Cannabidiol (CBD), a phytocannabinoid, has been reported to have anti-inflammatory effects associated with NLRP3 inflammasome activation, but its mechanism of anti-inflammasome action remains unclear. Herein, we report CBD's effect on activation and modulation P2X7, an activation-related receptor, in human THP-1 monocytes. CBD (0.1, 1, 10 μM) exerted activity LPS-nigericin-stimulated monocytes by reducing media IL-1β concentration (by 63.9%, 64.1%, 83.1%, respectively), which was similar the...

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are two cholinergic enzymes catalyzing the reaction of cleaving acetylcholine into acetate choline at neuromuscular junction. Abnormal hyperactivity AChE BChE can lead to deficiency, which is associated with several neurological disorders including cognitive decline memory impairments. Preclinical studies support that some cannabinoids cannabidiol (CBD) tetrahydrocannabinol (THC) may exert pharmacological effects on system, but it...

Precursors of advanced glycation endproducts, namely, reactive carbonyl species (RCSs), are aging biomarkers that contribute to cell death. However, the impact RCSs on ferroptosis—an iron-dependent form death—in skin cells remains unknown. Herein, we constructed a cellular model (with human keratinocyte; HaCaT cells) evaluate cytotoxicity combinations (including glyoxal; GO and methyglyoxal; MGO) erastin (a ferroptosis inducer) using bioassays (measuring lipid peroxidation iron content)...

Skin cells are susceptible to oxidative stress and various types of cell death, including an iron-dependent form known as ferroptosis. Cannabidiol (CBD) can protect skin against stress, but whether this is attributed the inhibition ferroptosis unknown. Herein, we evaluated anti-ferroptotic effect CBD in human keratinocytes using biochemical assays (radical scavenging iron chelating) cell-based models (for lipid peroxidation intracellular iron). CBD's was further characterized by proteomic...

Diets rich in fats are linked to elevated systemic inflammation, which augments the progression of inflammatory-related disorders including non-alcoholic fatty liver disease (NAFLD) and neurodegenerative diseases. A phenolic-enriched pomegranate fruit extract (PE) was investigated for its hepatoprotective anti-inflammatory effects male C57BL/6 mice fed either a high-fat diet or standard rodent with without 1% PE 12 weeks. Mouse livers hippocampi were evaluated expression genes associated...

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) main protease (Mpro) inhibitors are considered as potential treatments for disease 2019, and dietary polyphenols show promise in SARS-CoV-2 Mpro inhibition based on silico studies. In the present study, we utilize a combination of biochemical-, surface plasmon resonance-, docking-based assays to evaluate binding affinities series tannins their gut microbial metabolites Mpro. The tested compounds (2–50 μM) were hydrolyzable tannins,...

The disruption of the PD-1/PD-L1 interaction is a promising strategy for cancer immunotherapy. Reliable screening platforms are essential evaluating efficacy inhibitors. A previously established human blockade assay utilizing Surface Plasmon Resonance (SPR) technology (first-generation inhibitor SPR platform) demonstrated results comparable to those obtained through Homogeneous Time-Resolved Fluorescence (HTRF) and cell-based assays, with potential large-scale screening. Herein, an optimized...

Objectives: Alzheimer's disease (AD) is a growing global health crisis exacerbated by increasing life span and an aging demographic. Convergent lines of evidence, including genome-wide association studies, strongly implicate neuroinflammation in the pathogenesis AD. Several dietary agents, phenolic-rich foods, show promise for prevention and/or management AD, which large part, has been attributed to their anti-inflammatory effects. We previously reported that food-grade phenolic-enriched...

The secondary metabolite content of cranberry fruits can vary with cultivar and environmental factors, which may in turn impact their potential biological activities. To evaluate the influence composition on anti-inflammatory activity, were collected from two major U.S. growing regions. Eight extracts these prepared, analyzed for phytochemical composition, evaluated effects human monocytes (THP-1 cells). varied widely polyphenol triterpenoid content. All able to reduce lipopolysaccharide...

The replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by its main protease (Mpro), which a plausible therapeutic target for disease 2019 (COVID-19). Although numerous in silico studies reported potential inhibitory effects natural products including cannabis and cannabinoids on SARS-CoV-2 Mpro, their anti-Mpro activities are not well validated biological experimental data. Herein, library minor belonging to several chemotypes tetrahydrocannabinols,...

Rutaevin is one of the major bioactive constituents isolated from Evodia rutaecarpa, a well-known herbal medicine that has been widely prescribed for treatment gastrointestinal disorders in China. However, oral administration rutaevin shown to cause hepatotoxicity mice. Bioactivation was suggested be involved rutaevin-induced hepatotoxicity. The aim this study investigate bioactivation rat and human liver microsomes fortified with NADPH. metabolized into reactive intermediate...

Inhibitors targeting kynurenine-3-monooxygenase (KMO), an enzyme in the neurotoxic kynurenine pathway (KP), are potential therapeutics for KP metabolites-mediated neuroinflammatory and neurodegenerative disorders. Although phytochemicals from Cannabis (C. sativa L.) have been reported to show modulating effects on enzymes involved metabolism, inhibitory of C. compounds, including phytocannabinoids non-phytocannabinoids (i.e., cannflavin A; CFA), KMO remain unknown. Herein, CFA (purified hemp...

Glucitol-core containing gallotannins (GCGs) from the red maple (Acer rubrum) species have been reported to exhibit skin beneficial activities but their inhibitory effects on elastase remain unclear. Herein, we evaluated a series of GCGs for anti-elastase activity, permeability, and cytoprotective in human keratinocytes HaCaT cells. GCGs' were enhanced as number galloyl groups increased, which may be attributed formation more stable protein–ligand complexes. In addition, predicted moderate...

Oleuropein (OLE) and hydroxytyrosol (HT) are dietary polyphenols with skin beneficial effects but their on skin-ageing-related enzymes not clear. Herein, we evaluated inhibitory elastase collagenase. OLE HT (62.5-1 000 μM) showed moderate anti-elastase anti-collagenase (5.1-26.3%, 5.8-12.2% 12.6-31.0%, 11.6-31.9% inhibition, respectively). Combinations of (1:1 ratio) exerted synergistic elastase, which were supported by combination index (CI), kinetic assay computational docking. Moreover,...

Our group has previously reported on the phytochemical composition and biological activities of a phenolic-enriched maple syrup extract (MSX), which showed promising anti-inflammatory effects in several disease models including diabetes Alzheimer's disease. However, efficacious doses MSX its molecular targets involved are not fully elucidated. Herein, efficacy peritonitis mouse model was evaluated dose-finding study underlying mechanisms were explored using data-independent acquisition (DIA)...

Cannabis and its major cannabinoid cannabidiol (CBD) are reported to exhibit anticancer activity against skin tumors. However, the cytotoxic effects of other minor cannabinoids synthetic CBD derivatives in melanoma not fully elucidated. Herein, antiproliferative a panel phytocannabinoids was screened murine (B16F10) human (A375) cells. most natural with respective IC50 28.6 51.6 μM. Further assessment cytotoxicity B16F10 cells identified two bipiperidinyl group-bearing (22 34) enhanced (IC50...

Blockade of the programmed cell death protein 1 (PD-1)/PD-ligand (PD-L1) axis is a promising strategy for cancer immunotherapy. Although antibody-based PD-1/PD-L1 inhibitors have shown remarkable results in clinical studies, their inherent limitations underscore significance developing novel inhibitors. Small molecule several advantages over inhibitors, including favorable tumor penetration and oral bioavailability, fewer side effects, easier administration, preferred biological half-life,...

Phenolics enriched pomegranate fruit (Pomella

Our laboratory has established a comprehensive program to investigate the phytochemical composition and nutritional/medicinal properties of phenolic-enriched maple syrup extract (MSX). Previous studies support MSX's therapeutic potential in diverse disease models, primarily through its anti-inflammatory effects. We recently demonstrated ability regulate inflammatory signaling pathways modulate markers proteins lipopolysaccharide (LPS)-induced peritonitis mouse model. However,...

Background: The structure modification of steroids is commonly used to change the biological activity in medicinal chemistry. In recent years, it has been found that some derivatives derived from structural cholesterol display good inhibitory against tumor cell proliferation vitro. Methods: Using as starting material, different types B-norcholesterol-6-amide were synthesized by reaction 6-carboxyl-B-norcholesterol with alkyl amines or 6-amino-B-norcholesterol acyl chlorides. compounds on...

Phenylahistin is a naturally occurring marine product with diketopiperazine structure that can bind to the colchicine site of microtubulin as possible anticancer agent. To develop more potent microtubule inhibitors, novel phenylahistin derivatives were designed and synthesized based on co-crystal complexes microtubulin. We established focused library imidazole-type molecules for introduction different groups C-ring A-ring phenylahistin. Structure–activity relationship studies indicated...

Abstract Background Lung cancer possesses high mortality rate and tolerances to multiple chemotherapeutics. Natural Borneol (NB) is a monoterpenoid compound that found facilitate the bioavailability of drugs. In this study, we attempted investigate effects NB on chemosensitivity in A549 cells try elucidate its therapeutic target. Methods The was examined by MTT assay. mechanism studies were evaluated flow cytometry western blotting Surface plasmon resonance (SPR) LC-MS combined analysis...