Evaluation of selected natural sesquiterpenes as sensitizing agents of ß-lactam-resistant bacterial strains.

AIMS: To evaluate the capacity of fourteen sesquiterpenes to enhance the action of known antibiotics against two ß-lactam resistant strains, and to determine a possible mechanism of antibiotic sensitization by assessing their ability to inhibit a ß-lactamase enzyme. METHODS AND RESULTS: The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of ß-lactams cefuroxime (CEFM) and cefepime (CPM) against Staphylococcus aureus 23MR and Escherichia coli 82MR strains in the absence and presence of subinhibitory concentrations of fourteen natural sesquiterpenes. (1R,4R)-4H-1,2,3,4-tetrahydro-1-hydroxycadalen-15-oic acid (5), xerantolide (8), estafiatin (11), and ambrosin (12) exhibited the best sensitizing effects in both strains. These compounds were able to reduce the MIC of CEFM by 2-fold (from 15.0 to 7.5 µg/mL) and CPM by 15-fold (from 0.9 to 0.06 µg/mL) in S. aureus 23MR. For E. coli 82MR, the MIC of CEFM was reduced up to 8-fold (from 120.0 to 15.0 µg/mL). In this strain, the activity of 8 and 11 surpassed that of clavulanic acid (positive reference), which reduced the MIC of CEFM from 120.0 to 60.0 µg/mL. To elucidate a possible mechanism of antibiotic sensitization, molecular docking studies were conducted with ß-lactamases. These studies revealed an affinity with the enzymes (energies > -4.93 kcal/mol) by the formation of hydrogen bonds with certain conserved amino acid residues within the active sites. However, the in vitro results indicated only marginal inhibition, with percentages <50%. CONCLUSIONS: The bioevaluations indicate that nine of fourteen sesquiterpenes enhance the action of CEFM and CPM against the ß-lactam resistant strains, and these compounds displayed moderate activity as inhibitors of ß-lactamase.

Larvicidal Activity against Spodoptera frugiperda of some Constituents from two Diospyros Species. In silico Pesticide-likeness Properties, Acetylcholinesterase Activity and Molecular Docking.

This report informs for the first time the chemical constituents of Diospyros xolocotzii and Diospyros digyna, the pesticidal and the acetylcholinesterase (AChE) inhibition potential of some compounds calculated by in silico approaches, the larvicidal activity against Spodoptera frugiperda of available compounds, the AChE inhibition of selected compounds, and the results of the molecular docking of the most active ones with this receptor. From the aerial parts of D. xolocotzii were isolated pentacyclic triterpenes (1-4, 6, 10, 11-13), phytosterols (15-17), and isodiospyrin (18), whereas the analysis of aerial parts of D. digyna conducted to the isolation of pentacyclic triterpenes (4, 5, 7-9, 11-14), (4S)-shinanolone (19), and scopoletin (20). For comparison purposes, origanal (21) was chemically prepared from 11. The in silico analysis showed that the tested compounds have pesticide potential. The larvicidal activities of 11>13>12 indicated that the increase of the oxidation degree at C-28 increases their bioactivity. Compounds 11 and 21 presented the higher inhibition in the acetylcholinesterase assay, and the higher binding energies, and for the interactionswith AChE by molecular docking. Both Diospyros species are sources of triterpenes with pesticidal potential and the molecular changes in lupane triterpenes correlate with the observed bioactivity and molecular docking.

The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin.

Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

The Homoleptic Curcumin-Copper Single Crystal (ML2): A Long Awaited Breakthrough in the Field of Curcumin Metal Complexes.

The first single crystal structure of the homoleptic copper (II) ML2 complex (M=Cu (II), L = curcumin) was obtained and its structure was elucidated by X-ray diffraction showing a square planar geometry, also confirmed by EPR. The supramolecular arrangement is supported by C-H···O interactions and the solvent (MeOH) plays an important role in stabilizing the crystal packing Crystallinity was additionally assessed by XRD patterns. The log P value of the complex (2.3 ± 0.15) was determined showing the improvement in water solubility. The cytotoxic activity of the complex against six cancer cell lines substantially surpasses that of curcumin itself, and it is particularly selective against leukemia (K562) and human glioblastoma (U251) cell lines, with similar antioxidant activity to BHT. This constitutes the first crystal structure of pristine curcumin complexed with a metal ion.

Synthesis, biological evaluation, molecular docking studies and In-silico ADMET evaluation of pyrazines of pentacyclic triterpenes.

The semisynthesis of novel derivatives of lupeyl palmitate and 3ß-palmitoyloxy-olean-12-ene by introduction of a pyrazine at C-2 / C-3 and modifications of the relatively unexplored C-30 position of lupeol derivatives was conducted, and their cytotoxic and anti-inflammatory activities were evaluated. The derivatives 7, 10 and 11 significantly inhibited the tumor cell lines U251, K562, HCT-15, MCF-7 and SKLU-1, and compounds 7 and 11 were more active (IC50 25.4 ± 2.0 µM and 7.1 ± 0.4 µM, respectively) than the positive control (etoposide (IC50 31.5 ± 2.2 µM) in the tumor line PC-3. Introduction of the pyrazine at C-2 / C-3 in compounds 1 and 2 or modification at C-30 of compound 1 decreased the anti-inflammatory activity in the TPA-induced mouse ear edema. Following the results of the PASS online evaluation of the potential biological activity of the natural compounds and their derivatives, the inhibition of pNF-κB translocation to the prostate cancer (PC-3) cell nucleus was investigated and the binding mode of compounds 7, 10 and 11 with the human NF-κB receptor was explored by a molecular docking study. These derivatives bound directly or close to the amino acids that form the DNA recognition site. The ADMET physicochemical parameters of the fifteen compounds were further analyzed in silico using Molinspiration calculations indicating the potential of compounds 7, 10 and 11 for further investigation.

Multicomponent synthesis and preliminary anti-inflammatory activity of lipophilic diphenylamines.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are some of the most prescribed medications for pain but the incidence of adverse effects -especially during chronic treatment- points out the requirement of new analgesics. In this study, we showed an efficient two-steps synthesis of diphenylamine-containing dipeptides consisting of a multicomponent process followed by a Buchwald-Hartwig cross-coupling reaction. We prepared 16 diphenylamine derivatives and evaluated their in vivo anti-inflammatory activity through an ear edema model using 12-O-tetradecanoylpholbol-13-acetate. Furthermore, the toxicity of the more potent compounds in the Artemia salina model and their cell viability using murine RAW 264.7 cells is reported. The fluorinated compound 10k becomes a reliable candidate since it reduced the TPA-induced edema to 92%, lacked cytotoxicity against murine macrophages, and had minimal toxicity in Artemia salina.

Hopane-type triterpenes from Cnidoscolus spinosus and their bioactivities.

Chemical investigation of the aerial parts of Cnidoscolus spinosus resulted in the isolation of relatively infrequent hopane-type triterpenes, 3ß-acetoxy-hop-22(29)-ene (1), first reported here as natural product, together with 3-oxo-hop-22(29)-ene (2), and 3ß-hydroxy-hop-22(29)-ene (3). ß-Amyrin palmitate and three phytosterols were also characterized. The structures of the compounds were established using spectroscopic methods, and those of 1 and 2 were confirmed by crystallographic analysis. Selected biological activities for the isolated hopane-type triterpenes were tested through a series of assays for determining the cytotoxic, anti-inflammatory, α-glucosidase inhibition and antiparasitic activities. Compounds 1-3 did not show cytotoxic activity, compound 1 displayed an important inhibitory effect in the mouse ear induced inflammation assay, and significantly inhibited the yeast α-glucosidase activity in vitro and in silico. Additionally, compounds 2 and 3 showed marginal activities against Trypanosoma cruzi and Leishmania mexicana. Therefore, the bioactivities of hopane-type triterpenes deserve further investigation, particularly their anti-inflammatory properties.

Recognition of antioxidants and photosensitizers in Dyssodia pinnata by EPR spectroscopy.

INTRODUCTION: Previous studies report the isolation mainly of terthiophene derivatives and flavonoids from Dyssodia species. Terthiophenes are known as photosensitizers by their capacity to generate singlet oxygen (1 O2 ), and flavonoid antioxidant activity is recognized. These opposite properties could represent interesting options in photodynamic therapy. OBJECTIVE: To determine the antioxidant and photosensitizer activities of extracts and isolates of Dyssodia pinnata by electron paramagnetic resonance (EPR). METHODOLOGY: Extracts and isolates were evaluated as antioxidants by the interactions with copper ion (Cu2+ ) observed in EPR, and by the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and the thiobarbituric reactive substances (TBARS) methods. Their abilities as 1 O2 producers were also estimated by EPR. RESULTS: Terthiophenes were obtained from hexane (DPH) and acetone (DPA) extracts, and flavonoids from DPA and methanol (DPM) extracts. The interaction with Cu2+ of extracts and isolated compounds of Dyssodia pinnata showed two effects in EPR: reduction and chelation; flavonoids exhibited both effects, while terthiophenes showed only reduction. DPA, DPM, and flavonoids were active in DPPH and TBARS assays. Quercetagetin-7-O-ß-glucoside showed the highest antioxidant and chelating activities, 3-glycosidated flavonoids were less active. Upon irradiation extracts and terthiophenes induced 1 O2 formation. CONCLUSION: Flavonoid reducing activity on Cu2+ and free radical scavenging capacity were related to the number of hydroxy groups and to the conjugation between the B and C rings. All tested flavonols showed a major complex with Cu2+ , with the most probable site of chelation between the 5-hydroxy and 4-oxo groups. Extracts and terthiophene derivatives showed photosensitizer activity. Thus, EPR is useful to evaluate free radical scavenging and pro-oxidant properties.

Goat's Milk Intake Prevents Obesity, Hepatic Steatosis and Insulin Resistance in Mice Fed A High-Fat Diet by Reducing Inflammatory Markers and Increasing Energy Expenditure and Mitochondrial Content in Skeletal Muscle.

Goat's milk is a rich source of bioactive compounds (peptides, conjugated linoleic acid, short chain fatty acids, monounsaturated and polyunsaturated fatty acids, polyphenols such as phytoestrogens and minerals among others) that exert important health benefits. However, goat's milk composition depends on the type of food provided to the animal and thus, the abundance of bioactive compounds in milk depends on the dietary sources of the goat feed. The metabolic impact of goat milk rich in bioactive compounds during metabolic challenges such as a high-fat (HF) diet has not been explored. Thus, we evaluated the effect of milk from goats fed a conventional diet, a conventional diet supplemented with 30% Acacia farnesiana (AF) pods or grazing on metabolic alterations in mice fed a HF diet. Interestingly, the incorporation of goat's milk in the diet decreased body weight and body fat mass, improved glucose tolerance, prevented adipose tissue hypertrophy and hepatic steatosis in mice fed a HF diet. These effects were associated with an increase in energy expenditure, augmented oxidative fibers in skeletal muscle, and reduced inflammatory markers. Consequently, goat's milk can be considered a non-pharmacologic strategy to improve the metabolic alterations induced by a HF diet. Using the body surface area normalization method gave a conversion equivalent daily human intake dose of 1.4 to 2.8 glasses (250 mL per glass/day) of fresh goat milk for an adult of 60 kg, which can be used as reference for future clinical studies.

Structural Elucidation of Malonylcommunol and 6ß-Hydroxy-trans-communic Acid, Two Undescribed Diterpenes from Salvia cinnabarina. First Examples of Labdane Diterpenoids from a Mexican Salvia Species.

The aerial parts of Salvia cinnabarina afforded two undescribed labdane diterpenoids 1 and 2 (malonylcommunol and 6ß-hydroxy-trans-communic acid) along with two known labdane diterpenoids, trans-communic acid (3) and trans-communol (4). Additionally, seven known metabolites were also isolated; two isopimarane diterpenoids 5 and 6, two sesquiterpenoids identified as ß-eudesmol (7) and cryptomeridiol (8), and three aromatic compounds identified as phthalic acid (9), a mixture of tyrosol fatty acid esters (10) and the flavone salvigenine (11). While compounds compounds 1-3 showed significant inhibition of yeast α-glucosidase, compounds 2, 3 and 7 had no anti-inflammatory activity in the edema model induced by TPA. This paper is not only the first report on a wild population of Salvia cinnabarina, but also of the presence of labdane-type diterpenoids in a Mexican Salvia sp.

Synthesis of diphenylamine macrocycles and their anti-inflammatory effects.

A collection of fourteen diphenylamine macrocyclic derivatives containing a peptide chain with different substituents was synthesized using a protocol of two Ugi four component reactions (Ugi-4CR) and a Buchwald-Hartwig macrocyclization. Their anti-inflammatory effects were assayed with an ear edema model using 12-O-tetradecanoylphorbol-13-acetate, while the activity of myeloperoxidase was determined to evaluate the index of leukocyte infiltration. Compound 5e had an ID50 of 0.18 µM per ear with a potency higher than that of the reference drugs indomethacin and celecoxib (0.24 and 0.91 µM per ear, respectively). Moreover, the cytotoxicity of the macrocycles was determined in two healthy cell lines, showing a low percentage of toxicity.

Labdanes, Withanolides, and Other Constituents from Physalis nicandroides.

Chemical investigation of the aerial parts (except fruits and calixes) of Physalis nicandroides var. attenuata led to the isolation of a series of new labdane-type diterpenoids, including the closely related compounds 1-3, the labdane glucosides 4 and 5, a mixture of the epimeric alcohols 6 and 7, and one labdanetriol, isolated as its tri-O-acetyl derivative 9. In addition, three new withanolides (14-16) and six known compounds were isolated. The structures of these compounds were elucidated by analysis of their spectroscopic data and chemical transformations, and those of compounds 1, 4, and 16 were confirmed by X-ray diffraction analysis of the natural product (1) and of the corresponding acetyl derivatives 4a and 16a. Fourteen of these compounds were assayed for their in vitro inhibitory activity against yeast α-glucosidase and acetylcholinesterase enzymes. The results were negative in both cases, except for compound 3a that marginally inhibited the activity of acetylcholinesterase with an IC50 value of 64.4 µM.

Structure and Absolute Configuration of Abietane Diterpenoids from Salvia clinopodioides: Antioxidant, Antiprotozoal, and Antipropulsive Activities.

The aerial parts of Salvia clinopodioides afforded abietanes 1a, 2a, and 3 (clinopodiolides A-C), two of which possess an unusual lactol moiety at C-19-C-20, together with an icetexane named clinopodiolide D (4a). Their structures were established by spectroscopic means, mainly 1H and 13C NMR, including 1D and 2D homo- and heteronuclear experiments. The antioxidant, antiprotozoal, and antidiarrheal effects of the isolates were evaluated. Compounds 2a and 3 showed better effects than α-tocopherol in the inhibition of lipid peroxidation with IC50 (µM) = 5.9 ± 0.1 and 2.7 ± 0.2, respectively, and moderate activity in the DPPH assay. All tested compounds showed moderate antiamoebic and antigiardial activity, as well as a good antipropulsive effect.

A New Family of Homoleptic Copper Complexes of Curcuminoids: Synthesis, Characterization and Biological Properties.

We report herein the synthesis and crystal structures of five new homoleptic copper complexes of curcuminoids. The scarcity of reports of homoleptic complex structures of curcuminoids is attributed to the lack of crystallinity of such derivatives, and therefore, their characterization by single crystal X-ray diffraction is rare. The ligand design suppressing the phenolic interaction by esterification or etherification has afforded a significant increase in the number of known crystal structures of homoleptic metal complexes of curcuminoids revealing more favorable crystallinity. The crystal structures of the present new copper complexes show four-fold coordination with a square planar geometry. Two polymorphs were found for DiBncOC-Cu when crystallized from DMF. The characterization of these new complexes was carried out using infrared radiation (IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and single crystal X-ray diffraction (SCXRD) and the antioxidant and cytotoxic activity of the obtained complexes was evaluated.

Dibutyltin(IV) Complexes Derived from L-DOPA: Synthesis, Molecular Docking, Cytotoxic and Antifungal Activity.

A series of organotin(IV) complexes was herein prepared and characterized. A one-pot synthetic strategy afforded reasonable to high yields, depending on the nature of the ligand. All new complexes were fully characterized by spectroscopic techniques, consisting of IR, MS and NMR (1H, 13C and 119Sn). The in vitro cytotoxicity tests demonstrated that the organotin complexes produced a greater inhibition, versus cisplatin (the positive control), of the growth of six human cancer cell lines: U-251 (glioblastoma), K-562 (chronic myelogenous leukemia), HCT-15 (colorectal), MCF-7 (breast), MDA-MB-231 (breast) and SKLU-1 (non-small cell lung). The potency of this cytotoxic activity depended on the nature of the substituent bonded to the aromatic ring. All complexes exhibited excellent IC50 values. The test compounds were also screened in vitro for their antifungal effect against Candida glabrata and Candida albicans, showing minimum inhibitory concentration (MIC) values lower than those obtained for fluconazole. A brine shrimp bioassay was performed to examine the toxic properties. Molecular docking studies demonstrated that the organotin(IV) complexes bind at the active site of topoisomerase I in a similar manner to topotecan, sharing affinity for certain amino acid side chains (Ile535, Arg364 and Asp533), as well as for similar DNA regions (DA113, DC112 and DT10).

Water-soluble porphyrin-PAMAM-conjugates of melphalan and their anticancer activity.

p-[bis(chloro-2-ethyl)amino]-L-phenylalanine (melphalan) is an approved anti-cancer agent with a broad spectrum of antitumor activity. However, it has some disadvantages, such as poor water-solubility followed by rapid elimination, which reduce the target specificity. To solve these problems, porphyrin- poly(amidoamine) or PAMAM-conjugates of melphalan were synthesized and characterized. The dendrimeric conjugates showed satisfactory water solubility. It was found that the size of the dendrimer played a crucial role in controlling the drug content and diameter of the melphalan-conjugates. The in vitro studies of cell cytotoxicity revealed that by employing the dendrimeric conjugation strategy and using the PAMAM dendritic arms as spacers, the conjugates had good anti-cancer activity and lower toxicity than free melphalan.

Mexican Propolis: A Source of Antioxidants and Anti-Inflammatory Compounds, and Isolation of a Novel Chalcone and ε-Caprolactone Derivative.

The propolis produced by bees are used in alternative medicine for treating inflammation, and infections, presumably due to its antioxidant properties. In this context, five propolis from México were investigated to determine their inhibitory lipid peroxidation properties. The ethyl acetate extract from a red propolis from Chiapas State (4-EAEP) was the most potent (IC50 = 1.42 ± 0.07 µg/mL) in the TBARS assay, and selected for further studies. This extract afforded two new compounds, epoxypinocembrin chalcone (6), and an ε-caprolactone derivative (10), as well as pinostrobin (1), izalpinin (2), cinnamic acid (3), pinocembrin (4), kaempherol (5), 3,3-dimethylallyl caffeate in mixture with isopent-3-enyl caffeate (7a + 7b), 3,4-dimethoxycinnamic acid (8), rhamnetin (9) and caffeic acid (11). The HPLC profile, anti-mycobacterial, and antioxidant properties of this extract was also determined. Most of the isolated compounds were also tested by inhibition of reactive oxygen species (ROS) in challenged mouse bone marrow-derived mast cells (BMMCs), and DPPH. Their anti-inflammatory activity was evaluated by TPA, and MPO (myeloperoxidase) activity by ear edema test in mice. The most potent compounds were 7a + 7b in the TBARS assay (IC50 = 0.49 ± 0.06 µM), and 2 which restored the ROS baseline (3.5 µM). Our results indicate that 4-EAEP has anti-oxidant, and anti-inflammatory properties due to its active compounds, suggesting it has anti-allergy and anti-asthma potential.

Structure, Absolute Configuration, and Antiproliferative Activity of Abietane and Icetexane Diterpenoids from Salvia ballotiflora.

From the aerial parts of Salvia ballotiflora, eleven diterpenoids were isolated; among them, four icetexanes and one abietane (1-5) are reported for the first time. Their structures were established by spectroscopic means, mainly ¹H- and 13C-NMR, including 1D and 2D homo- and hetero-nuclear experiments. Most of the isolated diterpenoids were tested for their antiproliferative, anti-inflammatory, and radical scavenging activities using the sulforhodamine B assay on six cancer cell lines, the TPA-induced ear edema test in mice, and the reduction of the DPPH assay, respectively. Some diterpenoids showed anti-proliferative activity, these being icetexanes 6 and 3, which were the most active with IC50 (µM) = 0.27 ± 0.08 and 1.40 ± 0.03, respectively, for U251 (human glioblastoma) and IC50 (µM) = 0.0.46 ± 0.05 and 0.82 ± 0.06 for SKLU-1 (human lung adenocarcinoma), when compared with adriamycin (IC50 (µM) = 0.08 ± 0.003 and 0.05 ± 0.003, as the positive control), respectively. Compounds 3 and 10 showed significant reduction of the induced ear edema of 37.4 ± 2.8 and 25.4 ± 3.0% (at 1.0 µmol/ear), respectively. Compound 4 was the sole active diterpenoid in the antioxidant assay (IC50 = 98. 4 ± 3.3), using α-tocopherol as the positive control (IC50 (µM) = 31.7 ± 1.04). The diterpenoid profile found is of chemotaxonomic relevance and reinforces the evolutionary link of S. ballotiflora with other members of the section Tomentellae.

Synthesis of Curcuminoids and Evaluation of Their Cytotoxic and Antioxidant Properties.

Curcumin (1) and ten derivatives (2-11) were synthesized and evaluated as cytotoxic and antioxidant agents. The results of primary screening by Sulforhodamine B assay against five human cancer cell lines (U-251 MG, glioblastoma; PC-3, human prostatic; HCT-15, human colorectal; K562, human chronic myelogenous leukemia; and SKLU-1, non-small cell lung cancer) allowed us to calculate the half maximal inhibitory concentration (IC50) values for the more active compounds against HCT-15 and K562 cell lines. Compounds 2 and 10 were the most active against both cell lines and were more active than curcumin itself. Thiobarbituric acid reactive substances (TBARS) assay showed that 7 has potent activity; even stronger than curcumin, α-tocopherol, and quercetin.

Evaluation of antioxidant and hepatoprotective effects of white cabbage essential oil.

CONTEXT: There have been no reports of the extraction of essential oil (EO) from white cabbage [Brassica oleracea L. var. capitata (L.) Alef. f. alba DC. (Brassicaceae)] (Bocfal) or its chemical composition, antioxidant activity, or hepatoprotective effects. OBJECTIVE: To extract Bocfal EO, to identify and quantify its chemical components, to assess their antioxidant capacity, and to evaluate the hepatoprotective properties of Bocfal EO. MATERIALS AND METHODS: Bocfal EO was obtained using hydrodistillation (200 mm Hg/58 °C). The chemical composition was analyzed using GC-MS and was quantified using GC-FID. The antioxidant activity of Bocfal EO and its main constituents was evaluated using TBARS in rat brain homogenates. A Bocfal EO hepatoprotective effect (192 mg/kg) on acute carbon tetrachloride (CT)-induced liver damage was determined in rats using biochemical markers and histological analysis. Diallyl disulphide (DADS) (1 mmol/kg) was used as a control for comparison. RESULTS: Bocfal EO contained organic polysulphides (OPSs), such as dimethyl trisulphide (DMTS) 65.43 ± 4.92% and dimethyl disulphide (DMDS) 19.29 ± 2.16% as major constituents. Bocfal EO and DMTS were found to be potent TBARS inhibitors with IC50 values of 0.51 and 3 mg/L, respectively. Bocfal EO demonstrated better hepatoprotective properties than did DADS (p < 0.05), although both slightly affected the hepatic parenchyma per se, as observed using histopathology. DISCUSSION AND CONCLUSION: The antioxidant properties of Bocfal EO and DMTS may be the mechanism of hepatoprotective action; the parenchymal disturbances by Bocfal EO or DADS alone may be related to the high doses used.