Tetrahydroxanthene-1,3(2H)-diones and Oxidized Hexadiene Derivatives from Uvaria leptopoda and Their Biological Activities.

The first phytochemical investigation of the twig extract of Uvaria leptopoda resulted in the isolation and identification of three new tetrahydroxanthene-1,3(2H)-diones, uvarialeptones A-C, two new oxidized hexadiene derivatives, uvarialeptols A and B, together with ten known compounds. Their structures were elucidated by spectroscopic techniques and mass spectrometry. Uvarialeptones A and B were unprecedented tetrahydroxanthene-1,3(2H)-dione dimers which exhibited a cyclobutane ring via [2 + 2] cycloaddition from uvarialeptone C and 9a-O-methyloxymitrone, respectively. The structure of uvarialeptone A was confirmed by X-ray diffraction analysis using Mo Kα radiation. Compound 3 inhibited NO production at an IC50 value of 6.7 ± 0.1 µM.

Natural xanthones as modulators of the Nrf2/ARE signaling pathway and potential gastroprotective agents.

Oxidative stress is implicated in the initiation, pathogenesis, and progression of various gastric inflammatory diseases (GID). The prevalence of these diseases remains a concern along with the increasing risks of adverse effects in current clinical interventions. Hence, new gastroprotective agents capable of inhibiting oxidative stress by modulating cellular defense systems such as the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway are critically needed to address these issues. A candidate to solve the present issue is xanthone, a natural compound that reportedly exerts gastroprotective effects via antioxidant, anti-inflammatory, and cytoprotective mechanisms. Moreover, xanthone derivatives were shown to modulate the Nrf2/ARE signaling pathway to counter oxidative stress in both in vitro and in vivo models. Thirteen natural xanthones have demonstrated the ability to modulate the Nrf2/ARE signaling pathway and have high potential as lead compounds for GID as indicated by their in vivo gastroprotective action-particularly mangiferin (2), α-mangostin (3), and γ-mangostin (4). Further studies on these compounds are recommended to validate the Nrf2 modulatory ability in relation to their gastroprotective action.

The Effects and Mechanisms of Xanthones in Alzheimer's Disease: A Systematic Review.

Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer's disease (AD). However, their underlying mechanisms in AD remain unclear. This study aimed to systematically review the effects and mechanisms of xanthones in cell culture and animal studies, gaining a better understanding of their roles in AD. A comprehensive literature search was conducted in the Medline and Scopus databases using specific keywords to identify relevant articles published up to June 2023. After removing duplicates, all articles were imported into the Rayyan software. The article titles were screened based on predefined inclusion and exclusion criteria. Relevant full-text articles were assessed for biases using the OHAT tool. The results were presented in tables. Xanthones have shown various pharmacological effects towards AD from the 21 preclinical studies included. Cell culture studies demonstrated the anti-cholinesterase activity of xanthones, which protects against the loss of acetylcholine. Xanthones exhibited neuroprotective effects by promoting cell viability, reducing the accumulation of ß-amyloid and tau aggregation. The administration of xanthones in animal models resulted in a reduction in neuronal inflammation by decreasing microglial and astrocyte burden. In terms of molecular mechanisms, xanthones prevented neuroinflammation through the modulation of signaling pathways, including TLR4/TAK1/NF-κB and MAPK pathways. Mechanisms such as activation of caspase-3 and -9 and suppression of endoplasmic reticulum stress were also reported. Despite the various neuroprotective effects associated with xanthones, there are limited studies reported on their underlying mechanisms in AD. Further studies are warranted to fully understand their potential roles in AD.

Synthesis of benzylated amine-substituted xanthone derivatives and their antioxidant and anti-inflammatory activities.

Oxidative stress and its constant companion, inflammation, play a critical part in the pathogenesis of many acute and chronic illnesses. The discovery of new multi-targeted drug candidates with antioxidant and anti-inflammatory properties is deemed necessary. Thus, a series of novel xanthone derivatives with halogenated benzyl (4b-4d, 4f-4h) and methoxylated benzyl groups (4e) attached to the butoxy amine substituent were synthesized in this study. The synthesized xanthone derivatives exhibited stronger antioxidant activity against H2 O2 scavenging than the standard drug, α-tocopherol, but weaker towards DPPH scavenging and ferrous ion chelation. Besides that, 4b-4d, 4f-4h demonstrated good anti-inflammatory activities through NO production inhibition towards lipopolysaccharide (LPS)-induced RAW 264.7 cells and showed 2-4 times stronger effects than the standard drug, diclofenac sodium. Moreover, compound 4b with two brominated benzyl groups attached to the butoxy amine substituent suppressed the production of pro-inflammatory cytokines, TNF-α and IL-1ß, significantly. Structure-activity relationship elucidated that the halogenated benzylamine substituent plays an important role in contributing the antioxidant and anti-inflammatory activities of xanthones. In summary, xanthone 4b was identified as a potential lead compound to be further developed into antioxidant and anti-inflammatory drugs. Thus, further studies on the related mechanisms of action of 4b are recommended.

Physicochemical and functional properties of Alcalase-extracted protein hydrolysate from oil palm leaves.

BACKGROUND: The oil palm tree produces 90% of wastes and the limited usage of these wastes causes a major disposal problem in the mills. Nevertheless, these by-products have a large amount of nutritional components. Thus, the present study aimed to determine the physicochemical and functional properties of protein hydrolysates (PH) from oil palm leaves (OPL) extracted using different concentrations of Alcalase (0-10%) at 2 h of hydrolysis time. RESULTS: Fourier transform infrared spectral analyses showed that the enzymatic hydrolysis altered functional groups of OPL where a secondary amine was present in the PH. Changes were also observed in the thermal stability where the enthalpy heat obtained for PH (933.93-1142.57 J g-1 ) was much lower than OPL (7854.11 J g-1 ). The results showed that the PH extracted by 8% Alcalase exhibited absolute zeta potential, as well as a high emulsifying activity index (70.64 m2  g-1 of protein) and emulsion stability index (60.58 min). Furthermore, this PH showed higher solubility (96.32%) and emulsifying properties compared to other PHs. It is also comparable with commercial plant proteins, indicating that 8% Alcalase is an optimum concentration for hydrolysis. CONCLUSION: In summary, the physicochemical and functional properties of PH extracted from OPL showed good functional properties, suggesting that it can be used as an alternative plant protein in food industries. © 2021 Society of Chemical Industry.

New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors.

A new series of 3-O-substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of them (5, 8, 11, 17, 19, 21-23, 26-28) exhibited significant effects with the IC50 values ranged 0.88 to 1.28 µM. The AChE enzyme kinetic study of 3-(4-phenylbutoxy)-9H-xanthen-9-one (23) and ethyl 2-((9-oxo-9H-xanthen-3-yl)oxy)acetate (28) showed a mixed inhibition mechanism. Molecular docking study showed that 23 binds to the active site of AChE and interacts via extensive π-π stacking with the indole and phenol side chains of Trp86 and Tyr337, besides the hydrogen bonding with the hydration site and π-π interaction with the phenol side chain of Y72. This study revealed that 3-O-alkoxyl substituted xanthone derivatives are potential lead structures, especially 23 and 28 which can be further developed into potent AChE inhibitors.

Impact of Storage Conditions on the Stability of Predominant Phenolic Constituents and Antioxidant Activity of Dried Piper betle Extracts.

The phenolic constituents in Piper betle are well known for their antioxidant potential; however, current literature has very little information on their stability under the influence of storage factors. Present study evaluated the stability of total phenolic content (TPC) and antioxidant activity together with individual phenolic constituents (hydroxychavicol, eugenol, isoeugenol and allylpyrocatechol 3,4-diacetate) present in dried Piper betle's extract under different storage temperature of 5 and 25 °C with and without light for a period of six months. Both light and temperature significantly influenced TPC and its corresponding antioxidant activity over time. More than 95% TPC and antioxidant activity was retained at 5 °C in dark condition after 180 days of storage. Hydroxychavicol demonstrated the best stability with no degradation while eugenol and isoeugenol displayed moderate stability in low temperature (5 °C) and dark conditions. 4-allyl-1,2-diacetoxybenzene was the only compound that underwent complete degradation. A new compound, 2,4-di-tert-butylphenol, was detected after five weeks of storage only in the extracts exposed to light. Both zero-order and first-order kinetic models were adopted to describe the degradation kinetics of the extract's antioxidant activity. Zero-order displayed better fit with higher correlation coefficients (R² = 0.9046) and the half-life was determined as 62 days for the optimised storage conditions (5 °C in dark conditions).

Cholinesterase Inhibitory Activities of Adamantyl-Based Derivatives and Their Molecular Docking Studies.

Adamantyl-based compounds are clinically important for the treatments of type 2 diabetes and for their antiviral abilities, while many more are under development for other pharmaceutical uses. This study focused on the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of adamantyl-based ester derivatives with various substituents on the phenyl ring using Ellman's colorimetric method. Compound 2e with a 2,4-dichloro electron-withdrawing substituent on the phenyl ring exhibited the strongest inhibition effect against AChE, with an IC50 value of 77.15 µM. Overall, the adamantyl-based ester with the mono-substituent at position 3 of the phenyl ring exhibited good AChE inhibition effects with an ascending order for the substituents: Cl < NO2 < CH3 < OCH3. Furthermore, compounds with electron-withdrawing groups (Cl and NO2) substituted at position 3 on their phenyl rings demonstrated stronger AChE inhibition effects, in comparison to their respective positional isomers. On the other hand, compound 2j with a 3-methoxyphenyl ring showed the highest inhibition effect against BChE, with an IC50 value of 223.30 µM. Molecular docking analyses were conducted for potential AChE and BChE inhibitors, and the results demonstrated that the peripheral anionic sites of target proteins were predominant binding sites for these compounds through hydrogen bonds and halogen interactions instead of hydrophobic interactions in the catalytic active site.

Anti-inflammatory, anti-cholinergic and cytotoxic effects of Sida rhombifolia.

CONTEXT: Sida (Malvaceae) has been used as a traditional remedy for the treatment of diarrhoea, malarial, gastrointestinal dysentery, fevers, asthma and inflammation. OBJECTIVES: This study evaluates the anti-inflammatory, cytotoxic and anti-cholinergic activities of Sida rhombifolia Linn. whole plant for the first time. MATERIALS AND METHODS: S. rhombifolia whole plant was extracted by n-hexane, ethyl acetate and methanol using Soxhlet apparatus. The plant extracts were evaluated for their antioxidant (DPPH, FIC and FRAP), anti-inflammatory (NO and protein denaturation inhibitions), cytotoxic (MTT) and anti-cholinesterase (AChE) properties in a range of concentrations to obtain IC50 values. GC-MS analysis was carried out on the n-hexane extract. RESULTS AND DISCUSSION: The ethyl acetate extract exhibited the most significant antioxidant activities by scavenging DPPH radicals and ferrous ions with EC50 of 380.5 and 263.4 µg/mL, respectively. In contrast, the n-hexane extract showed the strongest anti-inflammatory activity with IC50 of 52.16 and 146.03 µg/mL for NO and protein denaturation inhibition assays, respectively. The same extract also revealed the strongest effects in anti-cholinesterase and cytotoxic tests at the concentration of 100 µg/mL, AChE enzyme inhibition was 58.55% and human cancer cells, SNU-1 and Hep G2 inhibition was 68.52% and 47.82%, respectively. The phytochemicals present in the n-hexane extract are palmitic acid, linoleic acid and γ-sitosterol. CONCLUSIONS: The present study revealed that the n-hexane extract possessed relatively high pharmacological activities in anti-inflammation, cytotoxicity and anti-cholinesterase assays. Thus, further work on the detail mechanism of the bioactive phytochemicals which contribute to the biological properties are strongly recommended.

Synthesis and Crystallographic Insight into the Structural Aspects of Some Novel Adamantane-Based Ester Derivatives.

Adamantyl-based compounds are commercially important in the treatments for neurological conditions and type-2 diabetes, aside from their anti-viral abilities. Their values in drug design are chronicled as multi-dimensional. In the present study, a series of 2-(adamantan-1-yl)-2-oxoethyl benzoates, 2(a-q), and 2-(adamantan-1-yl)-2-oxoethyl 2-pyridinecarboxylate, 2r, were synthesized by reacting 1-adamantyl bromomethyl ketone with various carboxylic acids using potassium carbonate in dimethylformamide medium at room temperature. Three-dimensional structures studied using X-ray diffraction suggest that the adamantyl moiety can serve as an efficient building block to synthesize 2-oxopropyl benzoate derivatives with synclinal conformation with a looser-packed crystal packing system. Compounds 2a, 2b, 2f, 2g, 2i, 2j, 2m, 2n, 2o, 2q and 2r exhibit strong antioxidant activities in the hydrogen peroxide radical scavenging test. Furthermore, three compounds, 2p, 2q and 2r, show good anti-inflammatory activities in the evaluation of albumin denaturation.

Antiproliferative xanthone derivatives from Calophyllum inophyllum and Calophyllum soulattri.

Structure-activity relationships of eleven xanthones were comparatively predicted for four cancer cell lines after the compounds were subjected to antiproliferative assay against B-lymphocyte cells (Raji), colon carcinoma cells (LS174T), human neuroblastoma cells (IMR-32) and skin carcinoma cells (SK-MEL-28). The eleven chemical constituents were obtained naturally from the stem bark of Calophyllum inophyllum and Calophyllum soulattri. Inophinnin (1) and inophinone (2) were isolated from Calophyllum inophyllum while soulattrin (3) and phylattrin (4) were found from Calophyllum soulattri. The other xanthones were from both Calophyllum sp. and they are pyranojacareubin (5), rheediaxanthone A (6), macluraxanthone (7), 4-hydroxyxanthone (8), caloxanthone C (9), brasixanthone B (10) and trapezifolixanthone (11). Compound 3 was found to be the most cytotoxic towards all the cancer cell lines with an IC50 value of 1.25µg/mL while the simplest xanthone, compound 8 was inactive.

Topical Nanoemulsion Hydrogel Formulated from Supercritical Fluid Extracted Palm-Pressed Fiber Oil and Virgin Coconut Oil with Antioxidant and Antibacterial Effects.

Skincare industries are growing rapidly around the globe but most products are formulated using synthetic chemicals and organic solvent extracted plant extracts, thus may be hazardous to the users and incur higher cost for purification that eventually leads to phytonutrient degradation. Therefore, this study aimed to formulate a stable natural formulation with antioxidant and antimicrobial activities by using supercritical carbon dioxide (SC-CO 2 ) extracted palm-pressed fiber oil (PPFO) as an active ingredient with virgin coconut oil (VCO) as a formulation base. PPFO was extracted from fresh palm-pressed fiber (PPF) while VCO was from dried grated coconut copra using SC-CO 2 before being subjected to the analyses of physicochemical properties, phytonutrient content and biological activities including antioxidant and antimicrobial. The nanoemulgel formulations were then developed and examined for their stability through accelerated stability study for 3 months by measuring their pH, particle size, polydispersity index and zeta potential. The results showed that PPFO contained a high amount of phytonutrients, especially total carotenoid (1497 ppm) and total tocopherol and tocotrienol (2269 ppm) contents. The newly developed nanoemulgels maintained their particles in nano size and showed good stability with high negative zeta potentials. Sample nanoemulgel formulated with 3% PPFO diluted in VCO as effective concentration showed significantly stronger antioxidant activity than the control which was formulated from 3% tocopheryl acetate diluted in mineral oil, towards DPPH and ABTS radicals, with IC 50 values of 67.41 and 44.28 µL/mL, respectively. For the antibacterial activities, the sample nanoemulgel was found to inhibit Gram positive bacteria S. aureus and S. epidermidis growth but not the Gram negative strain E. coli. Overall, this study revealed the potential of SF-extracted PPFO as an active ingredient in the antioxidant topical formulations thus future study on in vitro skin cell models is highly recommended for validation.

Cytotoxicity and structure-activity relationships of xanthone derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora towards nine human cancer cell lines.

The cytotoxic structure-activity relationships among a series of xanthone derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora were studied. Eleven xanthone derivatives identified as mesuarianone (1), mesuasinone (2), mesuaferrin A (3), mesuaferrin B (4), mesuaferrin C (5), 6-deoxyjacareubin (6), caloxanthone C (7), macluraxanthone (8), 1,5-dihydroxyxanthone (9), tovopyrifolin C (10) and α-mangostin (11) were isolated from the three Mesua species. The human cancer cell lines tested were Raji, SNU-1, K562, LS-174T, SK-MEL-28, IMR-32, HeLa, Hep G2 and NCI-H23. Mesuaferrin A (3), macluraxanthone (8) and α-mangostin (11) showed strong cytotoxicities as they possess significant inhibitory effects against all the cell lines. The structure-activity relationship (SAR) study revealed that the diprenyl, dipyrano and prenylated pyrano substituent groups of the xanthone derivatives contributed towards the cytotoxicities.

Versatile Applications of Brewer's Spent Grain: Solid-State Fermentation and Nutritional Added Value.

Brewer's spent grain (BSG) is a major by-product in the beer-brewing process which contributes to 85% of the entire generated by-product in the brewing process. BSG is rich in proteins, and most of the malt proteins (74-78%) remain insoluble in BSG after the mashing process. Solid-state fermentation (SSF) is a promising bioprocess that enables microorganisms to survive in environments with minimal water and has shown to enhance the nutritional composition of BSG. In this review, the potential application of protein, amino acids (proline, threonine, and serine), phenolic contents, and soluble sugars (glucose, fructose, xylose, arabinose, and cellobiose) extracted from BSG by various microorganisms using SSF is explored. Incorporation of BSG into animal feed, human diets, and as a substrate for microorganisms are the prospects that could be implemented in the industrial scale. This review also discussed various advances to improve the fermentation yield such as symbiotic fermentation, the addition of nitrogen supplements, and an optimal mixture of the agro-industrial waste substrate. Future perspectives on SSF are also addressed to provide important ideas for immediate and future studies. However, challenges include optimizing SSF conditions and design of bioreactors, and operational costs must be addressed in the future to overcome current obstacles. Overall, this mini review highlights the potential benefits of BSG utilization and SSF in a sustainable way.

Synthesis of 1-hydroxy-3-O-substituted xanthone derivatives and their structure-activity relationship on acetylcholinesterase inhibitory effect.

This study focused on the synthesis of 1,3-dihydroxyxanthone (1) and its new derivatives with alkyl (2a-2f), alkenyl (2 g-2k), alkynyl (2 l-2n), and alkylated phenyl (2o-2r) groups at C3 position. The structures of these compounds were confirmed by MS, NMR, and FTIR spectroscopic data. All the substituted xanthones (2a-2r) showed significantly stronger acetylcholinesterase (AChE) inhibitory activities than 1. Compounds 2g and 2j exhibited the strongest activities with the IC50 values of 20.8 and 21.5 µM and their enzyme kinetic analyses indicated a mixed-mode inhibition. Molecular docking study revealed that 2g binds favourably to the active site of AChE via π-π stacking and hydrogen bonding from the xanthone ring, in addition to π-alkyl interaction from the substituent group. These xanthone derivatives are potential lead compounds to be further developed into Alzheimer's disease drugs.

Mesua beccariana (Clusiaceae), a source of potential anti-cancer lead compounds in drug discovery.

An investigation on biologically active secondary metabolites from the stem bark of Mesua beccariana was carried out. A new cyclodione, mesuadione, along with several known constituents which are beccamarin, 2,5-dihydroxy-1,3,4-trimethoxy anthraquinone, 4-methoxy-1,3,5-trihydroxyanthraquinone, betulinic acid and stigmasterol were obtained from this ongoing research. Structures of these compounds were elucidated by extensive spectroscopic methods, including 1D and 2D-NMR, GC-MS, IR and UV techniques. Preliminary tests of the in vitro cytotoxic activities of all the isolated metabolites against a panel of human cancer cell lines Raji (lymphoma), SNU-1 (gastric carcinoma), K562 (erythroleukemia cells), LS-174T (colorectal adenocarcinoma), HeLa (cervical cells), SK-MEL-28 (malignant melanoma cells), NCI-H23 (lung adenocarcinoma), IMR-32 (neuroblastoma) and Hep-G2 (hepatocellular liver carcinoma) were carried out using an MTT assay. Mesuadione, beccamarin, betulinic acid and stigmasterol displayed strong inhibition of Raji cell proliferation, while the proliferation rate of SK-MEL-28 and HeLa were strongly inhibited by stigmasterol and beccamarin, indicating these secondary metabolites could be anti-cancer lead compounds in drug discovery.

Phylattrin, a new cytotoxic xanthone from Calophyllum soulattri.

Our continuing studies on secondary metabolites from the stem bark of Calophyllum soulattri has led to the isolation of another new diprenylated xanthone, phylattrin (1), in addition to five other xanthones and two common sterols. The xanthones are soulattrin (2), caloxanthone C (3), macluraxanthone (4), brasixanthone B (5) and trapezifolixanthone (6) while the sterols are stigmasterol (7) and ß-sitosterol (8). The structures of these compounds were determined on the basis of spectroscopic analyses such as 1D and 2D-NMR, HRESIMS, IR and UV. Compounds 1-7 exhibited moderate cytotoxic activities against SNU-1, HeLa, Hep G2, NCI-H23, K562, Raji, LS174T, IMR-32 and SK-MEL-28 cells.

rac-[3-Hydroxy-6,9-dimethyl-6-(4-methylpent-3-en-1-yl)-6a,7,8,9,10,10a-hexahydro-6H-1,9-epoxybenzo[c]chromen-4-yl](phenyl)methanone.

The title compound congestiflorone, C(28)H(32)O(4), which was isolated from the stem bark of Mesua congestiflora, consists of a benzophenone skeleton with two attached pyran rings to which a cyclo-hexane ring and a C6 side chain are bonded. The benzene ring is significantly distorted from planarity (r.m.s. deviation = 0.0007 Å) due to the constraints imposed by junctions with the two pyran rings. The cyclo-hexane ring is in a chair conformation, one pyran ring is in a boat conformation, while the other is a distorted chair. The phenyl and benzene rings make a dihedral angle of 55.85 (9)°. An intra-molecular O-H⋯O hydrogen bond is observed. In the crystal, mol-ecules are linked via C-H⋯O inter-actions.

Retinoids as anti-cancer agents and their mechanisms of action.

Retinoids (vitamin A) have been reported extensively for anti-cancer properties due to their high receptor-binding affinities and gene regulation abilities. However, the anti-cancer potential of retinoids has not been reviewed in recent years. Thus, this review focused on the anti-cancer effects of retinoids and their synergistic effects with other drugs, together with their mechanisms of action in different types of cancers reported in the past five years. The retinoids were well studied in breast cancer, melanoma, and colorectal cancer. Synthetic retinoids have shown higher selectivity, stronger effectiveness, and lower toxicity than endogenous retinoids. Interestingly, the combination treatment of endogenous retinoids with chemotherapy drugs showed enhanced anti-cancer effects. The mechanisms of action reported for retinoids mainly involved the RAR/RXR signaling pathway. However, limited clinical studies were conducted in recent years. Thus, retinoids which are highly potential anti-cancer agents are worth further study in clinical, especially as a combination therapy with chemotherapy drugs.

Protective Effects of Alternanthera sessilis Ethanolic Extract against TNF-α or H2O2-Induced Endothelial Activation in Human Aortic Endothelial Cells.

Activation of the endothelium has been shown to contribute to the early stage of vascular diseases such as atherosclerosis and hypertension. In endothelial activation, excess reactive oxygen species (ROS) production and increased expression of cell adhesion molecules cause an increase in vascular permeability. Alternanthera sessilis (L.) R. Br. is an edible traditional herbal plant, which has previously been shown to possess antioxidant and anti-inflammatory effects. However, the effect of A. sessilis on the activation of human aortic endothelial cells (HAECs) remains unknown. This study aimed to investigate the effects of A. sessilis on endothelial permeability, vascular cell adhesion-1 (VCAM-1) expression, production of ROS and hydrogen peroxide (H2O2), and superoxide dismutase (SOD) and catalase (CAT) activities. The viability of HAECs was first determined using the MTT viability assay. The effect of A. sessilis on endothelial permeability was examined using the FITC-dextran permeability assay. Besides, enzyme-linked immunosorbent assay (ELISA) was done to assess soluble VCAM-1 (sVCAM-1) expression. The production of ROS and H2O2 was studied using 2',7'-dichlorodihydrofluorescein diacetate (H2-DCFDA) and Amplex Red fluorescent dyes, respectively. SOD and CAT activities were also measured using commercial kits. Our results showed that 25-200 µg/mL of A. sessilis ethanolic extract did not cause significant death in HAECs. A. sessilis at 200 µg/mL significantly inhibited TNF-α-induced hyperpermeability of HAECs. However, A. sessilis did not reduce increased VCAM-1 expression induced by TNF-α. A. sessilis also significantly reduced TNF-α-induced increased ROS production, but not H2O2 production. Furthermore, 100 µM of H2O2 decreased both SOD and CAT activities in HAECs at 2 h. A. sessilis ethanolic extract dramatically increased both reduced SOD and CAT activities caused by H2O2. The liquid chromatography-mass spectrometry (LC-MS) analysis of A. sessilis ethanolic extract demonstrated the presence of arachidonic acid, azadirachtin, astaxanthin, flavanole base + 3O, 2Prenyl, and vicenin 2, while the gas chromatography-mass spectrometry (GC-MS) analysis showed that the extract contains 1,3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one, 3-deoxy-d-mannoic lactone, 4-pyrrolidinobenzaldehyde, and n-hexadecanoic acid. In conclusion, our findings suggest that A. sessilis ethanolic extract protects against endothelial hyperpermeability and oxidative stress elicited by pro-inflammatory or prooxidant stimulus. This study reveals a therapeutic potential of A. sessilis in preventing endothelial activation, which is a key event in early atherosclerosis.