Synthesis and biological research of new imidazolone-sulphonamide-pyrimidine hybrids as potential EGFR-TK inhibitors and apoptosis-inducing agents.

Development of new effective EGFR-targeted antitumor agents is needed because of their clinical significance. A new series of imidazolone-sulphonamide-pyrimidine hybrids was designed and synthesized as modified analogs of some reported EGFR inhibitors. The cytotoxic activity of all the synthesized hybrids was investigated against the breast MCF-7 cancerous cell line using doxorubicin (Dox) as a positive control. 4-(Furan-2-ylmethylene)imidazolone-sulphonamide-pyrimidine 6b had the best potent activity against MCF-7 cells with IC50 result of 1.05 µM, which was better than Dox (IC50 = 1.91 µM). In addition, mechanistic studies revealed the ability of compounds 5g, 5h and 6b to inhibit EGFR kinase. Cell cycle analysis revealed that compound 6b can halt MCF-7 cells at the G1 phase with a concomitant decrease in cellular percentage at the S and G2/M phases. This compound produced a noticeable rise in the proportion of apoptotic cells with regard to the untreated control. Furthermore, the effects of hybrid 6b on the expression levels of pro-apoptotic Bax and pro-survival Bcl2 were assessed. The results showed that this compound upregulated the level of Bax expression as well as declined the expression value of Bcl-2 with regard to the untreated control.

Novel Acrylate-Based Derivatives: Design, Synthesis, Antiproliferative Screening, and Docking Study as Potential Combretastatin Analogues.

A variety of 3-(4-chlorophenyl) acrylic acids 4a,b and 3-(4-chlorophenyl)acrylate esters 5a-i were synthesized and structurally proven by spectroscopic studies such as IR, 1H NMR, and 13C NMR as well as mass spectrometry. All substances were investigated for their antiproliferative efficacy against the MDA-MB-231 cell line. Among these, acrylic acid compound 4b demonstrated the most potent cytotoxic effect with an IC50 value of 3.24 ± 0.13 µM, as compared to CA-4 (IC50 = 1.27 ± 09 µM). Additionally, acrylic acid molecule 4b displayed an inhibitory effect against ß-tubulin polymerization with a percentage inhibition of 80.07%. Furthermore, compound 4b was found to produce considerable cell cycle arrest at the G2/M stage and cellular death, as demonstrated by FACS analysis. In addition, the in vivo antitumor screening of the sodium salt of acrylic acid 4b was carried out, and the results have shown that the tested molecule showed a significant decrease in viable EAC count and EAC volume, accompanied by a considerable increase in the life span prolongation, if compared to the positive control group. Furthermore, molecular modeling studies were performed to understand how the highly efficient chemicals 4b and 5e interact with the colchicine-binding region on tubulin. This work aims to shed light on the reasons behind their exceptional cytotoxicity and their better capacity to inhibit tubulin in comparison to CA-4.

Bioactivity of hamamelitannin, flavokawain A, and triacetyl resveratrol as natural compounds: Molecular docking study, anticolon cancer, and anti-Alzheimer potentials.

In this study, we worked on anticolon cancer effects and anti-Alzheimer's disease with molecular docking studies. Hamamelitannin, flavokawain A, and triacetyl resveratrol compounds showed good inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. The inhibition effects of flavokawain A, hamamelitannin, and triacetyl resveratrol on AChE and BuChE enzymes were determined spectrophotometrically conforming to Ellman. IC50 values of these enzymes were ranging between 0.95 ± 0.12 and 93.27 ± 8.14 nM for AChE and 5.71 ± 0.77 and 52.10 ± 8.41 nM for BuChE. The inhibitory activities of some chemical compounds such as flavokawain A, hamamelitannin, and triacetyl resveratrol were assessed by performing the molecular docking study in the presence of AChE and BuChE. Also, the features of the ligand-enzyme complex had value of -7.722 kcal/mol for flavokawain A against AChE and -5.530 kcal/mol against BuChE. The molecular docking calculations indicated the probable interactions and their characteristics at an atomic level. Due to the outcomes gained from docking, the affinity of the chemical compounds to the enzymes was considerable. In vitro cell viabilities of flavokawain A, hamamelitannin, and triacetyl resveratrol with various concentrations on SW620, DLD-1, HT29, HCT8, and HCT116 were investigated by MTT assay with Doxorubicin as the control compound.

Effect of Vegetable Waste on Growth Performance and Hematology of Broiler Chicks.

Vegetable waste (spinach, potato, and cauliflower) is a rich and natural source of nutrients, potentially good for supplying minerals, essential amino acids, and antioxidants to the birds. Relatively, its cost very low, easily to accessible, easily process & pose little risk of illness. The aim of present study was to evaluate the effect of vegetable waste (VW) as feed supplement on growth performance and hematology of broiler chicks. For this purpose, a total of 200 (4 days old) vaccinated chicks were acquired from a commercial hatchery Multan which was acclimated for three weeks (21 days) on basal starter feed after that 25-day-old chicks with uniform body weight were allocated according to a CRD (completely randomized design) into four dietary treatments with three replicates of each contained 15 chicks in 12 pens. In dietary treatments, chicks were feed with basal feed (BF) and supplemented feed with vegetable waste (VW) of spinach, potato, and cauliflower. For this purpose, the dietary treatments included control treatment (T 1) (100% BF+0% VW) and other dietary treatments (T 2) (75% BF+25% VW), (T 3) (50% BF+50% VW), and (T 4) (25% BF+75% VW). The body weight, feed intake, food conversion ratio (FCR), and mortality were checked on weekly and daily basis. For hematology analysis, after the 1st experimental week (25-day-old chicks) and the last 5th experimental week (56-day-old chicks), the samples of blood were gathered from the wing's veins of two birds from each treatment in random way. At the end of five weeks (35 days), birds with uniform average body weight were selected per treatment with three replicates (2 bird/replicate) and then were manually slaughtered according to the Halal method to analyze the weight of internal body organs of broilers by physical and statistical analysis (ANOVA). There was no significant effect (P > 0.05) on feed intake and FCR among all the dietary treatments. But in average, body weight and BWG were higher in treatment (T 2) (P < 0.01) than all other dietary treatments (T 3) and (T 4) and control treatment (T 1). The blood constituents in this study showed that broilers in control treatment (T 1) and other dietary treatments (T 2), (T 3), and (T 4) fed on different doses were significantly (P < 0.01) different from each other. The week 5 (W 5) shows higher values of blood constituents (P < 0.01) than week 1 (W 1). The carcass yield of the chicks fed on different doses showed that they were significantly different (P < 0.01) among the dietary treatments. The VW inclusion 0%, 25%, 50%, and 75% had positive effect on blood constituents and carcass yield of the broiler chicks; they were significantly (P < 0.01) different among the treatments.

Optimization of Supercritical Carbon Dioxide Extraction of Saussurea costus Oil and Its Antimicrobial, Antioxidant, and Anticancer Activities.

Saussurea costus is a medicinal plant with different bioactive compounds that have an essential role in biomedicine applications, especially in Arab nations. However, traditional extraction methods for oils can lead to the loss of some volatile and non-volatile oils. Therefore, this study aimed to optimize the supercritical fluid extraction (SFE) of oils from S. costus at pressures (10, 20, and 48 MPa). The results were investigated by GC/MS analysis. MTT, DPPH, and agar diffusion methods assessed the extracted oils' anticancer, antioxidant, and antimicrobial action. GC/MS results showed that elevated pressure from 10 to 20 and 48 MPa led to the loss of some valuable compounds. In addition, the best IC50 values were recorded at 10 MPa on HCT, MCF-7, and HepG-2 cells at about 0.44, 0.46, and 0.74 µg/mL, respectively. In contrast, at 20 MPa, the IC50 values were about 2.33, 6.59, and 19.0 µg/mL, respectively, on HCT, MCF-7, and HepG-2 cells, followed by 48 MPa, about 36.02, 59.5, and 96.9 µg/mL. The oil extract at a pressure of 10 MPa contained much more of á-elemene, dihydro-à-ionone, patchoulene, á-maaliene, à-selinene, (-)-spathulenol, cedran-diol, 8S,13, elemol, eremanthin, á-guaiene, eudesmol, ç-gurjunenepoxide-(2), iso-velleral, and propanedioic acid and had a higher antioxidant activity (IC50 14.4 µg/mL) more than the oil extract at 20 and 48 MPa. In addition, the inhibitory activity of all extracts was higher than gentamicin against all tested bacteria. One of the more significant findings from this study is low pressure in SFE enhancement, the extraction of oils from S. costus, for the first time. As a result, the SFE is regarded as a good extraction technique since it is both quick and ecologically friendly. Furthermore, SFE at 10 MPa increased the production and quality of oils, with high antioxidant activity and a positive effect on cancer cells and pathogens.

Ameliorative Effect of Pomegranate Peel Extract (PPE) on Hepatotoxicity Prompted by Iron Oxide Nanoparticles (Fe2O3-NPs) in Mice.

An evaluation of the ameliorative effect of pomegranate peel extract (PPE) in counteracting the toxicity of iron oxide nanoparticles (Fe2O3-NPs) that cause hepatic tissue damage is focused on herein. Forty male albino mice were haphazardly grouped into four groups as follows: the first control group was orally gavage daily with physiological saline; the second group received 100 mg/kg of PPE by the oral route day after day; the third group received 30 mg/kg Fe2O3-NPs orally; and the fourth group received both PPE and Fe2O3-NPs by the oral route, the same as the second and third sets. Later, after the completion of the experiment, we collected the liver, blood, and bone marrow of bone specimens that were obtained for further laboratory tests. For instance, exposure to Fe2O3-NPs significantly altered serum antioxidant biomarkers by decreasing the levels of total antioxidant capacity (TAC), catalase (CAT), and glutathione s-transferase (GST). Additionally, it caused changes in the morphology of hepatocytes, hepatic sinusoids, and inflammatory Kupffer cells. Furthermore, they significantly elevated the number of chromosomal aberrations including gaps, breaks, deletions, fragments, polyploidies, and ring chromosomes. Moreover, they caused a significant overexpression of TIMP-1, TNF-α, and BAX mRNA levels. Finally, the use of PPE alleviates the toxicity of Fe2O3-NPs that were induced in the hepatic tissues of mice. It is concluded that PPE extract has mitigative roles against the damage induced by Fe2O3-NPs, as it serves as an antioxidant and hepatoprotective agent. The use of PPE as a modulator of Fe2O3-NPs' hepatotoxicity could be considered as a pioneering method in the use of phytochemicals against the toxicity of nanoparticles.

Scaffold Repurposing Reveals New Nanomolar Phosphodiesterase Type 5 (PDE5) Inhibitors Based on Pyridopyrazinone Scaffold: Investigation of In Vitro and In Silico Properties.

Inhibition of PDE5 results in elevation of cGMP leading to vascular relaxation and reduction in the systemic blood pressure. Therefore, PDE5 inhibitors are used as antihypertensive and antianginal agents in addition to their major use as male erectile dysfunction treatments. Previously, we developed a novel series of 34 pyridopyrazinone derivatives as anticancer agents (series A-H). Herein, a multi-step in silico approach was preliminary conducted to evaluate the predicted PDE5 inhibitory activity, followed by an in vitro biological evaluation over the enzymatic level and a detailed SAR study. The designed 2D-QSAR model which was carried out to predict the IC50 of the tested compounds revealed series B, D, E and G with nanomolar range of IC50 values (6.00-81.56 nM). A further docking simulation model was performed to investigate the binding modes within the active site of PDE5. Interestingly, most of the tested compounds showed almost the same binding modes of that of reported PDE5 inhibitors. To validate the in silico results, an in vitro enzymatic assay over PDE5 enzyme was performed for a number of the promising candidates with different substitutions. Both series E and G exhibited a potent inhibitory activity (IC50 = 18.13-41.41 nM). Compound 11b (series G, oxadiazole-based derivatives with terminal 4-NO2 substituted phenyl ring and rigid linker) was the most potent analogue with IC50 value of 18.13 nM. Structure-activity relationship (SAR) data attained for various substitutions were rationalized. Furthermore, a molecular dynamic simulation gave insights into the inhibitory activity of the most active compound (11b). Accordingly, this report presents a successful scaffold repurposing approach that reveals compound 11b as a highly potent nanomolar PDE5 inhibitor worthy of further investigation.

Synthesis and Biological Activity Screening of Newly Synthesized Trimethoxyphenyl-Based Analogues as Potential Anticancer Agents.

A group of novel trimethoxyphenyl (TMP)-based analogues were synthesized by varying the azalactone ring of 2-(3,4-dimethoxyphenyl)-4-(3,4,5-trimethoxybenzylidene)oxazolone 1 and characterized using NMR spectral data as well as elemental microanalyses. All synthesized compounds were screened for their cytotoxic activity utilizing the hepatocellular carcinoma (HepG2) cell line. Compounds 9, 10 and 11 exhibited good cytotoxic potency with IC50 values ranging from 1.38 to 3.21 µM compared to podophyllotoxin (podo) as a reference compound. In addition, compounds 9, 10 and 11 exhibited potent inhibition of ß-tubulin polymerization. DNA flow cytometry analysis of compound 9 shows cell cycle disturbance at the G2/M phase and a significant increase in Annexin-V-positive cells compared with the untreated control. Compound 9 was further studied regarding its apoptotic potential in HepG2 cells; it decreased the level of MMP and Bcl-2 as well as boosted the level of p53 and Bax compared with the control HepG2 cells.

Phenolic Characterization Using cLC-DAD Analysis and Evaluation of In Vitro and In Vivo Pharmacological Activities of Ruta tuberculata Forssk.

The perennial aromatic plant Ruta tuberculata Forssk (Rutaceae) has been traditionally used by Mediterranean peoples as folk medicine against several types of disease to treat diverse illness. The objective of this work is to evaluate the in vitro and in vivo pharmacological activities of the aqueous (RAE) and methanolic (MeOH) 80% (RME) extracts of Algerian R. tuberculata aerial parts. Antioxidant potential, neuro-protective and anti-arthritic activities were investigated in vitro using six antioxidant approaches and by determining acetyl-cholinesterase and bovine albumin denaturation inhibitory capacities, respectively. Furthermore, in vivo anti-ulcer and anti-inflammatory activities were evaluated on EtOH-induced gastric mucosal damage and carrageenan-induced paw edema models in mice. Moreover, bio-compounds' contents were also quantified using spectrophotometric and cLC-DAD methods. Both in vivo and in vitro investigations showed remarkable antioxidant activity of Ruta tuberculata Forssk, while methanolic extract (RME) of Ruta tuberculata Forssk exhibited more significant neuro-protective and anti-inflammatory effects. However, the antiulcer activity was more pronounced with RAE of R. tuberculata, which suggests that this plant can be considered as a natural resource of potent bioactive compounds that may act as antioxidant and anti-inflammatory agents, which underlines the importance of incorporating them in therapies in order to treat various diseases linked to oxidative stress, and they may also provide crucial data for the development of new anticholinesterase drugs to improve neurodegenerative diseases, such as Alzheimer's.

Salidroside inhibits insulin resistance and hepatic steatosis by downregulating miR-21 and subsequent activation of AMPK and upregulation of PPARα in the liver and muscles of high fat diet-fed rats.

This study evaluated if salidroside (SAL) alleviates high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) by downregulating miR-21. Rats (n = 8/group) were treated for 12 weeks as normal diet (control/ND), ND + agmoir negative control (NC) (150 µg/kg), ND + SAL (300 mg/kg), HFD, HFD + SAL, HFD + compound C (an AMPK inhibitor) (200 ng/kg), HFD + SAL + NXT629 (a PPAR-α antagonist) (30 mg/kg), and HFD + SAL + miR-21 agomir (150 µg/kg). SAL improved glucose and insulin tolerance and preserved livers in HFD-fed rats. In ND and HFD-fed rats, SAL reduced levels of serum and hepatic lipids and the hepatic expression of SREBP1, SREBP2, fatty acid (FA) synthase, and HMGCOAR. It also activated hepatic Nrf2 and increased hepatic/muscular activity of AMPK and levels of PPARα. All effects afforded by SAL were prevented by CC, NXT629, and miR-21 agmoir. In conclusion, activation of AMPK and upregulation of PPARα mediate the anti-steatotic effect of SAL.

Secondary Metabolites of Saussurea costus Leaf Extract Induce Apoptosis in Breast, Liver, and Colon Cancer Cells by Caspase-3-Dependent Intrinsic Pathway.

BACKGROUND: Apoptosis, a major form of programmed cell death, plays a vital role in regulating tissue development and maintenance of homeostasis in eukaryotes. Apoptosis can occur via a death receptor-dependent extrinsic or a mitochondrial-dependent intrinsic pathway and can be induced by various chemotherapeutic agents. In this study, the anticancer activity of Saussurea costus and its mode of intervention in human cancer cells of breast, colon, and liver were investigated. RESULTS: In this study, the bioactives of S. costus leaves were extensively extracted in five solvents of different polarity. The cytotoxicity and anticancer effect of the extracted secondary metabolites were investigated against breast (MCF-7), liver (HepG2), and colon (HCT116) cancer cell lines using a Sulphorhodamine B (SRB) assay. Secondary metabolites extracted using hexane, methanol, ethyl acetate, and chloroform had the highest cytotoxicity and thus the greatest anticancer effect on all the cancer cell lines tested (IC50; ranging from 0.25 to 2.5 µg/ml), while butanol was comparatively less active (IC50; ranging from 23.2 to 25.5 µg/ml). Further investigation using DNA flow cytometry and fluorescent microscopy revealed that the extract arrested the cells in the G1 phase of cell cycle and induced apoptosis. Furthermore, the elevated expression level of proapoptotic proteins and decreased expression level of antiapoptotic proteins confirmed that the intrinsic (mitochondrial) pathway was involved in mediating the apoptosis of cancer cells upon treatment with S. costus extract. These results altogether suggest that S. costus could be a potential anticancer agent. CONCLUSION: These results suggest that the S. costus extract is the potential source of the secondary metabolites that could be used as anticancer agent to treat diverse cancers of breast, colon, and liver.

The anti-tumourigenic effect of ellagic acid in SKOV-3 ovarian cancer cells entails activation of autophagy mediated by inhibiting Akt and activating AMPK.

This study investigated the effect of ellagic acid (EA) on SKOV-3 cell growth and invasiveness and tested if the underlying mechanism involves modulating autophagy. Cells were treated with EA in the presence or absence of chloroquine (CQ), an autophagy inhibitor, compound C (CC), an AMPK inhibitor, or an insulin-like growth factor-1 (IGF-1), a PI3K/Akt activator. EA, at an IC50 of 36.6 µmol/L, inhibited cell proliferation, migration, and invasion and induced cell apoptosis in SKOV-3 cells. These events were prevented by CQ. Also, EA increased levels of Beclin-1, ATG-5, LC3I/II, Bax, cleaved caspase-3/8 and reduced those of p62 and Bcl-2 in these cancer cells. Mechanistically, EA decreased levels of p-S6K1 (Thr389 ) and 4EBP-1 (Thr37/46 ), two downstream targets of mTORC1, and p-Akt (Thr308 ) but increased levels of AMPK (Thr172 ) and p-raptor (Ser792 ), a natural inhibitor of mTORC1. CC or IGF-1 alone partially prevented the effect of EA on cell survival, cell invasions, and levels of LDH, Beclin-1, and cleaved caspase-3. In conclusion, EA can inhibit SKOV-3 growth, migration, and invasion by activating cytotoxic autophagy mediated by inhibition of mTORC1 and Akt and activation of AMPK.

Biosynthesized silver nanoparticles and their genotoxicity.

The human-pathogenic bacteria have become highly resistant to conventional antibiotics; for this reason, a new biosynthesized nanomaterial might be a solution. The culture filtrate of two isolates of Fusarium oxysporum (14, 17) was used in the biosynthesis of nanosilver (AgNPs). The size of the nanoparticles produced by isolate F14 ranged from 19 to 30 nm, whereas the size of those formed via isolate F17 ranged between 16 and 25 nm. Moreover, the produced bio-nanosilver was tested against the human-pathogenic bacteria Proteus vulgaris, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumonia and the outcome results displayed great antibacterial efficacy in a different manner compared with the three different biogenic antibiotics. Collectively, the results depicted that the silver nanoparticles (AgNPs) showed a three and a half times greater activity than the used antibiotics. Differential display reverse transcription-polymerase chain reaction was used to study gene regulation in the treated E. coli (F14) compared with the nontreated ones. Different upregulated and downregulated genes were observed. The cytotoxicity of the produced AgNPs was examined on rats with an average body weight of 200 g each; these animals were grouped into three different groups. The obtained AgNPs showed very low toxicity on the treated rats in comparison to the control group. The physiological parameters, for example, alanine aminotransferase, aspartate transaminase, albumin, creatinine, and urea in the treated animals were changed within to a lower degree compared with those in the nontreated animals. The current study exhibited that AgNPs might be favorable antibacterial agents, especially against multidrug-resistant bacteria.

Hepatotoxic effect of subacute vincristine administration activates necrosis and intrinsic apoptosis in rats: protective roles of broccoli and Indian mustard.

This study investigated the hepatotoxic effect of long-term vincristine (VCR) administration in rats and to assess if an individual or combined therapy with Indian mustard and broccoli afforded protection. Signs of hepatotoxicity, including altered liver architecture and higher serum levels of ALT and AST, were seen in VCR-treated rats. Concomitantly, the impaired antioxidant potential and higher mRNA levels of IL-12 and IL-4, which are markers of apoptosis, were seen in rat livers. VCR treatment induced hepatocyte apoptosis, shown by the up-regulation of mRNA and protein levels of 53, increased protein levels of cleaved caspase-3 and Bax, and reduced levels of intracellular ATP and BCl-2mRNA and protein. Although individual administration of mustard or broccoli partially ameliorated all these responses, the combined therapy of both extracts resulted in the maximum improvement. Thus, the long-term administration of VCR is hepatotoxic and induces apoptosis; however, the combined therapy of both extracts mitigated these effects.

Biochemical and molecular studies on the possible influence of the Brassica oleracea and Beta vulgaris extracts to mitigate the effect of food preservatives and food chemical colorants on albino rats.

This study aimed to investigate the biochemical influence of broccoli and beet extracts on selected individual additives NaNO2 or sunset yellow treated rats, in addition to the gene expression of some antioxidant enzymes. Forty-two male rats were assigned to seven groups of six rats in each group. The control group was fed a diet without an additive for four weeks. Group (2) received NaNO2, groups (3) received NaNO2 co-administered with broccoli extract (4) NaNO2 co-administered with beet extracts, Group (5) received sunset yellow, Group (6) received sunset yellow co-administered with broccoli extract, and Group (7) received sunset yellow co-administered with beet extract, for four weeks. At the end of the experiment, blood, liver, kidney, and brain samples were taken for biochemical and/or molecular analysis. The mRNA expression of antioxidant enzymes was determined by reversing transcriptase-polymerase chain reaction (RT-PCR). The obtained results revealed that rats co-administered with beet or broccoli extracts had a significant decrease in serum levels of AST, ALT, ALP, urea, total lipids, and triglycerides, as well as a significant increase in reduced glutathione (GSH), glutathione peroxidase (GSH-px), and superoxide dismutase (SOD) enzyme activities, compared to the normal control group. Oral administration of NaNO2 or sunset yellow caused a significant increase in serum levels of AST, ALT, ALP, urea, total lipids, and triglycerides, as well as a significant decrease in GSH, GSH-px, and SOD compared to the positive group. In conclusion, this study showed that broccoli and beet extracts have a protective effect against NaNO2 or sunset yellow in rat treated groups.

Effects of water extracts of thyme (Thymus vulgaris) and ginger (Zingiber officinale Roscoe) on alcohol abuse.

INTRODUCTION: Alcohol abuse has many harmful effects on human body. This study aimed to investigate the role of water extracts of thyme (Thymus vulgaris) and ginger (Zingiber officinale Roscoe) as natural product extracts to detoxify the injuries of alcohol abuse on liver and brain of mice. MATERIALS AND METHODS: Alcohol at a dose of 1.25 ml/50 ml water was orally administered at the first day of treatment with continuously increase of 1.25 ml per day to the end of experiment (14 days, 0.1 ml/45 g /d). Mice also were orally administered with alcohol and water extracts of thyme and ginger in concentration of 500 mg /kg body weight for 2 weeks. RESULTS: The results showed very highly significant increase in nitric oxide and malondialdehyde level in liver and brain and a very highly significant decrease in the total antioxidant capacity and glutathione peroxidase activity in alcoholic group. In addition, the liver function enzymes such as L-gamma-glutamyl transpeptidase and butyryl cholinesterase activities showed very highly significant increase in alcoholic group. In contrast, the water extracts of thyme and ginger showed significant amelioration on these changes both in liver and brain tissues. CONCLUSION: The water extracts of thyme and ginger has detoxifying and antioxidant effects. Therefore, it is recommended to use them to avoid alcohol toxicity.