Quantitative Proteomic Analysis Reveals the Mechanisms of Sinapine Alleviate Macrophage Foaming.

Rapeseed polyphenols have cardiovascular protective effects. Sinapine, one main rapeseed polyphenol, possesses antioxidative, anti-inflammatory, and antitumor properties. However, no research has been published about the role of sinapine in alleviating macrophage foaming. This study aimed to reveal the macrophage foaming alleviation mechanism of sinapine by applying quantitative proteomics and bioinformatics analyses. A new approach was developed to retrieve sinapine from rapeseed meals by using hot-alcohol-reflux-assisted sonication combined with anti-solvent precipitation. The sinapine yield of the new approach was significantly higher than in traditional methods. Proteomics was performed to investigate the effects of sinapine on foam cells, and it showed that sinapine can alleviate foam cell formation. Moreover, sinapine suppressed CD36 expression, enhanced the CDC42 expression, and activated the JAK2 and the STAT3 in the foam cells. These findings suggest that the action of sinapine on foam cells inhibits cholesterol uptake, activates cholesterol efflux, and converts macrophages from pro-inflammatory M1 to anti-inflammatory M2. This study confirms the abundance of sinapine in rapeseed oil by-products and elucidates the biochemical mechanisms of sinapine that alleviates macrophage foaming, which may provide new perspectives for reprocessing rapeseed oil by-products.

Xuanfei Baidu Decoction reduces acute lung injury by regulating infiltration of neutrophils and macrophages via PD-1/IL17A pathway.

The pathogenic hyper-inflammatory response has been revealed as the major cause of the severity and death of the Corona Virus Disease 2019 (COVID-19). Xuanfei Baidu Decoction (XFBD) as one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, shows unique advantages in the control of symptomatic transition from moderate to severe disease states. However, the roles of XFBD to against hyper-inflammatory response and its mechanism remain unclear. Here, we established acute lung injury (ALI) model induced by lipopolysaccharide (LPS), presenting a hyperinflammatory process to explore the pharmacodynamic effect and molecular mechanism of XFBD on ALI. The in vitro experiments demonstrated that XFBD inhibited the secretion of IL-6 and TNF-α and iNOS activity in LPS-stimulated RAW264.7 macrophages. In vivo, we confirmed that XFBD improved pulmonary injury via down-regulating the expression of proinflammatory cytokines such as IL-6, TNF-α and IL1-ß as well as macrophages and neutrophils infiltration in LPS-induced ALI mice. Mechanically, we revealed that XFBD treated LPS-induced acute lung injury through PD-1/IL17A pathway which regulates the infiltration of neutrophils and macrophages. Additionally, one major compound from XFBD, i.e. glycyrrhizic acid, shows a high binding affinity with IL17A. In conclusion, we demonstrated the therapeutic effects of XFBD, which provides the immune foundations of XFBD and fatherly support its clinical applications.

Identification and Capture of Phenolic Compounds from a Rapeseed Meal Protein Isolate Production Process By-Product by Macroporous Resin and Valorization Their Antioxidant Properties.

In this study, phenolic compounds from an aqueous protein by-product from rapeseed meal (RSM) were identified by HPLC-DAD and HPLC-ESI-MS, including sinapine, sinapic acid, sinapoyl glucose, and 1,2-di-sinapoyl gentibiose. The main phenolic compound in this by-product was sinapine. We also performed acid hydrolysis to convert sinapine, and sinapic acid derivatives present in the permeate, to sinapic acid. The adsorption of phenolic compounds was investigated using five macroporous resins, including XAD4, XAD7, XAD16, XAD1180, and HP20. Among them, XAD16 showed the highest total phenolic contents adsorption capacities. The adsorption behavior of phenolic compounds was described by pseudo-second-order and Langmuir models. Moreover, thermodynamics tests demonstrated that the adsorption process of phenolic compounds was exothermic and spontaneous. The highest desorption ratio was obtained with 30% (v/v) and 70% (v/v) ethanol for sinapine and sinapic acid, respectively, with a desorption ratio of 63.19 ± 0.03% and 94.68 ± 0.013%. DPPH and ABTS tests revealed that the antioxidant activity of the hydrolyzed fraction was higher than the non-hydrolyzed fraction and higher than the one of vitamin C. Antioxidant tests demonstrated that these phenolic compounds could be used as natural antioxidants, which can be applied in the food industry.

Selective Extraction of Sinapic Acid Derivatives from Mustard Seed Meal by Acting on pH: Toward a High Antioxidant Activity Rich Extract.

The aim of this paper is to study the effect of the pH on the extraction of sinapic acid and its derivatives from mustard seed meal. Solutions of acidic pH (pH 2), basic pH (pH 12) and distilled water (uncontrolled pH ~ 4.5) were tested at different percentages of ethanol. The maximum extraction yield for sinapic acid (13.22 µmol/g of dry matter (DM)) was obtained with a buffered aqueous solution at pH 12. For ethyl sinapate, the maximum extraction yield reached 9.81 µmol/g DM with 70% ethanol/buffered aqueous solution at pH 12. The maximum extraction yield of sinapine (15.73 µmol/g DM) was achieved with 70% ethanol/buffered aqueous solution at pH 2. The antioxidant activity of each extract was assessed by DPPH assay; the results indicated that the extracts obtained at pH 12 and at low ethanol percentages (<50%) exhibit a higher antioxidant activity than extracts obtained at acidic conditions. Maximum antioxidant activity was reached at pH 12 with buffer solution (11.37 mg of Trolox Equivalent/g DM), which confirms that sinapic acid-rich fractions exhibit a higher antioxidant activity. Thus, to obtain rich antioxidant extracts, it is suggested to promote the presence of sinapic acid in the extracts.

[Extraction and Separation of Sinapine from Rapeseed Cake and the Mode of Action of Melanin Production Inhibition].

Brassica campestris L. is the important oil-bearing crop in China. Rapeseed cake is the main byproduct of rapeseed oil extraction. As the main active ingredient in rapeseed cake, sinapine has several important biological activities. Therefore, the inhibitory activity of sinapine on tyrosinase in vitro and its free radical-scavenging rate were determined. Tyrosinase activity in A-375 human melanocytes was also investigated and the effects of sinapine on the melanin content and its antioxidant effects on melanin biosynthesis were studied. The results showed that sinapine had significant antioxidant activity. Sinapine significantly inhibited A-375 human melanocytes in a dose-dependent manner. Sinapine inhibited melanin synthesis in A-375 cells by downregulating the mRNA and protein expression of TRP-1, TRP-2, and MITF factors. The results showed that rapeseed cake sinapine inhibited melanin production and could be used as a potential active ingredient in the development of whitening agents.

Anti-photoaging effects of canola meal extract on human dermal fibroblasts against UVB-induced oxidative stress.

Canola meal, a by-product of canola oil processing, is a source of bioactive compounds that show antioxidant and skin anti-aging effects through upcycling (i.e., creative reuse). Here we describe the antioxidant and skin anti-aging effects of canola meal extract (CME) obtained by upcycling canola meal. The antioxidant capacity of CME is due in part to its antioxidative phenolics. Seven phenolics, including sinapine and sinapic acid, in CME were identified using ultra-high-performance liquid chromatography-Orbitrap mass spectrometry. Addition of CME (1000 µg/mL) to human dermal fibroblast neonatal cells  significantly (p < 0.05) reduced matrix metalloproteinase-12 production and increased pro-collagen Ι alpha 1 content in response to ultraviolet B-induced oxidative stress compared with cells without CME. These results suggest that CME can serve as a functional food ingredient with antioxidant capacity and anti-aging effects on the skin.

Sinapine thiocyanate alleviates intervertebral disc degeneration by not regulating JAK1/STAT3/NLRP3 signal pathway.

BACKGROUND: Intervertebral disc degeneration (IDD) is a major cause of low back pain. Sinapine thiocyanate (ST) has been reported to have a wide range of biological activities. However, the treatment of IDD with ST has not been studied. OBJECTIVES: To explore the role and mechanism of ST treatment in IDD. MATERIAL AND METHODS: Nucleus pulposus cells (NPCs) were induced using lipopolysaccharide (LPS), which was used as an in vitro model of IDD. Cell activity, oxidative stress-related indicators and protein expression were detected using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, enzyme-linked immunosorbent assay (ELISA) and western blot. Pyroptosis was evaluated with propidium iodide (PI)/Hoechst double staining and immunofluorescence for NOD-like receptor protein 3 (NLRP3), and pyroptosis-related proteins and inflammatory factors were measured with western blot and ELISA. The pathological changes of IDD were assessed with hematoxylin & eosin (H&E) and safranin-O staining. RESULTS: Our results showed that ST alleviated LPS-induced degeneration of NPCs, as evidenced by reducing reactive oxygen species (ROS), malondialdehyde (MDA), matrix metalloproteinase-13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and increasing collagen II and aggrecan expression. Moreover, ST repressed LPS-induced pyroptosis by inhibiting NLRP3, caspase-1 p20, interleukin (IL)-1ß and IL-18. Further studies showed that ST did not restrain the activation of the JAK1/STAT3 signaling pathway induced by colivelin, or of the enhanced pyroptosis induced by polyphyllin VI. Sinapine thiocyanate alleviated IDD in vivo and suppressed NLRP3-mediated pyroptosis and the JAK1/STAT3 signaling pathway. CONCLUSIONS: Sinapine thiocyanate could alleviate IDD, although this did not include a reduction in NLRP3-mediated pyroptosis and inactivation of the JAK1/STAT3 signaling pathway, thus potentially being a candidate drug for IDD treatment.

Sinapine targeting PLCß3 EF hands disrupts Gαq-PLCß3 interaction and ameliorates cardiovascular diseases.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) over-activation is highly involved in cardiovascular diseases (CVDs), with the Gαq-PLCß3 axis acting as a core node of RAAS. PLCß3 is a potential target of CVDs, and the lack of inhibitors has limited its drug development. PURPOSE: Sinapine (SP) is a potential leading compound for treating CVDs. Thus, we aimed to elucidate the regulation of SP towards the Gαq-PLCß3 axis and its molecular mechanism. STUDY DESIGN: Aldosteronism and hypertension animal models were employed to investigate SP's inhibitory effect on the abnormal activation of the RAAS through the Gαq-PLCß3 axis. We used chemical biology methods to identify potential targets and elucidate the underlying molecular mechanisms. METHODS: The effects of SP on aldosteronism and hypertension were evaluated using an established animal model in our laboratory. Target identification and underlying molecular mechanism research were performed using activity-based protein profiling with a bio-orthogonal click chemistry reaction and other biochemical methods. RESULTS: SP alleviated aldosteronism and hypertension in animal models by targeting PLCß3. The underlying mechanism for blocking the Gαq-PLCß3 interaction involves targeting the EF hands through the Asn-260 amino acid residue. SP regulated the Gαq-PLCß3 axis more precisely than the Gαq-GEFT or Gαq-PKCζ axis in the cardiovascular system. CONCLUSION: SP alleviated RAAS over-activation via Gαq-PLCß3 interaction blockade by targeting the PLCß3 EF hands domain, which provided a novel PLC inhibitor for treating CVDs. Unlike selective Gαq inhibitors, SP reduced the risk of side effects compared to Gαq inhibitors in treating CVDs.

Sinapine thiocyanate exhibited anti-colorectal cancer effects by inhibiting KRT6A/S100A2 axis.

Sinapine thiocyanate (ST), an alkaloid existed extensively in seeds of cruciferous plants, exhibits a number of pharmacological effects, including anti-inflammatory and anti-malignancy properties. However, it is still unknown what effects and molecular mechanisms ST has on colorectal cancer (CRC). In the current study, it was indicated that ST inhibited proliferation, colony formation, and apoptosis in vitro, as well as arrested the G1 phase of CRC cells. There was a significant repressive effects of ST on invasion and migration of CRC cells in vitro. RNA-sequencing indicated that 750 differentially expressed genes existed in CRC cells after ST treatment, and enrichment analysis demonstrated that ST obviously decreased the activation of keratinization pathways. Among DEGs enriched in keratinization, keratin 6A (KRT6A) was decreased the most significant, as well as its target gene S100 calcium-binding protein A2 (S100A2). Low expression of KRT6A and S100A2 signatures indicated a favorable prognosis in CRC patients. Moreover, we found overexpression of KRT6A relieved the inhibitory effects of ST in CRC cells. Furthermore, ST inhibited the CRC cell proliferation in vivo, and reduced KRT6A and KI67 expression in xenograft tumor. Taken together, we demonstrated that ST exhibited anti-CRC properties by inhibiting KRT6A/S100A2 axis. It is possible that ST can be used as a treatment for CRC.

Optimization of Canolol Production from Canola Meal Using Microwave Digestion as a Pre-Treatment Method.

Canola meal, the by-product of canola oil refining, is a rich source of phenolic compounds and protein. The meal, however, is primarily utilized as animal feed but represents an invaluable source of nutraceuticals. Of particular interest are the sinapates, sinapine and sinapic acid, with the decarboxylation of the latter to form canolol. Extracting these phenolics has been carried out using a variety of different methods, although there is an urgent need for environmentally safe and sustainable methods. Microwave-assisted solvent extraction (MAE), as a green extraction method, is receiving considerable interest. Its ease of use makes MAE one of the best methods for studying multiple solvents. The formation of canolol, from sinapine and sinapic acid, is primarily dependent on temperature, which favors the decarboxylation reaction. The application of MAE, using the MultiwaveTM 500 microwave system with green extractants, was undertaken to assess its ability to enhance the yield of sinapates and canolol. This study examined the effects of different pre-treatment temperature-time combinations of 140, 150, 160, and 170 °C for 5, 10, 15, 20, and 30 min on the extraction of canolol and other canola endogenous phenolic compounds. Total phenolic content (TPC), total flavonoid content (TFC), as well as metal ion chelation (MIC) and DPPH radical activity of the different extracts were assessed. The results confirmed that extractability of canolol was optimized with methanol at 151 °C and with ethanol at 170 °C with pre-treatment times of 15.43 min and 19.31 min, respectively. Furthermore, there was a strong positive correlation between TPC and TFC (p < 0.05) and a negative correlation between TFC and DPPH radical activity. Interestingly, no significant correlation was observed between MIC and DPPH. These results confirmed the effectiveness of MAE, using the novel MultiwaveTM 500 microwave instrument, to enhance the yield of canolol. This was accompanied by substantial improvements in the antioxidant activity of the different extracts and further established the efficacy of the current MAE method for isolating important natural phenolic derivatives for utilization by the nutraceutical industry.

Improvement of Sinapine Extraction from Mustard Seed Meal by Application of Emerging Technologies.

Sinapine is a phenolic compound found in mustard (Brassica juncea) seed meal. It has numerous beneficial properties such as antitumor, neuroprotective, antioxidant, and hepatoprotective effects, making its extraction relevant. In this study, the extraction of sinapine was investigated using three methods: (i) from a mustard seed meal defatted by a supercritical CO2 (SC-CO2) pretreatment, (ii) by the implementation of high-voltage electrical discharges (HVEDs), (iii) and by the use of ultrasound. The use of SC-CO2 pretreatment resulted in a dual effect on the valorization of mustard seed meal, acting as a green solvent for oil recovery and increasing the yield of extracted sinapine by 24.4% compared to the control. The combination of ultrasound and SC-CO2 pretreatment further increased the yield of sinapine by 32%. The optimal conditions for ultrasound-assisted extraction, determined through a response surface methodology, are a temperature of 75 °C, 70% ethanol, and 100% ultrasound amplitude, resulting in a sinapine yield of 6.90 ± 0.03 mg/g dry matter. In contrast, the application of HVEDs in the extraction process was not optimized, as it led to the degradation of sinapine even at low-energy inputs.

Metabolic profiling and pharmacokinetic studies of sinapine thiocyanate by UHPLC-Q/TOF-MS and UHPLC-MS/MS.

Sinapine thiocyanate (ST) is an index component and pharmacological active component of Semen Sinapis and Semen Raphani, and it is widely used to relieving cough and asthma. This study aimed to obtain the metabolic and pharmacokinetic characterization of ST. The metabolic profiles of ST were obtained from rat plasma, urine, and feces via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q/TOF-MS). Thirteen metabolites were structurally identified, and the proposed metabolic pathways of ST included deamination, demethylation, hydrogenation, dehydration, and extensive conjugation, including glucuronidation and sulfonation. ST was selected as the plasma marker for the pharmacokinetic study. A simple and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the quantitation of ST in rat plasma. The linear range of ST was 0.1-500 ng/mL (R2 = 0.9976), and the lowest limit of quantification was 0.1 ng/mL. The intra-precision and inter-precision of the assay were 1.31-5.12% and 2.72-7.66%, and the accuracy (RE%) ranged from - 4.88% to 3.82% and - 3.47% to 6.18%. The extraction recovery, matrix effect, and stability of ST were within acceptable limits. The established method was validated and successfully applied to the pharmacokinetic study of ST. For pharmacokinetic experiments, the male Sprague-Dawley rats were administrated with ST solution intravenously (2 mg/kg) or orally (100 mg/kg). The oral absolute bioavailability of ST was calculated as 1.84%, and the apparent volume of distribution of intravenous and intragastric administrations were 107.51 ± 21.16 L/kg and 78.60 ± 14.44 L/kg, respectively. The maximum plasma concentration was 47.82 ± 18.77 nM, and the time to maximum peak was 88.74 ± 20.08 min for the intragastric dosing group. According to the pharmacokinetic and metabolic profiling results, metabolites with high abundance of ST in bio-fluids would be the next object in tissue distribution and pharmacodynamic study.

Sinapine induced ferroptosis in non-small cell lung cancer cells by upregulating transferrin/transferrin receptor and downregulating SLC7A11.

Sinapine (SI) is a naturally occurring product with biological properties, but its activity against non-small cell lung cancer (NSCLC) remains unclear. This research examined the anti-tumour effects of SI in NSCLC cells and the underlying mechanisms of any effects. SI induced ferroptosis, a novel form of cell death, by increasing intracellular ferrous iron, lipid peroxidation, and reactive oxygen species (ROS) in NSCLC cells. SI treatment resulted in transferrin and transferrin receptor upregulation, and inhibition of transferrin or the transferrin receptor reduced the ferroptosis caused by SI. SI treatment also resulted in a p-53 dependent downregulation of SLC7A11. Finally, we evaluated the effects of SI in vivo and it was found that SI also successfully inhibited the growth of NSCLC in vivo. In summary, our data demonstrated that SI triggered ferroptosis in NSCLC cells and may be a promising therapeutic agent for this condition.

Sinapine improves LPS-induced oxidative stress in hepatocytes by down-regulating MCJ protein expression.

Oxidative stress is an important part of the development of NAFLD, and hepatic injury can be prevented by inhibiting oxidative stress. In this study, we investigated the potential role of sinapine in protecting the liver. LPS was selected to establish the oxidative stress model of THLE-2 cells, and the treatment concentrations of LPS (5 µg/mL) and sinapine (5 µM, 20 µM, and 80 µM) were determined by toxicity experiments. The MDA of the sinapine (80 µM) pretreatment group was 1.09 ± 0.13 nmol/mg prot which was reduced by 27.67 % compared with the LPS group. Furthermore, SOD and GSH-Px levels were significantly increased by 40.61 % and 49.60 %, respectively. And the ROS levels of 20 and 80 µM sinapine were reduced by 31.47 % and 40.31 %, respectively (p < 0.01) compared with the model group. The mitochondrial membrane potential had similar results. It was also found that sinapine can significantly down-regulate the level of MCJ protein (p < 0.01), which is related to oxidative stress. Our results indicate that sinapine can maintain liver health by down-regulating the expression of MCJ protein to inhibit oxidative stress, which provides a theoretical basis for the use of sinapine as an inhibitor of MCJ.

Transdermal delivery of sinapine thiocyanate by gelatin microspheres and hyaluronic acid microneedles for allergic asthma in guinea pigs.

Dissolving microneedles (MNs) are an efficient, safe, and generally painless method for transdermal distribution of poorly permeable medicines. Here, dissolving composite MNs were prepared from sinapine thiocyanate (ST)-loaded gelatin microspheres (GMS) and hyaluronic acid (HA). To immobilize ST in MNs, we used a two-step centrifuging and molding method. When ST-GMS/ST-HA MNs were placed on the skin, they showed extraordinary mechanical strength and dissolved slowly. In vitro, skin implantation ability was assessed with fluorescein isothiocyanate staining, which revealed progressive penetration from the puncture site into deeper tissues. The feasibility of transdermal delivery of ST-GMS/ST-HA MNs in allergic asthma guinea pigs was then determined through in vivo pharmacodynamic and pharmacokinetic tests. The results indicated that ST-GMS/ST-HA MNs, in comparison with the traditional subcutaneous application approach, achieved both high efficiency and continuous release of ST. Therefore, this device is promising for the delivery ST for allergic asthma therapy.

Sinapine Thiocyanate Inhibits the Proliferation and Mobility of Pancreatic Cancer Cells by Up-Regulating GADD45A.

Background: Sinapine thiocyanate (ST), an alkaloid isolated from the seeds of cruciferous species, has exhibited anti-inflammatory, anti-malignancy, and anti-angiogenic effects in previous studies. However, the effects and molecular mechanisms of action of ST in pancreatic cancer (PC) are still limited. Materials and methods: PC cells were treated with different concentrations (0, 20, 40, and 80 µM) of ST. The proliferative ability of PC cells in vitro was determined using cell count kit-8 (CCK-8), 5-ethynyl-2' deoxyuridine, colony formation, and flow cytometry assays. The mobility of PC cells in vitro was analyzed using wound healing assay, transwell assay, Western blotting, and immunofluorescence. High-throughput sequencing followed by bioinformatics analysis, reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), and Western blotting were performed to identify the key targets of ST. Finally, CCK-8 assay, wound healing assay, and xenograft tumor model were used to determine the relationship between ST and growth arrest and DNA damage-inducible alpha (GADD45A; the key target of ST) and malignant biological properties of PC in vitro and in vivo. Results: ST significantly repressed the PC cell proliferation rate and colony formation in vitro and arrested cells in the G2/M phase. ST inhibited PC cell mobility in vitro and increased E-cadherin expression (an epithelial biomarker). GADD45A was considered the key target of ST in PC and was elevated in PC cells treated with ST. The inhibition of GADD45A significantly alleviated the suppressive effects of ST on PC cell proliferation and mobility in vitro. ST suppressed PC cell proliferation in vivo and increased GADD45A expression in tumor tissues. Conclusion: ST exhibited significant anti-tumor effects on PC cells by upregulating GADD45A. ST may be a potential drug for PC treatment.

Covalent immobilization of beta2 adrenergic receptor through trans-methylation reaction by SNAP-tag and its application in anti-asthmatic compound screening from Raphani Semen.

Beta2-adrenergic receptor (ß2-AR) is believed as an attractive target for anti-asthmatic drugs. Its crystal structure and pharmacological activity have been clearly investigated. Yet the number of the approved anti-asthmatic drugs has declined in recent years. This work reports on the preparation of an immobilized ß2-AR column through the specific trans-methylation reaction between SNAP tag and the benzyl-guanine derivative and application in anti-asthmatic compound screening from Raphani Semen. The characterization of the immobilized ß2-AR was performed by scanning electron microscopy (SEM) and receptor-ligand interaction analysis by chromatographic methods. SEM analysis showed that the receptor has been successfully coated on the surface of PEGA amino microspheres. Binding constants of salbutamol and terbutaline calculated from frontal analysis within the temperature range of 10-30 â„ƒ confirmed the feasibility of the method in a thermodynamic viewpoint. Hydrogen bond was verified as the main driving force for drug-receptor interaction analysis. Sinapine was identified as the potential bioactive compound in Raphani Semen that specifically bind with ß2-AR with a specific binding site of Ser 207. Taking together, the immobilized ß2-AR column is promising in exploring drug-protein interaction analysis and anti-asthmatic drug screening.

Sinapic Acid and Sinapate Esters in Brassica: Innate Accumulation, Biosynthesis, Accessibility via Chemical Synthesis or Recovery From Biomass, and Biological Activities.

Sinapic acid (SinA) and corresponding esters are secondary metabolites abundantly found in plants of Brassica family. Belonging to the family of p-hydroxycinnamic acids, SinA and its esters analogues are present in different plant parts and involved in multiple biological processes in planta. Moreover, these metabolites are also found in relatively large quantities in agro-industrial wastes. Nowadays, these metabolites are increasingly drawing attention due to their bioactivities which include antioxidant, anti-microbial, anti-cancer and UV filtering activities. As a result, these metabolites find applications in pharmaceutical, cosmetic and food industries. In this context, this article reviews innate occurrence, biosynthesis, accessibility via chemical synthesis or direct extraction from agro-industrial wastes. Biological activities of SinA and its main corresponding esters will also be discussed.

Serum trimethylamine-N-oxide and gut microbiome alterations are associated with cholesterol deposition in the liver of laying hens fed with rapeseed meal.

Sinapine derived from cruciferous plants could be converted into trimethylamine by intestinal microbiota. Its metabolite, trimethylamine N-oxide (TMAO), is closely linked to increased risk of cardiovascular disease and fat deposition in mammals. Hens fed with rapeseed meal (RSM) suffered from fatty liver hemorrhage syndrome (FLHS). This study was conducted to investigate whether RSM-induced fatty liver is due to TMAO via altering microbiota composition and diversity. At 33 weeks of age, 600 laying hens were randomly divided into 5 treatment groups, namely control and 14% RSM treatment groups (DY5, with 16.2% erucic acid [EA] and 74.66% glucosinolate [Gl] contents; MB1, with 3.50% EA and 43.23% Gl contents; DY6, with 6.7% EA and 22.67% Gl contents; XH3, with 44.60% EA and 132.83% Gl contents) for 8 weeks. Results revealed that 3 hens died due to liver hemorrhage after ingesting 14% RSM diet. The 14% RSM decreased serum low-density lipoprotein cholesterol (LDL-C) content (P < 0.01) while tended to increase serum TMAO content compared to the control group (P = 0.08). The 14% RSM diet increased red oil O optical density (P < 0.01), and increased total cholesterol (TC) and LDL-C content in the liver (P < 0.01, and P < 0.01, respectively). The 14% RSM decreased liver total bile acid (TBA) content compared to the control (P < 0.01). The DY6 had a higher TBA content in the liver than the XH3 (P < 0.01). The 14% RSM decreased mRNA abundance of liver X receptors alpha (LXR-α, P = 0.01), and increased mRNA abundance of sterol response element binding protein 2 (SREBP-2, P = 0.04). Results revealed that the in-feed RSM could alter richness and diversity of cecal microbiota compared to the control (P < 0.05). Liver TC content and serum TMAO showed a negative relationship with Proteobacteria and Actinobacteria (P = 0.04). In conclusion, 14% RSM increased liver TC and induced high liver score of FLHS, which was possibly associated with the altered cecal microbiota composition, increased serum TMAO levels and LXR-α and SREBP-2 expressions.

Sinapine Thiocyanate Ameliorates Vascular Endothelial Dysfunction in Hypertension by Inhibiting Activation of the NLRP3 Inflammasome.

The increase of blood pressure is accompanied by the changes in the morphology and function of vascular endothelial cells. Vascular endothelial injury and hypertension actually interact as both cause and effect. A large number of studies have proved that inflammation plays a significant role in the occurrence and development of hypertension, but the potential mechanism between inflammation and hypertensive endothelial injury is still ambiguous. The purpose of this study was to explore the association between the activation of NLRP3 inflammasome and hypertensive endothelial damage, and to demonstrate the protective effect of sinapine thiocyanate (ST) on endothelia in hypertension. The expression of NLRP3 gene was silenced by tail vein injection of adeno-associated virus (AAVs) in spontaneously hypertensive rats (SHRs), indicating that activation of NLRP3 inflammasome accelerated hypertensive endothelial injury. ST not only protected vascular endothelial function in SHRs by inhibiting the activation of NLRP3 inflammasome and the expression of related inflammatory mediators, but also improved AngII-induced huvec injury. In summary, our results show that alleviative NLRP3 inflammasome activation attenuates hypertensive endothelial damage and ST ameliorates vascular endothelial dysfunction in hypertension via inhibiting activation of the NLRP3 inflammasome.