Fatty Amide Research Articles

Efficacy and safety of JNJ-42165279, a fatty acid amide hydrolase inhibitor, in adolescents and adults with autism spectrum disorder: a randomized, phase 2, placebo-controlled study.

JNJ-42165279, a highly selective and orally bioavailable fatty acid amide (FAA) hydrolase inhibitor, was evaluated for efficacy and safety in adolescents and adults with autism spectrum disorder (ASD) in this phase 2, double-blind, placebo-controlled, multicenter study (NCT03664232). Participants aged 13-35 years, with a diagnosis of ASD (Diagnostic and Statistical Manual of Mental Disorders, 5th edition; Autism Diagnostic Observation Schedule, 2nd edition) were randomized (1:1) to 12 weeks of treatment with JNJ-42165279 (25 mg, twice-daily) or placebo. Primary endpoints were the change in the Autism Behavior Inventory (ABI) Core Domain (ABI-CD), ABI-Social Communication (ABI-SC), and ABI-Repetitive/Restrictive Behavior (ABI-RB) scores from baseline to day 85. Of the 61 participants (16 female, 45 male) included in the efficacy analyses, 53 (87%) completed the double-blind treatment. At day 85, the JNJ-42165279 group did not show a statistically significant reduction in ASD symptoms versus placebo, as assessed with ABI-CD (p = 0.284), ABI-SC (p = 0.290), and ABI-RB (p = 0.231). However, the following secondary outcomes exhibited small to moderate changes directionally favoring JNJ-42165279: Social Responsiveness Scale 2 (SRS, p = 0.064), Repetitive Behavior Scale-Revised (RBS-R, p = 0.006), Zarit Burden Interview short version (ZBI, p = 0.063), Child Adolescent Symptom Inventory-Anxiety (CASI-Anx, p = 0.048), and Caregiver Global Impression of Severity (p = 0.075). Notably, versus placebo, JNJ-42165279-treated participants showed increased concentrations of FAAs throughout the treatment period, with those achieving elevated concentrations experiencing the greatest reduction in the SRS total score at day 85. JNJ-42165279 demonstrated an acceptable safety profile. Although primary endpoints were not met, JNJ-42165279 may have a therapeutic effect on certain aspects of core ASD symptoms.

Copper(II)-catalyzed dehydration of primary amides to nitriles with the aid of trichloroacetonitrile

A method for the preparation of nitriles from primary amides using trichloroacetonitrile and a catalytic amount of cupric acetate is described. Using this method, amides including aromatic amides, aromatic heterocyclic amides and aliphatic amides were converted into the corresponding nitriles in moderate to good yields. Trichloroacetonitrile reacted with amide in the presence of cupric acetate to form trichloroacetamide, which has been isolated and confirmed.

Improved thermal, mechanical, and dielectric properties of thermotropic liquid crystalline poly(ester amide)s containing lactam-derived segmental units

We prepared two different series of thermotropic liquid crystalline poly(ester amide)s (TPEAs) via bulk polycondensation reactions of 4-hydroxybenzoic acid (HBA, 75.0 mol %) and 6-hydroxy-2-naphthoic acid (HNA, 25.0–17.5 mol %) with ε-caprolactam (CL, 0.0–7.5 mol %) or γ-butyrolactam (BL, 0.0–7.5 mol %). Our investigation aimed to explore the impact of lactam-derived aliphatic amide units’ length and content on the liquid crystalline feature, microstructure, thermal transition, thermal stability, mechanical/relaxational/rheological behavior, and dielectric characteristics of TPEAs. The molecular structure and fibrillar formation of TPEAs containing aliphatic amide units were confirmed through FT-IR and SEM analysis. With increasing CL or BL-derived units from 1.0 mol % to 5.0 mol %, we observed an increase in crystallinity, glass transition temperature, melting temperature, complex melt viscosity, and storage modulus of TPEAs, attributed to the enhanced intermolecular hydrogen bonding interactions. However, at 7.5 mol % CL or BL-derived unit content, these properties decreased due to increased chain irregularity as well as lowered crystallinity. Notably, the dielectric constants (3.31–3.04 at 2 MHz) of TPEAs decreased with the increase of lactam-derived aliphatic amide units owing to the restricted chain mobility by intermolecular hydrogen bonding interactions. We believe that the TPEAs synthesized in this study hold significant potential for applications in technical plastics, superfibers, and printed circuit board materials.

Protein biomarker signatures of preeclampsia - a longitudinal 5000-multiplex proteomics study

We aimed to explore novel biomarker candidates and biomarker signatures of late-onset preeclampsia (LOPE) by profiling samples collected in a longitudinal discovery cohort with a high-throughput proteomics platform. Using the Somalogic 5000-plex platform, we analyzed proteins in plasma samples collected at three visits (gestational weeks (GW) 12–19, 20–26 and 28–34 in 35 women with LOPE (birth ≥ 34 GW) and 70 healthy pregnant women). To identify biomarker signatures, we combined Elastic Net with Stability Selection for stable variable selection and validated their predictive performance in a validation cohort. The biomarker signature with the highest predictive performance (AUC 0.88 (95% CI 0.85–0.97)) was identified in the last trimester of pregnancy (GW 28–34) and included the Fatty acid amid hydrolase 2 (FAAH2), HtrA serine peptidase 1 (HTRA1) and Interleukin-17 receptor C (IL17RC) together with sFLT1 and maternal age, BMI and nulliparity. Our biomarker signature showed increased or similar predictive performance to the sFLT1/PGF-ratio within our data set, and we were able to validate the biomarker signature in a validation cohort (AUC ≥ 0.90). Further validation of these candidates should be performed using another protein quantification platform in an independent cohort where the negative and positive predictive values can be validly calculated.

Modulation of chemotherapy-induced peripheral neuropathy by JZL195 through glia and the endocannabinoid system

Chemotherapy-induced peripheral neuropathy (CIPN) used to treat cancer, is a significant side effect with a complex pathophysiology, and its mechanisms remain unclear. Recent research highlights neuroinflammation, which is modulated by the endocannabinoid system (ECS) and associated with glial activation, and the role of toll-like receptor 4 (TLR4) in CIPN. This study aimed to investigate the effects of JZL195, an inhibitor of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and explore the connection between cannabinoid receptors and TLR4 in glial cells. A CIPN animal model was developed using cisplatin-injected male C57BL/6 mice. Mechanical and cold allodynia were assessed through von Frey and acetone tests. Western blot analysis was used to examine the expression of catabolic enzymes, cannabinoid receptors, glial cells, and neuroinflammatory factors in the dorsal root ganglia (DRGs) and spinal cord. Immunohistochemistry was used to investigate the colocalization of cannabinoid receptors and TLR4 in glial cells. JZL195 alleviated pain by inhibiting FAAH/MAGL, modulating the ECS and neuroinflammatory factors, and suppressing glial cell activity. Additionally, cannabinoid receptors and TLR4 colocalized with astrocytes and microglia in the spinal cord. This study highlights the therapeutic potential of JZL195 in modulating the ECS and suggests a correlation between cannabinoid receptors and TLR4 in spinal glial cells, providing insight into alleviating pain and neuroinflammation in CIPN.

Metabolic Profiling, Antioxidant, and Anti-lipase Activity from Combined Leaves Extracts of Tamarindus indica and Murraya paniculata: A Simplex Lattice Design Approach

Tamarindus indica leaves are recognized for their potent antioxidant and hypolipidemic properties, whereas Murraya paniculata leaves are known for their abilities to lower lipids and glucose levels. This study aimed to assess the combined extract of both leaves against pancreatic lipase inhibition and analyze their metabolomic profiles as an initial step toward developing a polyherbal treatment for hypertriglyceridemia. The extracts were subjected to Liquid Chromatography-High Resolution Mass Spectrometer (LC-HRMS) untargeted system coupled with Compounds Discoverer software to reveal their metabolomic profile. Subsequently, both individual extracts and their combination were evaluated for anti-lipase activity using pancreatic lipase enzyme with p-nitrophenyl butyrate as the substrate. The combination of the two extracts (0-300 μg/mL, 300 μg/mL in total) was prepared following the Simplex Lattice Experimental Design with 5 different composition variations. Results: The findings indicated that Tamarindus indica leaf extract (TIE) predominantly exhibited lipase inhibitory activity. Interestingly, the addition of Murraya paniculata extract (MPE) diminished this enzyme inhibitory effect. TIE was found to be rich in polyhydroxy flavonoids followed by fatty amides, whereas MPE contained mainly polymethoxy flavonoids, fatty amides, and coumarins. The presence of fatty amides in both extracts was identified as a potential cause for this incompatibility. In summary, Tamarindus indica leaf extract demonstrated strong lipase inhibition; however, its effectiveness was reduced when combined with Murraya paniculata extract, possibly due to primary fatty amides. Further research is necessary to explore strategies for eliminating these compounds and confirming their impact in vivo.

FAAH inhibitor URB597 shows anti-hyperalgesic action and increases brain and intestinal tissues fatty acid amides in a model of CRF1 agonist mediated visceral hypersensitivity in male rats.

The endocannabinoid (eCB) system includes ligands (anandamide and 2-arachidonoyl glycerol, 2-AG), receptors and catabolizing enzymes (fatty acid amide hydrolase, FAAH and monoacylglycerol lipase) expressed in both the brain and gut. We investigated whether the FAAH inhibitor, URB597, influenced visceral pain to colorectal distension (CRD) in an acute stress-related model of visceral hypersensitivity induced by the selective corticotropin-releasing factor receptor subtype 1 (CRF1) agonist, cortagine. Male Sprague-Dawley rats were injected subcutaneously (SC) with URB597 (3 mg/kg) or vehicle and 2 h later, intraperitoneally with cortagine (10 μg/kg) or vehicle. The visceromotor responses (VMR) were assessed to a first CRD (baseline) before injections, and to a second CRD 15 min after the last treatment. Brain, jejunum, and proximal colon were collected from treated and naïve rats for levels quantification of three fatty acid amides (FAAs) [anandamide (arachidonyl-ethanolamide, AEA), oleoyl-ethanolamide (OEA) and palmitoyl-ethanolamide (PEA)], and 2-AG. In separate animals, defecation/diarrhea were monitored after URB597 and cortagine. URB597 inhibited cortagine-induced increased VMR at 40 mmHg (89.0 ± 14.8% vs. 132.5 ± 15.6% for vehicle SC, p < 0.05) and 60 mmHg (107.5 ± 16.1% vs. 176.9 ± 24.4% for vehicle SC, p < 0.001) while not influencing basal VMR. In URB597 plus cortagine group, FAAs levels increased in the brain and intestinal tissue while 2-AG did not change. URB597 did not modify cortagine-induced defecation/diarrhea versus vehicle. URB597 shows efficacy to elevate brain and intestinal FAAs and to counteract the colonic hypersensitivity induced by peripheral activation of CRF1 signaling supporting a potential strategy of FAAH inhibitors to alleviate stress-related visceral hypersensitivity.

Receptor and metabolic insights on the ability of caffeine to prevent alcohol-induced stimulation of mesolimbic dopamine transmission

The consumption of alcohol and caffeine affects the lives of billions of individuals worldwide. Although recent evidence indicates that caffeine impairs the reinforcing properties of alcohol, a characterization of its effects on alcohol-stimulated mesolimbic dopamine (DA) function was lacking. Acting as the pro-drug of salsolinol, alcohol excites DA neurons in the posterior ventral tegmental area (pVTA) and increases DA release in the nucleus accumbens shell (AcbSh). Here we show that caffeine, via antagonistic activity on A2A adenosine receptors (A2AR), prevents alcohol-dependent activation of mesolimbic DA function as assessed, in-vivo, by brain microdialysis of AcbSh DA and, in-vitro, by electrophysiological recordings of pVTA DA neuronal firing. Accordingly, while the A1R antagonist DPCPX fails to prevent the effects of alcohol on DA function, both caffeine and the A2AR antagonist SCH 58261 prevent alcohol-dependent pVTA generation of salsolinol and increase in AcbSh DA in-vivo, as well as alcohol-dependent excitation of pVTA DA neurons in-vitro. However, caffeine also prevents direct salsolinol- and morphine-stimulated DA function, suggesting that it can exert these inhibitory effects also independently from affecting alcohol-induced salsolinol formation or bioavailability. Finally, untargeted metabolomics of the pVTA showcases that caffeine antagonizes alcohol-mediated effects on molecules (e.g. phosphatidylcholines, fatty amides, carnitines) involved in lipid signaling and energy metabolism, which could represent an additional salsolinol-independent mechanism of caffeine in impairing alcohol-mediated stimulation of mesolimbic DA transmission. In conclusion, the outcomes of this study strengthen the potential of caffeine, as well as of A2AR antagonists, for future development of preventive/therapeutic strategies for alcohol use disorder.

Proteomic profiling of oleamide-mediated polarization in a primary human monocyte-derived tumor-associated macrophages (TAMs) model: a functional analysis.

Tumor-associated macrophages (TAMs) play a critical function in the development of tumors and are associated with protumor M2 phenotypes. Shifting TAMs towards antitumor M1 phenotypes holds promise for tumor immunotherapy. Oleamide, a primary fatty acid amide, has emerged as a potent anticancer and immunomodulatory compound. However, the regulatory effects of oleamide on TAM phenotypes remain unclear. We used real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) techniques to study the influence of oleamide on primary human monocyte-derived TAM phenotypes, and we investigated the protein expression profiles based on mass spectrometry to analyze the effect of oleamide on macrophage polarization. Moreover, the advantageous binding scores between oleamide and these target candidate proteins are examined using molecular docking. Our study revealed that oleamide effectively suppressed the M2-like TAM phenotype by reducing interleukin (IL)-10 production and downregulating M2-like markers, including vascular endothelial growth factor A (VEGFA), MYC proto-oncogene, bHLH transcription factor (c-Myc), and mannose receptor C-type 1 (CD206). Moreover, the conditioned medium derived from oleamide-treated TAMs induces apoptosis of MDA-MB-231 breast cancer cells. Proteomic analysis identified 20 candidate up- and down-regulation proteins targeted by oleamide, showing modulation activity associated with the promotion of the M1-like phenotype. Furthermore, molecular docking demonstrated favorable binding scores between oleamide and these candidate proteins. Collectively, our findings suggest that oleamide exerts a potent antitumor effect by promoting the antitumor M1-like TAM phenotype. These novel insights provide valuable resources for further investigations into oleamide and macrophage polarization which inhibit the progression of breast cancer, which may provide insight into immunotherapeutic approaches for cancer.

The dominant white color trait of the melon fruit rind is associated with epicuticular wax accumulation.

Microscopic analyses and chemical profiling demonstrate that the white rind phenotype in melon fruit is associated with the accumulation of n-alkanes, fatty alcohols, aldehydes and wax esters. Serving as an indicator of quality, the rind (or external) color of fruit directly affects consumer choice. A fruit's color is influenced by factors such as the levels of pigments and deposited epicuticular waxes. The latter produces a white-grayish coating often referred to as "wax bloom". Previous reports have suggested that some melon (Cucumis melo L.) accessions may produce wax blooms, where a dominant white rind color trait was genetically mapped to a major locus on chromosome 7 and suggested to be inherited as a single gene named Wi. We here provide the first direct evidence of the contribution of epicuticular waxes to the dominant white rind trait in melon fruit. Our light and electron microscopy and gas chromatography-mass spectrometry (GC-MS) comparative analysis of melon accessions with white or green rinds reveals that the rind of melon fruit is rich in epicuticular waxes. These waxes are composed of various biochemical classes, including fatty acids, fatty alcohols, aldehydes, fatty amides, n-alkanes, tocopherols, triterpenoids, and wax esters. We show that the dominant white rind phenotype in melon fruit is associated with increased accumulation of n-alkanes, fatty alcohols, aldehydes and wax esters, which are linked with the deposition of crystal-like wax platelets on their surfaces. Together, this study broadens the understanding of natural variation in an important quality trait of melon fruit and promotes the future identification of the causative gene for the dominant white rind trait.

Cannabinol modulates the endocannabinoid system and shows TRPV1-mediated anti-inflammatory properties in human keratinocytes.

Cannabinol (CBN) is a secondary metabolite of cannabis whose beneficial activity on inflammatory diseases of human skin has attracted increasing attention. Here, we sought to investigate the possible modulation by CBN of the major elements of the endocannabinoid system (ECS), in both normal and lipopolysaccharide-inflamed human keratinocytes (HaCaT cells). CBN was found to increase the expression of cannabinoid receptor 1 (CB1) at gene level and that of vanilloid receptor 1 (TRPV1) at protein level, as well as their functional activity. In addition, CBN modulated the metabolism of anandamide (AEA) and 2-arachidonoylglicerol (2-AG), by increasing the activities of N-acyl phosphatidylethanolamines-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH)-the biosynthetic and degradative enzyme of AEA-and that of monoacylglycerol lipase (MAGL), the hydrolytic enzyme of 2-AG. CBN also affected keratinocyte inflammation by reducing the release of pro-inflammatory interleukin (IL)-8, IL-12, and IL-31 and increasing the release of anti-inflammatory IL-10. Of note, the release of IL-31 was mediated by TRPV1. Finally, the mitogen-activated protein kinases (MAPK) signaling pathway was investigated in inflamed keratinocytes, demonstrating a specific modulation of glycogen synthase kinase 3β (GSK3β) upon treatment with CBN, in the presence or not of distinct ECS-directed drugs. Overall, these results demonstrate that CBN modulates distinct ECS elements and exerts anti-inflammatory effects-remarkably via TRPV1-in human keratinocytes, thus holding potential for both therapeutic and cosmetic purposes.

Metabolite profiling and bioactivity assessment of cyanobacteria from the Azores reveals unique producers of cytotoxic and lipid reducing compounds

Cyanobacteria are a group of photosynthetic bacteria and a rich secondary metabolites source. The Bank of Algae and Cyanobacteria of the Azores (BACA) culture collection holds a significant number of strains, including many novel genera and species. 56 strains from freshwater, brackish, and thermal habitats were selected, and grown under standard conditions. Biomass was extracted with methanol, and cytotoxicity was assessed on two carcinoma cell lines, HepG2 and HCT116. The reduction of lipids was tested in zebrafish larvae, and in a steatosis model with fatty acid overloaded human liver cells. The cyanobacterial metabolome was analyzed by HR-ESI-LC-MS/MS and compared using CompareMS2. High similarities were observed in strains of the same genus when isolated from similar habitats, clustering in concordance to the taxonomical order, while no relation could be observed between strains from different genera originated from the same habitat. The extracts of Cyanobium sp. BACA0019, Pseudocalidococcus azoricus BACA0433 and Pegethrix atlantica BACA0077 reduced neutral lipids >40 % in zebrafish at 25 μg/mL, while from Symphyonema sp. BACA0090 and Aliinostoc sp. BACA0355 induced mortality. Lipid reduction in the steatosis model was observed in many strains, with significant results varying from 50 % to 100 %. Several strains reduced cell viability with the strongest effects from Scytonematopsis sp. BACA0005 (HepG2, 59.8 % and HCT116, 68.1 %), Aliinostoc sp. BACA0035 (HepG2, 43.3 %, and HCT116, 59.4 %) and Aliinostoc sp. BACA0355 (HepG2, 46.2 %, and HCT116, 75.5 %). The feature-based molecular networking identified several cluster of mass peaks related to the observed bioactivities. Chlorophyll derivatives and glycerolipids from Cyanobium sp. BACA0019, Pseudocalidococcus azoricus BACA0433 and Pegethrix atlantica BACA0077 were correlated with the reduction of lipids in zebrafish larvae, while several oligopeptides and fatty amides of Symphyonema sp. BACA0090 and Aliinostoc sp. BACA0355 with toxicity. Many clusters associated to the bioactivities remained unidentified, which may represent novel compounds, highlighting the chemodiversity of the BACA culture collection.

Gut microbiota‐directed dietary factors enhance exercise performance in mice

AbstractThis study investigated the effect of dietary interventions targeting gut microbiota on exercise performance in mice. Analysis of the gut microbiota of individuals with varying levels of physical activity revealed enrichment of Eubacterium rectale and Faecalibacterium prausnitzii in the active population. Through in vitro fecal fermentation experiments, dietary factor combinations that promote the abundance of these bacteria were identified. Dietary interventions, including E. rectale supplementation, FAG combination (gavage of Fructus Arctii extract, Agaricus blazei Murrill polysaccharides, and galactooligosaccharides mixture), and CFG combination (gavage of curcumin, Fructus Arctii extract, and galactooligosaccharides mixture), significantly improved mouse exercise performance, increased glycogen accumulation, regulated serum biochemical parameters, and increased short‐chain fatty acid and fatty acid amide levels in feces. Metagenomic sequencing revealed alterations in the composition of the gut microbiota. Fecal metabolome analysis highlighted changes in metabolites related to lipids, organic acids, nucleic acids, and carbohydrates. These findings suggest that E. rectale and dietary interventions positively affect exercise performance by modulating the gut microbiota and associated metabolites.

One Pot Synthesis of Alkyl Nitriles

A one-pot synthesis method to produce alkyl nitriles using the corresponding aliphatic carboxylic acid has been developed. The process involves treating the aliphatic acid with thionyl chloride to obtain the corresponding aliphatic acid chloride, which is then further treated with anhydrous ammonia gas to yield the respective aliphatic acid amide. The intermediate corresponding amide is dehydrated with thionyl chloride to obtain alkyl nitrile with a quantitative yield.

Targeting dysfunctional endocannabinoid signaling in a mouse model of Gulf War illness

Gulf War Illness (GWI) is a chronic disorder characterized by a heterogeneous set of symptoms that include pain, fatigue, anxiety, and cognitive impairment. These are thought to stem from damage caused by exposure under unpredictable stress to toxic Gulf War (GW) chemicals, which include pesticides, nerve agents, and prophylactic drugs. We hypothesized that GWI pathogenesis might be rooted in long-lasting disruption of the endocannabinoid (ECB) system, a signaling complex that serves important protective functions in the brain. Using a mouse model of GWI, we found that tissue levels of the ECB messenger, anandamide, were significantly reduced in the brain of diseased mice, compared to healthy controls. In addition, transcription of the Faah gene, which encodes for fatty acid amide hydrolase (FAAH), the enzyme that deactivates anandamide, was significant elevated in prefrontal cortex of GWI mice and brain microglia. Behavioral deficits exhibited by these animals, including heightened anxiety-like and depression-like behaviors, and defective extinction of fearful memories, were corrected by administration of the FAAH inhibitor, URB597, which normalized brain anandamide levels. Furthermore, GWI mice displayed unexpected changes in the microglial transcriptome, implying persistent dampening of homeostatic surveillance genes and abnormal expression of pro-inflammatory genes upon immune stimulation. Together, these results suggest that exposure to GW chemicals produce a deficit in brain ECB signaling which is associated with persistent alterations in microglial function. Pharmacological normalization of anandamide-mediated ECB signaling may offer an effective therapeutic strategy for ameliorating GWI symptomology.

Synthesis and quantitative structure–activity relationship of unsaturated fatty acid amide propyl dimethyl tertiary amines and their application in clean fracturing fluid thickener in low temperature environment

Solve the problem of freezing and blocking of clean fracturing fluid thickener during winter fracturing operations in the north, which is conducive to improving the efficiency of fracturing operations and oil and gas production rate. In this paper, four kinds of fatty acid amidopropyl dimethyl tertiary amine were successfully prepared and characterized with FT-IR and 1H NMR. Their acid values and Krafft temperature are discussed. The molecular structures of the four kinds of fatty acid amidopropyl dimethyl tertiary amine salts were optimized using Gaussian09 software, then their single point energies were calculated. A quantitative structure–property relationship (QSPR) model was established to predict Krafft temperature of the four kinds of fatty acid amidopropyl dimethyl tertiary amine salts. N-(3-(Dimethylamino)propyl)oleamide (PKO-O), (9Z,12Z)-N-(3-(dimethylamino)propyl)octadeca-9,12-dienamide (PKO-LO) were selected as the main agent. The optimal thickener formulation O1-8 and O2-1 were optimized by single factor experiment and orthogonal test respectively. O2-1 thickener has high low-temperature stability at −5 °C. The viscosity increase property, gel breaking property, rheological property, and viscoelasticity of the clean fracturing fluid obtained by cross-linking O1-8 with O2-1 thickener were evaluated and the properties of O1-8 thickener are better. The result shows that the O1-8 thickener basically meets the conditions of the winter fracturing construction site, and has more practical application significance.

Phenols, flavonoids and anthocyanins in Solanum lasiocarpum from Borneo: In vitro antioxidant activity and phytochemical profiling via LCMS Q-TOF

Phenols, flavonoids, and anthocyanins are compounds that reported play important roles in plant defence mechanism system. Antioxidant activity is mostly derived from these phytochemical groups, which have a wide range of pharmaceutical properties, including antimicrobial, antitumor, anti-inflammatory, antipyretic, anti-allergy, anti-fertility, hypoglycemic, anti-histamine, antioxidant, antiviral, analgesic, anti-ulcerogenic, nephroprotective, antidiabetic, immuno-secretory, cardiovascular, anti-platelet aggregation, antibacterial, anticancer, and hepatoprotective activities. However, these compounds in Solanum lasiocarpum from Borneo areas are remaining unclear. In this experiment, we performed comprehensive evaluation on effect of extraction solvents on phenols, flavonoids, and anthocyanin's contents and further on the scavenging activity (2,2-diphenyl-1-picrylhydrazyl-hydrate, DPPH; 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid), ABTS; and ferric-reducing antioxidant power, FRAP). High phenolic, flavonoid and anthocyanin contents be found in low polar solvent. Antioxidant assay showed acetone was higher activity with IC50 of 6.36 mg/mL compared to methanol (12.1 mg/mL) and hexane (17.8 mg/mL). Furthermore, liquid chromatography mass spectrometry quadrupole-time of flight (LCMS Q-TOF) mass spectrometer detected N-Acryloylglycine, butoctamide hydrogen succinate, eruberin B, emmotin A and N-Cyclohexanecarbonylpentadecylamine that important in natural polymers, serve as sleep disorders treatment agents, anti-fibrotic property, immunomodulatory activity, and act as differentiator between N-palmitoylethanolamine-hydrolyzing acid amidase (NPAA) compared to fatty acid amide hydrolase (FAAH), respectively. The limitation of this research is the assessment of antioxidant properties related to the polarity of the extraction solvent. Polar solvents may exhibit high scavenging activity, but phenolic compounds, flavonoids, and anthocyanins are found in higher concentrations in non-polar solvents. We encourage further investigation into phytochemical profiles due to the abundance from non-polar solvents.

Mitigation of cisplatin-induced acute kidney injury through oral administration of FAAH Inhibitor PF-04457845.

Fatty acid amide hydrolase (FAAH) serves as the primary enzyme responsible for degrading the endocannabinoid anandamide (AEA). Inhibition of FAAH, either through pharmacological means or genetic manipulation, can effectively reduce inflammation in various organs, including the brain, colon, heart, and kidneys. Infusion of a FAAH inhibitor into the kidney medulla has been shown to induce diuretic and natriuretic effects. FAAH knockout mice have shown protection against both post-ischemia reperfusion injury and cisplatin-induced acute kidney injury (AKI), although through distinct mechanisms. The present study was based on the hypothesis that pharmacological inhibition of FAAH activity could mitigate cisplatin-induced AKI, exploring potential renoprotective mechanism. Male wild type C57BL/6 were administered an oral gavage of a FAAH inhibitor (PF-04457845, 5mg/kg) or vehicle (10% PEG200+5% Tween80+normal saline) at 72, 48, 24, and 2 hours before and 24 and 48 hours after a single intraperitoneal injection of cisplatin (Cis, 25 mg/kg). Mice were euthanatized 72 hours after cisplatin treatment. Compared to vehicle-treated mice, PF-04457845-treated mice showed a decrease of cisplatin-induced plasma creatinine, blood urea nitrogen levels, kidney injury biomarkers (NGAL and KIM-1) and renal tubular damage. The renal protection from oral gavage of PF-04457845 against cisplatin-induced nephrotoxicity was associated with an enhanced AEA tone and reduced levels of DNA damage response biomarkers p53 and p21. Our work demonstrates that PF-04457845 effectively alleviates cisplatin-induced nephrotoxicity in mice, underscoring the potential of orally targeting FAAH as a novel strategy to prevent cisplatin nephrotoxicity. Significance Statement Oral administration of FAAH inhibitor, can reduce cisplatin-induced DNA damage response, tubular damages, and kidney dysfunction. Inactivation of FAAH could be a potential strategy to prevent cisplatin-induced nephrotoxicity.

Visible‐Light‐Promoted Cascade Radical Cyclization for Difluorochroman‐4‐ones via Electron Donor‐Acceptor Complexes

The research of electron donor‐acceptor complex has developed fast in the field of photochemistry. Herein, the green and efficient metal‐free visible‐light‐promoted synthesis of difluorochroman‐4‐ones has been achieved with 2‐(allyloxy)arylaldehyde and bromodifluoroacetamide, which is driven by noncovalent interactions between 2‐(allyloxy)arylaldehyde/N,N,N',N'‐tetramethylethylene diamine (TMEDA) and bromodifluoroacetamide/TMEDA. By precisely optimizing the electron donor and reaction solvent, a wide range of structurally diverse difluorochroman‐4‐ones, including aryl amide, aliphatic amide and ester groups, were obtained in up to 76% yields. This strategy offers the benefits of simple operation, good yields, high atomic economy and broad applicability, providing an essential complement to traditional approaches for the preparation of chroman‐4‐one skeletons without any transition metals, photocatalysts or oxidants.

Fabrication of a novel graphene oxide based magnetic nanocomposite and its usage as a highly effectual catalyst for the construction of N,N'-alkylidene bisamides.

At first, a novel graphene oxide-based magnetic nanocomposite namely Si-propyl-functionalized N 1,N 1,N 2,N 2-tetramethylethylenediamine-N 1,N 2-diium hydrogen sulfate anchored to graphene oxide-supported Fe3O4 (nano-[GO@Fe3O4@R-NHMe2][HSO4]) was fabricated. After full characterization of the nanocomposite, its catalytic performance was examined for the solvent-free construction of N,N'-alkylidene bisamides from aryl aldehydes (1 eq.) and primary aromatic and aliphatic amides (2 eq.), in which the products were acquired in short times (15-30 min) and high to excellent yields (89-98%). Nano-[GO@Fe3O4@R-NHMe2][HSO4] could be magnetically isolated form the reaction medium, and reused three times without remarkable loss of catalytic activity.