In vivo and In silico evidence of the protective properties of carvacrol against experimentally-induced gastric ulcer: Implication of antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

Gastric ulcer is a serious disease that affects millions of individuals worldwide. Alcohol consumption is a major contributor to the disease pathogenesis and ethanol-induced ulcer in rats closely recapitulates the clinical pathology of ulcer. In this study, rats were pretreated with carvacrol (CAR,50 and 100 mg/kg, orally) 1 h before absolute ethanol administration to induce gastric ulcer. CAR prevented ethanol-induced increases in gastric volume and acidity while restored mucin content. The gastro-protective activity of CAR, particularly the higher dose (100 mg/kg), was further supported by histopathological examination, as manifested by reduced gastric lesions. Interestingly, oxidative stress is linked to early stages of ulcer development and progression. In this study, ethanol administration upregulated the levels of ROS-producing enzymes, NADPH oxidase homologs 1 and 4 (Nox1 and Nox4) and lipid peroxides while depleting the antioxidant defense mechanisms, including GSH, Glutathione Peroxidase (GPX) and catalase. Interestingly, these alterations were significantly ameliorated by CAR pretreatment. Additionally, CAR possesses anti-inflammatory and anti-apoptotic activities. Pretreatment with CAR blunted ethanol-induced increases in inflammatory cytokines (NF-κB and TNF-α) and rectified the apoptosis regulator (Bax/Bcl2 ratio) in gastric tissue. Moreover, the docking simulation of CAR illustrated good fitting and interactions with GPX, Nox1 and TNF-α through the formation of hydrogen and hydrophobic (pi-H) bonds with conservative amino acids, thus, further supporting the anti-inflammatory and antioxidant effects underlying the gastroprotective effects of CAR. In conclusion, this study elucidates, using in silico and in vivo models, that the gastroprotective activity of CAR is attributed, at least in part, to its mucin-secretagogue, antioxidative, anti-inflammatory, and anti-apoptotic mechanisms.

Complete green synthesis of silver-nanoparticles applying seed-borne Penicillium duclauxii.

Seed-borne fungus Penicillium duclauxii was examined in this study to investigate its capability of synthesizing silver nanoparticles (Ag-NPs). In vitro experiments were conducted using corn-grain contaminating fungal isolate. Ag-NPs detection and characterization were assayed by the aid of spectroscopic techniques. Spectroscopy (energy dispersive), X-ray diffraction, transmission electron-microscope and optical absorption dimensions were employed. Ag-NPs with biosynthesized were used to test invitro against Bipolaris sorghicola; the cause of target leaf spot disease on sorghum plants. The myco-synthesis of Ag NPs using Penicillium duclauxii was proved in this study. Moreover, Bipolaris sorghicola was successfully inhibited by such Ag NPs in vitro.

Arctium lappa Root Extract Prevents Lead-Induced Liver Injury by Attenuating Oxidative Stress and Inflammation, and Activating Akt/GSK-3ß Signaling.

Arctium lappa L (A. lappa) is a popular medicinal plant with promising hepatoprotective activity. This study investigated the protective effect of A. lappa root extract (ALRE) on lead (Pb) hepatotoxicity, pointing to its ability to modulate oxidative stress, inflammation, and protein kinase B/Akt/glycogen synthase kinase (GSK)-3ß signaling. Rats received 50 mg/kg lead acetate (Pb(Ac)2) and 200 mg/kg ALRE or vitamin C (Vit. C) for 7 days, and blood and liver samples were collected. Pb(Ac)2 provoked hepatotoxicity manifested by elevated serum transaminases and lactate dehydrogenase, and decreased total protein. Histopathological alterations, including distorted lobular hepatic architecture, microsteatotic changes, congestion, and massive necrosis were observed in Pb(II)-induced rats. ALRE ameliorated liver function and prevented all histological alterations. Pb(II) increased hepatic lipid peroxidation (LPO), nitric oxide (NO), caspase-3, and DNA fragmentation, and serum C-reactive protein, tumor necrosis factor-α, and interleukin-1ß. Cellular antioxidants, and Akt and GSK-3ß phosphorylation levels were decreased in the liver of Pb(II)-induced rats. ALRE ameliorated LPO, NO, caspase-3, DNA fragmentation and inflammatory mediators, and boosted antioxidant defenses in Pb(II)-induced rats. In addition, ALRE activated Akt and inhibited GSK-3ß in the liver of Pb(II)-induced rats. In conclusion, ALRE inhibits liver injury in Pb(II)-intoxicated rats by attenuating oxidative injury and inflammation, and activation of Akt/GSK-3ß signaling pathway.

The implication of the crosstalk of Nrf2 with NOXs, and HMGB1 in ethanol-induced gastric ulcer: Potential protective effect is afforded by Raspberry Ketone.

Ethanol consumption is one of the common causative agents implicated in gastric ulcer development. Oxidative stress plays a major role in the induction and development of gastric ulceration. NADPH oxidases (NOXs) and Nuclear factor erythroid 2-related factor 2 (Nrf2) are key players in ethanol-induced ulcers. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. However, the role of HMGB1 in ethanol-induced gastric ulcer is not yet elucidated. Raspberry Ketone (RK) is a natural phenolic compound with antioxidant and anti-inflammatory properties. In the present study, absolute ethanol (7.5 ml/kg) was used to induce gastric ulceration in rats. Raspberry Ketone (RK) (50 mg/kg) was given orally one hour before the administration of absolute ethanol. Interestingly, ethanol-induced gastric ulcer was associated with Nrf2 downregulation, which was correlated with NOX-1, 2 NOX-4, and HMGB1 upregulation, and was significantly reversed by RK pre-treatment. RK pre-treatment provided 80% gastroprotection. Gastroprotective properties of RK were mediated via antioxidant, anti-inflammatory (suppression of NF-kB and tumor necrosis factor-α), and antiapoptotic activities (reduction of Bax/Bcl2 ratio). Gastroprotective properties of RK were confirmed by histopathological examination. In conclusion, this study is the first to provide evidence to the role of HMGB1 in ethanol-induced gastric ulcer, and the crosstalk of Nrf2, NOXs and HMGB1. It also demonstrates that RK represents a promising gastroprotective activity comparable to omeprazole.

Role of N-Acetylcysteine and Coenzyme Q10 in the Amelioration of Myocardial Energy Expenditure and Oxidative Stress, Induced by Carbon Tetrachloride Intoxication in Rats.

This study is designed to evaluate the potential impact of N-acetyl cysteine (NAC) and coenzyme Q10 (CoQ10) each alone or in combination against carbon tetrachloride (CCl4)-induced cardiac damage in rats. Animals were treated with CCl4 in single intraperitoneal dose of 1 mL/Kg body weight; CCl4-intoxicated animals were pretreated with 20 mg/kg/d NAC or pretreated with 200 mg/kg/d CoQ10 or NAC and CoQ10 with the same previously mentioned doses. Carbon tetrachloride-intoxicated rats showed a significant elevation in nitric oxide and lipid peroxides and downregulation in reduced glutathione level and calcium adenosine triphosphatase. Cardiac glycolytic enzymes levels such as lactate dehydrogenase, phosphofructokinase, and hexokinase were declined coupled with a reduction in glucose content after CCl4 treatment. Moreover, myocardial hydroxyproline level was significantly increased after CCl4-treatment indicating accumulation of interstitial collagen. N-acetyl cysteine and/or CoQ10 effectively alleviated the disturbances in myocardial oxidative stress and antioxidant markers. These antioxidants effectively upregulated the reduction in cardiac energetic biomarkers due to CCl4 treatment. N-acetyl cysteine and/or CoQ10 significantly decreased hydroxyproline level compared to that of CCl4-treated rats. The current data showed that the aforementioned antioxidants have a remarkable cardioprotective effect, suggesting that they may be useful as prophylactic agents against the detrimental effects of cardiotoxins.

Role of Some Natural Antioxidants in the Modulation of Some Proteins Expressions against Sodium Fluoride-Induced Renal Injury.

BACKGROUND: The aim of the present work is to find the effects of N-acetylcysteine (NAC) and/or thymoquinone (THQ) in the protection against acute renal injury induced by sodium fluoride (NaF). METHOD: Rats were distributed into five groups: G1 was normal (control), G2 was intoxicated with 10mg/kg NaF i.p., G3 was treated with 10mg THQ /kg, G4 was treated with 20mg NAC /kg, and G5 was treated with a combination of THQ and NAC. The previous treatments were given daily along with NaF for four weeks orally. RESULT: Rats intoxicated with NaF showed a significant increase in serum urea, creatinine, uric acid, renal lipid peroxidation, nitric oxide, and TNF-α levels, whereas the activity of superoxide dismutase (SOD) and glutathione (GSH) level was reduced. The expressions of Toll-like receptor-4 (TLR4), Lipocalin, vascular adhesion molecule-1(VCAM-1), and BAX proteins were upregulated, whereas Bcl-2 and NF-E2-related factor 2 (Nrf2) proteins expressions were downregulated. DNA fragmentation was also amplified. Histological analysis revealed that NaF caused a destructive renal cortex in the form of the glomerular corpuscle, the obliterated proximal and distal convoluted tubules, vacuolization in tubular cells focal necrosis, and cell infiltration. THQ and NAC supplementation counteracted NaF-induced nephrotoxicity as reflected by the increase in renal GSH and SOD. THQ and NAC ameliorated all the altered proteins expressions, improved renal architecture, and declined DNA fragmentation. CONCLUSION: The role of oxidative stress in the enhancement of NaF toxicity suggested the renoprotective effects of NAC and THQ against the toxicity of fluoride via multiple mechanisms.

Role of Different Natural Antioxidants in the Modulation of mRNA-expression of Apoptotic Molecules in the Livers of Carbon Tetrachloride-Intoxicated Rats.

Overexpression of nuclear factor (NF-κB) or activation of Smad3 by transforming growth factor ß (TGF-ß1) induced by oncogenes results in overexpression of fibrotic processes and hence cell death. The objective of this study is to examine whether Silymarin (Sil) alone or in combination with Vitamin E (Vit E) and/or Curcumin (Cur) plays a modulatory role against the overexpression of NF-κB, and TGF-ß that induced in response to carbon tetrachloride (CCl4) administration. The present work revealed that CCl4 induced elevation of in serum alanine aminotransferase (ALT), Apoptosis regulator (Bax), Smad3, TGF-ß, and NF-kB hepatic mRNA expression (using Real-time PCR), administration of Sil alone downregulated these expressions. Treatment with Vit E acid and/ or Cur along with Sil produced best results in this concern. B-cell lymphoma 2 (Bcl-2) expressions were downregulated by CCl4; whereas concurrent treatment of Vit E and/or Cur along with Sil increased its expression. On conclusion, the use of Vit E and/or Cur could potentiate the antiapoptotic action of Sil.

New mechanism in the modulation of carbon tetrachloride hepatotoxicity in rats using different natural antioxidants.

Transforming growth factor-ß (TGF-ß1) enhances the expression of apoptosis induced by certain cytokines and oncogenes. Activation of small mother against decapentaplegic (Smads) by TGF-ß results in fibrotic, apoptotic processes. PI-3/AKT focal adhesion kinase-phosphatidylinositol3-kinase (AKT), the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription-3 (STAT3) pathways are influence in COX-2 and VEGF-stimulating pathways. NF-E2-related factor-2 (Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense genes expression in the liver. The objective of this study is to examine whether silymarin alone or in combination with vitamin E and/or curcumin plays a modulatory role against MAPK, STAT3, AKT, Smad-2 and TGF-ß protein expressions that produced apoptotic damage in rat's liver by the administration of carbon tetrachloride (CCl4). The results of the present work revealed that CCl4-induced an elevation of serum alanine aminotransferase (ALT) with concomitant increase in MAPK, STAT3, AKT, Smad-2 and TGF-ß hepatic protein expression, administration of silymarin alone down regulates these expressions. Treatment with vitamin E and/or curcumin along with silymarin produced best results in this concern. On the other hand, Nrf2 protein expression was down regulated by CCl4 whereas concurrent treatment with vitamin E and/or curcumin along with silymarin increased this expression. It was concluded that CCl4-induced protein expression of apoptotic and fibenorgenic factors. Whereas administration of silymarin alone or in combination with vitamin E and/or curcumin plays a modulatory role against the previous aforementioned apoptotic factors expressions. The use of vitamin E and/or curcumin potentiates the anti-apoptotic action of silymarin. So this combination can be used as hepatoprotective agent against other hepatotoxic substances.

Effect of evening primrose oil and ω-3 polyunsaturated fatty acids on the cardiovascular risk of celecoxib in rats.

Experimental data raised the specter of increased cardiovascular risk with selective cyclooxygenase-2 inhibitors. The study aimed to investigate the cardiovascular risk caused by celecoxib by studying its effect on blood pressure (BP) and thrombogenesis in rats. We tested the possible protective effects of evening primrose oil (EPO) or ω-3 polyunsaturated fatty acids (n-3 PUFAs). Male Wistar rats were assigned to the following groups: vehicle, celecoxib, celecoxib/n-3 PUFAs, celecoxib/EPO, n-3 PUFAs, and EPO. The rats were treated with celecoxib (20 mg·kg(-1)·d(-1)) by gastric gavage for 6 weeks. The mean BP was recorded, and blood samples were collected for testing prothrombin time and activated partial thromboplastin time. Platelet aggregation assay and collagen-induced platelet consumption test were used as models of thrombogenesis. Celecoxib increased the BP without affecting coagulation parameters and accelerated thrombogenesis by increasing platelet aggregation and collagen-induced thrombocytopenia. EPO and n-3 PUFAs decreased the celecoxib-induced elevation in BP. Although EPO significantly decreased platelet aggregation and collagen-induced thrombocytopenia, n-3 PUFAs did not. Celecoxib elevated BP and increased the risk of thrombogenesis in rats. A combination of celecoxib and the selected natural supplements is suggested as a novel approach to minimize cardiovascular risk caused by celecoxib.