow-up, RYGB demonstrated superior remission (80.0% vs. 29.4%, p = 0.005). Exclusive benefits of RYGB included a reduction in large, medium, and small LDL particles. Cholesterol absorption markers showed differential behavior after both techniques: campesterol (Δ -15.2 µg/mg, 95% CI -30.2 to -0.1) decreased after RYGB, and sitosterol (Δ 21.1 µg/mg, 95% CI 0.9 to 41.2), cholestanol (Δ 30.6 µg/mg, 95% CI 14.8 to 57.9) and campesterol (Δ 18.4 µg/mg, 95% CI 4.4 to 32.3) increased after SG. No differences in weight loss, cholesterol esters, glycoproteins, cholesterol synthesis metabolites or postoperative complications were observed between techniques. CONCLUSION: In conclusion, RYGB is superior to SG in terms of short-term of high LDL cholesterol remission. Furthermore, RYGB also led to a greater improvement in lipoprotein parameters that confer an atherogenic profile. Therefore, the presence of elevated levels of LDL cholesterol should be considered when determining the optimal bariatric surgery procedure for each patient. TRIAL REGISTRATION: Clinicaltrials.gov number, NCT03975478).

Alpha-sitosterol: a new antiviral agent produced by Streptomyces misakiensis and its potential activity against Newcastle disease virus.

BACKGROUND: Newcastle Disease Virus (NDV) causes severe economic losses in the poultry industry worldwide. Hence, this study aimed to discover a novel bioactive antiviral agent for controlling NDV. Streptomyces misakiensis was isolated from Egyptian soil and its secondary metabolites were identified using infrared spectroscopy (IR), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy. The inhibitory activity of bioactive metabolite against NDV were examined. Three experimental groups of 10-day-old specific pathogen-free embryonated chicken eggs (SPF-ECEs), including the bioactive metabolite control group, NDV control positive group, and α-sitosterol and NDV mixture-treated group were inoculated. RESULTS: α-sitosterol (Ethyl-6-methylheptan-2-yl]-10,13-dimethyl-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol), a secondary metabolite of S. misakiensis, completely inhibited hemagglutination (HA) activity of the NDV strain. The HA activity of the NDV strain was 8 log2 and 9 log2 for 0.5 and 0.75% RBCs, respectively. The NDV HA activity for the two concentrations of RBCs was significantly (P < 0.0001) inhibited after α-sitosterol treatment. There was a significant (P < 0.0001) decrease in the log 2 of HA activity, with values of - 0.500 (75%, chicken RBCs) before inoculation in SPF-ECEs and - 1.161 (50%, RBCs) and - 1.403 (75%, RBCs) following SPF-ECE inoculation. Compared to ECEs inoculated with NDV alone, the α-sitosterol-treated group showed improvement in histological lesion ratings for chorioallantoic membranes (CAM) and hepatic tissues. The CAM of the α-sitosterol- inoculated SPF-ECEs was preserved. The epithelial and stromal layers were noticeably thicker with extensive hemorrhages, clogged vasculatures, and certain inflammatory cells in the stroma layer in the NDV group. However, mild edema and inflammatory cell infiltration were observed in the CAM of the treated group. ECEs inoculated with α-sitosterol alone showed normal histology of the hepatic acini, central veins, and portal triads. Severe degenerative alterations, including steatosis, clogged sinusoids, and central veins, were observed in ECEs inoculated with NDV. Mild hepatic degenerative alterations, with perivascular round cell infiltration, were observed in the treated group. CONCLUSION: To the best of our knowledge, this is the first study to highlight that the potentially bioactive secondary metabolite, α-sitosterol, belonging to the terpene family, has the potential to be a biological weapon against virulent NDV. It could be used for the development of innovative antiviral drugs to control NDV after further clinical investigation.

Network pharmacology analysis and molecular docking using the Chinese herbal agent WYHX formula (according to Yan Dexin): Management of coronary artery disease.

BACKGROUND: The therapeutic impact of the Wenyang Huoxue (WYXH) formula on coronary atherosclerotic heart disease (CHD) is well established, yet the precise mechanisms are currently not fully understood. This study provides preliminary insights into the potential mechanisms underlying the therapeutic effects of the formula on CHD by utilizing network pharmacology and molecular docking technology. MATERIALS AND METHODS: The primary active constituents and their corresponding action targets for the formula were retrieved from the TCMSP database. Utilizing Cytoscape 3.9.1 software, a network linking the components of the formula to their respective targets was constructed. Information was collected from Genecards, OMIM, TTD, and DrugBank databases to identify targets related to CHD. The common targets shared by the formula and CHD were then imported into the STRING database to create a protein-protein interaction (PPI) network. Following this, enrichment analyses were performed on the shared targets using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, molecular docking was conducted on the primary active compounds and the core targets. RESULTS: The network encompassing the components and targets of the formula comprises a total of 311 nodes and 895 edges. Compounds exhibiting higher degree centrality consist of quercetin, ß-sitosterol, and kaempferol. In the PPI network, proteins with elevated degree centrality are protein kinase B (AKT1), epidermal growth factor receptor (EGFR), and mitogen-activated protein kinase 3 (MAPK3). The results of GO and KEGG enrichment analyses reveal that the biological processes associated with the efficacy of the formula in treating CHD primarily involve positive regulation of gene expression, hypoxia response, and lipopolysaccharide response, among others. The signaling pathways primarily involved include phosphatidylinositol 3-kinase and protein kinase B (PI3K-AKT), MAPK3, tumor necrosis factor (TNF), and so on. Molecular docking results demonstrate a strong affinity between quercetin, ß-sitosterol, and kaempferol with AKT1, EGFR, and MAPK3. CONCLUSION: We showed for the first time that AKT1, EGFR, and MAPK3 are potential targets influenced by the WYHX formula in CHD treatment. The therapeutic effects could possibly involve signaling pathways such as the PI3K-AKT, MAPK, TNF, and AGE-RAGE pathways.

Cerebral involvement in sitosterolemia.

BACKGROUND: Sitosterolemia, an autosomal recessive condition, is characterized by impaired metabolism of plant sterols. Clinical symptoms include skin xanthoma, premature atherosclerotic disease, arthritis, and unexplained hematological abnormalities. However, there is a dearth of studies on sitosterolemia-related brain damage. METHODS: This study focused on the family of two sitosterolemia patients who presented with severe hypercholesterolemia and xanthoma. Radiological examinations, biopsies, whole-exome sequencing (WES), and plant sterol tests were conducted. RESULTS: The index patient, a 66-year-old female, initially exhibited weakness in both lower limbs and later developed urinary and fecal incontinence. Neuroimaging showed that the falx of the brain had irregular fusiform thickening. Significant tissue edema was observed around the lesions in the bilateral frontal-parietal lobes. Pathological analysis of the biopsied brain lesion revealed extensive cholesterol crystal deposition and lymphocyte infiltration in the matrix. The index patient who experienced cerebral impairment and her sister both carried two compound heterozygous variants in ATP binding cassette transporter G5 (ABCG5). These included the nonsense variants NM_022436: c.751 C > T (p.Q251X) in exon 6 and NM_022436: c.1336 C > T (p.R446X) in exon 10. A notable increase in plant sterol levels was observed in the younger sister of the index patient. CONCLUSION: This study highlights a previously unreported neurological aspect of sitosterolemia. Imaging and pathology findings suggest that cholesterol crystals may be deposited in connective tissues such as the cerebral falx and pia mater through blood circulation.

Exploring the molecular mechanism of ginseng against anthracycline-induced cardiotoxicity based on network pharmacology, molecular docking and molecular dynamics simulation.

BACKGROUND: Previous clinical and basic studies have revealed that ginseng might have cardioprotective properties against anthracycline-induced cardiotoxicity (AIC). However, the underlying mechanism of ginseng action against AIC remains insufficiently understood. The aim of this study was to explore the related targets and pathways of ginseng against AIC using network pharmacology, molecular docking, cellular thermal shift assay (CETSA) and molecular dynamics (MD) simulations. RESULTS: Fourteen drug-disease common targets were identified. Enrichment analysis showed that the AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathway were potentially involved in the action of ginseng against AIC. Molecular docking demonstrated that the core components including Kaempferol, beta-Sitosterol, and Fumarine had notable binding activity with the three core targets CCNA2, STAT1, and ICAM1. Furthermore, the stable complex of STAT1 and Kaempferol with favorable affinity was further confirmed by CETSA and MD simulation. CONCLUSIONS: This study suggested that ginseng might exert their protective effects against AIC through the derived effector compounds beta-Sitosterol, Kaempferol and Fumarine by targeting CCNA2, STAT1, and ICAM1, and modulating AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathways.

A network pharmacology- and transcriptomics-based investigation reveals an inhibitory role of ß-sitosterol in glioma via the EGFR/MAPK signaling pathway.

Glioma is characterized by rapid cell proliferation, aggressive invasion, altered apoptosis and a poor prognosis. ß-Sitosterol, a kind of phytosterol, has been shown to possess anticancer activities. Our current study aims to investigate the effects of ß-sitosterol on gliomas and reveal the underlying mechanisms. Our results show that ß-sitosterol effectively inhibits the growth of U87 cells by inhibiting proliferation and inducing G2/M phase arrest and apoptosis. In addition, ß-sitosterol inhibits migration by downregulating markers of epithelial-mesenchymal transition (EMT). Mechanistically, network pharmacology and transcriptomics approaches illustrate that the EGFR/MAPK signaling pathway may be responsible for the inhibitory effect of ß-sitosterol on glioma. Afterward, the results show that ß-sitosterol effectively suppresses the EGFR/MAPK signaling pathway. Moreover, ß-sitosterol significantly inhibits tumor growth in a U87 xenograft nude mouse model. ß-Sitosterol inhibits U87 cell proliferation and migration and induces apoptosis and cell cycle arrest in U87 cells by blocking the EGFR/MAPK signaling pathway. These results suggest that ß-sitosterol may be a promising therapeutic agent for the treatment of glioma.

Transcriptomic analysis reveals the inhibitory effect of beta-sitosterol on proliferation of bovine preadipocytes.

Fat deposition affects beef quantity and quality via preadipocyte proliferation. Beta-sitosterol, a natural small molecular compound, has various functions, such as anti-inflammation, antibacterial, and anticancer properties. The mechanism of action of Beta-sitosterol on bovine preadipocytes remains unclear. This study, based on RNA-seq, reveals the impact of Beta -sitosterol on the proliferation of bovine preadipocytes. Compared to the control group, Beta-sitosterol demonstrated a more pronounced inhibitory effect on cell proliferation after 48 hours of treatment than after 24 hours, as evidenced by the results of EdU staining and flow cytometry. RNA-seq and Western Blot analyses further substantiated these findings. Our results suggest that the impact of Beta-sitosterol on the proliferation of bovine preadipocytes is not significant after a 24-hour treatment. It is only after extending the treatment time to 48 hours that Beta-sitosterol may induce cell cycle arrest at the G2/M phase by suppressing the expression of CCNB1, thereby inhibiting the proliferation of bovine preadipocytes.

Anticancer activity and other biomedical properties of ß-sitosterol: Bridging phytochemistry and current pharmacological evidence for future translational approaches.

Sterols, including ß-sitosterol, are essential components of cellular membranes in both plant and animal cells. Despite being a major phytosterol in various plant materials, comprehensive scientific knowledge regarding the properties of ß-sitosterol and its potential applications is essential for scholarly pursuits and utilization purposes. ß-sitosterol shares similar chemical characteristics with cholesterol and exhibits several pharmacological activities without major toxicity. This study aims to bridge the gap between phytochemistry and current pharmacological evidence of ß-sitosterol, focusing on its anticancer activity and other biomedical properties. The goal is to provide a comprehensive understanding of ß-sitosterol's potential for future translational approaches. A thorough examination of the literature was conducted to gather relevant information on the biological properties of ß-sitosterol, particularly its anticancer therapeutic potential. Various databases were searched, including PubMed/MedLine, Scopus, Google Scholar, and Web of Science using appropriate keywords. Studies investigating the effects of ß-sitosterol on different types of cancer were analyzed, focusing on mechanisms of action, pharmacological screening, and chemosensitizing properties. Modern pharmacological screening studies have revealed the potential anticancer therapeutic properties of ß-sitosterol against various types of cancer, including leukemia, lung, stomach, breast, colon, ovarian, and prostate cancer. ß-sitosterol has demonstrated chemosensitizing effects on cancer cells, interfering with multiple cell signaling pathways involved in proliferation, cell cycle arrest, apoptosis, survival, metastasis invasion, angiogenesis, and inflammation. Structural derivatives of ß-sitosterol have also shown anti-cancer effects. However, research in the field of drug delivery and the detailed mode of action of ß-sitosterol-mediated anticancer activities remains limited. ß-sitosterol, as a non-toxic compound with significant pharmacological potential, exhibits promising anticancer effects against various cancer types. Despite being relatively less potent than conventional cancer chemotherapeutics, ß-sitosterol holds potential as a safe and effective nutraceutical against cancer. Further comprehensive studies are recommended to explore the biological properties of ß-sitosterol, including its mode of action, and develop novel formulations for its potential use in cancer treatment. This review provides a foundation for future investigations and highlights the need for further research on ß-sitosterol as a potent superfood in combating cancer.

Evaluation of bone contact area and intercondylar distance changes in orthognathic surgery - a comparison between BSSO and HSSO technique depending on mandibular displacement extent.

OBJECTIVES: The present study aims to assess the impact of bilateral and high oblique sagittal split osteotomy (BSSO/HSSO), as well as displacement distances and directions on the expected and achievable bone contact area (BCA) and changes in the intercondylar distance (ICD). The primary question addressed is whether mandibular splitting through BSSO results in a greater BCA and/or ICD when compared to splitting through HSSO. MATERIALS AND METHODS: Totally 80 mandibular displacements were performed on 20 fresh cadavers, for each subject, four splints were produces to facilitate mandibular advancement as well as setbacks of 4 and 8 mm. Pre- and postoperative CBCT scans were performed to plan the surgical procedures and to analyze the expected and achieved BCA and ICD. RESULTS: Regarding the maximum mandibular displacement, the expected BCA for HSSO/BSSO were 352.58 ± 96.55mm2 and 1164.00 ± 295.50mm2, respectively, after advancement and 349.11 ± 98.42mm2 and 1344.70 ± 287.23mm2, respectively, after setback. The achieved BCA for HSSO/BSSO were 229.37 ± 75.90mm2 and 391.38 ± 189.01mm2, respectively, after advancement and 278.03 ± 97.65mm2 and 413.52 ± 169.52 mm2, respectively after setback. The expected ICD for HSSO/BSSO were 4.51 ± 0.73 mm and 3.25 ± 1.17 mm after advancement and - 5.76 ± 1.07 mm and - 4.28 ± 1.58 mm after setback. The achieved ICD for HSSO/BSSO were 2.07 ± 2.9 mm and 1.7 ± 0.60 mm after advancement and - 2.57 ± 2.78 mm and - 1.28 ± 0.84 mm after setback. Significant differences between the BCA after HSSO and BSSO were at each displacement (p < 0.001), except for the achieved BCA after 8-mm setback and advancement (p ≥ 0.266). No significant differences were observed regarding ICD, except for the expected ICD after 8-mm setback and advancement (p ≤ 0.037). CONCLUSIONS: Compared to the virtual planning, the predictability regarding BCA and ICD was limited. ICD showed smaller clinical changes, BCA decreased significantly in the BSSO group. CLINICAL RELEVANCE: BCA and ICD might have been less important in choosing the suitable split technique. in orthognathic surgery.

A new flavonolignan from milk thistle (Silybum marianum).

A new flavonolignan, sonyamandin (1), along with other known compounds was isolated from the aerial parts and seeds extracts of Silybum marianum (milk thistle) collected from Jordan. The known ones are ursolic acid (2), oleanolic acid (3), maslinic acid (4), oleic acid (5), ß-sitosterol (6), ß-, sitosteryl glucoside (7), apigenin (8), kaempferol-3-O-rhamnoside (9), apigenin-7-O-ß-D-glycoside (10), isosylibin A (11), isosylibin B (12), and silybin B (13). The absolute stereochemistry of 1 was confirmed by 2D NMR and CD analysis.

Stigmasterol: An Enigmatic Plant Stress Sterol with Versatile Functions.

Sterols play important structural and regulatory roles in numerous intracellular processes. Unlike animals, plants contain a distinctive and diverse variety of sterols. Recently, information has emerged showing that stigmasterol is a "stress sterol". Stigmasterol is synthesized via the mevalonate biosynthesis pathway and has structural similarity to ß-sitosterol but differs in the presence of a trans-oriented double bond in the side chain. In plants, the accumulation of stigmasterol has been observed in response to various stresses. However, the precise ways that stigmasterol is involved in the stress responses of plants remain unclear. This comprehensive review provides an update on the biology of stigmasterol, particularly the physicochemical properties of this ethylsterol, its biosynthesis, and its occurrence in higher plants and extremophilic organisms, e.g., mosses and lichens. Special emphasis is given to the evolutionary aspects of stigmasterol biosynthesis, particularly the variations in the gene structure of C22-sterol desaturase, which catalyzes the formation of stigmasterol from ß-sitosterol, in a diversity of evolutionarily distant organisms. The roles of stigmasterol in the tolerance of plants to hostile environments and the prospects for its biomedical applications are also discussed. Taken together, the available data suggest that stigmasterol plays important roles in plant metabolism, although in some aspects, it remains an enigmatic compound.

Synthesis of novel nonsteroidal anti-inflammatory galloyl ß-sitosterol-loaded lignin-capped Ag-based drug.

Biocompatible anti-inflammatory lignin-capped Ag (LCAg) nanoparticles (NPs) were synthesized for the delivery of galloyl ß-sitosterol (Galloyl-BS). ß-Sitosterol (BS) is effective against inflammatory responses, like cancer-induced inflammations. BS was modified via gallic acid esterification to enhance its anti-inflammatory potential. LCAg NPs were synthesized by a green method and loaded with galloyl-BS. For comparison, pure BS was also loaded onto LCAg NPs in a separate assembly. The antioxidant potential of Galloyl-BS was greater (IC50 177 µM) than pure BS. Materials were characterized by FT-IR, SEM, XRD, and Zeta potential. Using UV-Vis spectroscopy, drug release experiments were performed by varying pH, time, concentration, and temperature. Maximum drug release was observed after 18 h at pH 6 and 40 °C. Galloyl-BS showed improved drug loading efficiency, release %age, and antioxidant activity compared to pure BS when loaded onto LCAg NPs. DLCAg exhibited excellent anti-inflammatory activity in rat models. These findings indicate that galloyl-BS (drug)-loaded LCAg (DLCAg) NPs have the potential as an anti-inflammatory agent without any prior release and scavenging in normal cells.

Effect of different gelators on the physicochemical properties and microstructure of coconut oleogels.

BACKGROUND: The inherent properties of coconut oil (CO), including its elevated saturated fatty acid content and low melting point, make it suitable for application in plastic fat processing. The present study explores the physicochemical characteristics, micromorphology and oxidative stability of oleogels produced from CO using various gelators [ethylcellulose (EC), ß-sitosterol/γ-oryzanol (PS) and glyceryl monostearate (MG)] to elucidate the formation mechanisms of coconut oleogels (EC-COO, PS-COO and MG-COO). RESULTS: Three oleogel systems exhibited a solid-like behavior, with the formation of crystalline forms dominated by ß and ß'. Among them, PS-COO exhibited enhanced capability with respect to immobilizing liquid oils, resulting in solidification with high oil-binding capacity, moderate hardness and good elasticity. By contrast, MG-COO demonstrated inferior stability compared to PS-COO and EC-COO. Furthermore, MG-COO and PS-COO demonstrated antioxidant properties against CO oxidation, whereas EC-COO exhibited the opposite effect. PS-COO and EC-COO exhibited superior thermodynamic behavior compared to MG-COO. CONCLUSION: Three oleogels based on CO were successfully prepared. The mechanical strength, storage modulus and thermodynamic stability of the CO oleogel exhibited concentration dependence with increasing gelling agent addition. PS-COO demonstrated relatively robust oil-binding capacity and oxidative stability, particularly with a 15% PS addition. This information contributes to a deeper understanding of CO-based oleogels and offers theoretical insights for their application in food products. © 2024 Society of Chemical Industry.

Mucoadhesive Chitosan Composite Sponge as a Carrier for ß-Sitosterol Cubosomes for Thermal Burn Treatment.

Our study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of ß-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 ß-sitosterol cubosomal sponge showed significant higher wound closure percentage relative to the ß-sitosterol product (Mebo)®.

Nutritional Value, Phytochemical Composition and Biological Activities of Lycium barbarum L. fruits from Serbia.

Cultivation of goji berries (GB), fruits of Lycium barbarum L. (Solanaceae), is expanding worldwide, including in Europe. In this study, a comparative analysis of the nutritional value, chemical composition and in vitro biological activities of GB from different locations in Serbia was performed. Proximate compositions were evaluated according to standard methods. Minerals were assessed by inductively coupled plasma techniques, while fatty acids, sterols, and phenolic profiles were analyzed by gas- and liquid chromatography-based techniques coupled with flame-ionization, mass spectrometry, or diode array detection. The total content of phenolics, flavonoids, carotenoids, and polysaccharides was assessed using spectrophotometric methods. Methanol extracts from GB were examined for their antioxidant, enzyme inhibitory (α-amylase, α-glucosidase, acetylcholinesterase and tyrosinase) and antibacterial activities. Despite significant variations among samples from different locations, the results confirmed that GB are a valuable source of dietary fiber and protein and are characterized by favorable fatty acid profiles. Phytochemical analysis revealed that ß-sitosterol, Δ5-avenasterol, and 24-methyldesmosterol are the predominant sterols and caffeic acid, gallic acid, quercetin and rutin are the main phenols. All GB samples showed both antioxidant and mild antimicrobial activity. A dose-dependent anti-enzymatic activity (IC50 ranging 1.68-6.88 mg/mL) was demonstrated. The results support further promotion of GB cultivation in Serbia and further investigations on their potential applications in various industries.