scholarly journals Hepatoprotective Effects of Garlic Extract against Carbon Tetrachloride (CCl4)-Induced Liver Injury via Modulation of Antioxidant, Anti-Inflammatory Activities and Hepatocyte Architecture

2020 ◽  
Vol 10 (18) ◽  
pp. 6200
Author(s):  
Saleh A. Almatroodi ◽  
Shehwaz Anwar ◽  
Ahmad Almatroudi ◽  
Amjad Ali Khan ◽  
Faris Alrumaihi ◽  
...  

The current study aims to explore the hepatoprotective mechanisms of garlic extract through in vivo and in vitro assays. The in vitro investigation of antioxidant and anti-inflammatory potential showed maximum 67.5% of free radical scavenging and 71.36% albumin denaturation inhibition by 600 μg/mL garlic extract. To explore the hepatoprotective activity by in vivo experiments, the animals were orally intoxicated with 150 μL of CCl4 (1:1 v/v in olive oil) and treated with garlic extract (75 mg/kg b.w.) 3 times/week, for eight successive weeks. The administration of garlic extract significantly ameliorated CCl4 induced increment in amounts of serum Alanine aminotransferase (ALT), Alkaline phosphatase (ALP) and Aspartate transaminaseas (106.7, 116.3, 136.4 U/L) as compared to disease control which showed increased level (140.5, 156.2, 187.6 U/L). Besides, significant reduction of Superoxide dismutase (SOD), Glutathione peroxidases (GPx), and Glutathione (GSH) (29.3, 48.4, and 25.9 U/mg protein) was noticed in CCl4 induced animals, respectively. Likewise, garlic extract treatment facilitated a significant increment in all tested antioxidant enzymes levels (41.6, 63.3, and 32.5 U/mg protein), respectively. Additionally, Tumor necrosis factor⍺ (TNF-⍺), C-reactive protein (CRP), Interleukin-1β (IL-1β), Interleukin 6 (IL-6) and ICAM-1 (Intercellular Adhesion Molecule 1) level (63.79, 580.2, 18.3, 63.74 and 148.4 pg/mL) were increased significantly in CCl4-induced group, while garlic extract treatment decreased these pro inflammatory marker levels (40.24, 460.4, 15.4, 45.14, and 125.3 pg/mL). The animals exposed to CCl4 showed various types of alterations like lymphocytes infiltration, edema and congestion, while the animals treated with garlic extract plus CCl4 showed amelioration of the hepatocytes architectures. Thus, our finding advocates that the consumption of garlic can be a potential therapeutic remedy in the inhibition of liver ailments.

2000 ◽  
Vol 279 (5) ◽  
pp. H2241-H2248 ◽  
Author(s):  
Hiroshi Saito ◽  
Cam Patterson ◽  
Zhaoyong Hu ◽  
Marschall S. Runge ◽  
Ulka Tipnis ◽  
...  

Interleukin (IL)-6 reportedly has negative inotropic and hypertrophic effects on the heart. Here, we describe endotoxin-induced IL-6 in the heart that has not previously been well characterized. An intraperitoneal injection of a bacterial lipopolysaccharide into C57BL/6 mice induced IL-6 mRNA in the heart more strongly than in any other tissue examined. Induction of mRNA for two proinflammatory cytokines, IL-1β and tumor necrosis factor (TNF)-α, occurred rapidly before the induction of IL-6 mRNA and protein. Although stimulation of isolated rat neonatal myocardial cells with IL-1β or TNF-α induced IL-6 mRNA in vitro, nonmyocardial heart cells produced higher levels of IL-6 mRNA upon stimulation with IL-1β. In situ hybridization and immunohistochemical analyses localized the IL-6 expression primarily in nonmyocardial cells in vivo. Endotoxin-induced expression of cardiac IL-1β, TNF-α, and intercellular adhesion molecule 1 was augmented in IL-6-deficient mice compared with control mice. Thus cardiac IL-6, expressed mainly by nonmyocardial cells via IL-1β action during endotoxemia, is likely to suppress expression of proinflammatory mediators and to regulate itself via a negative feedback mechanism.


2021 ◽  
Vol 18 ◽  
Author(s):  
Jagseer Singh ◽  
Pooja A Chawla ◽  
Rohit Bhatia ◽  
Shamsher Singh

: The present work reports synthesis and screening of fifteen 2,5-disubstituted-4-thiazolidinones with different substitutions of varied arylidene groups at imino. The structures of the compounds were confirmed by spectral characterization. The compounds were subjected to in vivo anti-inflammatory and in vitro antioxidant activities. The derivatives possessed remarkable activities quite close to standard drugs used. Unlike conventional non-selective NSAIDs, the synthesized compounds did not contain any acidic group, thereby ensuring a complete cure from ulcers. To further substantiate the claim for safer derivatives, the active compounds were docked against the cyclooxygenase (COX)-2 enzyme. It was found that 4-fluorophenylimino substituent at 2- position and 3-nitro moiety on a 5-benzylidene nucleus of the 4-thiazolidinone derivative fitted in the COX-2 binding pocket. The compounds exhibited remarkable activity in scavenging free radicals, as depicted by the DPPH assay method. The structure-activity relationship was also established in the present work with respect to the nature and position of the substituents. The active compounds were evaluated for drug-like nature under Lipinski’s rule of five, and the toxicity behaviour of active compounds was predicted using ADMETlab software. The compounds have the potential to target degenerative disorders associated with inflammation and the generation of free radicals.


2018 ◽  
Vol 13 (11) ◽  
pp. 1934578X1801301 ◽  
Author(s):  
Ying Zou ◽  
Min Zhang ◽  
Tingrui Zhang ◽  
Junwen Wu ◽  
Jun Wang ◽  
...  

The flavonoid fraction was obtained from Elsholtiza bodinieri Vaniot (EBV) by ethanol-reflux and liquid-liquid extraction. The total content of flavonoid was 179.55 mg/g, and the purity was 64.6%. Then cynaroside with the purity of 94% was isolated from the fraction by preparative HPLC and characterized by the combined usage of HPLC, ESI-MS, and NMR. The antioxidant activity of cynaroside was determined using 2 complementary methods, namely, 2,2- diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and reducing power assay. The anti-inflammatory effect of cynaroside was investigated based on in-vitro and in-vivo experiment. The results showed that cynaroside from EBV scavenged DPPH radical and reduced Fe3+ to Fe2+ effectively, inhibited NO and ROS production in LPS-stimulated RAW264.7 cells and attenuated the inflammation in the mouse model significantly ( p < 0.01), which showed it to be a nutraceutical product in the food industry.


2020 ◽  
Vol 21 (7) ◽  
pp. 2591
Author(s):  
Pablo Silva ◽  
Maria de Almeida ◽  
Jamire Silva ◽  
Sonaly Albino ◽  
Renan Espírito-Santo ◽  
...  

The compound (E)-2-cyano-3-(1H-indol-3-yl)-N-phenylacrylamide (ICMD-01) was designed and developed based on the structures of clinically relevant drugs indomethacin and paracetamol through the molecular hybridization strategy. This derivative was obtained by an amidation reaction between substituted anilines and ethyl 2-cyanoacetate followed by a Knoevenagel-type condensation reaction with indole aldehyde that resulted in both a viable synthesis and satisfactory yield. In order to assess the immunomodulatory and anti-inflammatory activity, in vitro assays were performed in J774 macrophages, and significant inhibitions (p < 0.05) of the production of nitrite and the production of cytokines (IL-1β and TNFα) in noncytotoxic concentrations were observed. The anti-inflammatory effect was also studied via CFA-induced paw edema in vivo tests and zymosan-induced peritonitis. In the paw edema assay, ICMD01 (50 mg kg−1) showed satisfactory activity, as did the group treated with dexamethasone, reducing edema in 2–6 h. In addition, there was no significant inhibition of PGE2, IL-1β or TNFα in vivo. Moreover, in the peritonitis assay that assesses leukocyte migration, ICMD-01 exhibited promising results. Therefore, these preliminary studies demonstrate this compound to be a strong candidate for an anti-inflammatory drug together with an improved gastrointestinal safety profile when compared to the conventional anti-inflammatory drugs.


Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2583-2593 ◽  
Author(s):  
SS Evans ◽  
DB Lee ◽  
T Han ◽  
TB Tomasi ◽  
RL Evans

Abstract Interferon (IFN)-alpha inhibits DNA synthesis stimulated by low molecular weight B-cell growth factor (BCGF) in hairy cells in vitro, suggesting that the therapeutic efficacy of IFN-alpha in hairy cell leukemia (HCL) involves growth inhibition of malignant B cells. Evidence that the 16-Kd cell surface protein Leu-13 mediates an antiproliferative signal in T lymphocytes and is IFN-inducible in endothelial cells prompted us to examine the expression and functional role of this molecule in leukemic B cells. Leu-13 density, determined by flow cytometry, was upregulated in vitro and in vivo by IFN-alpha on malignant B cells from patients with HCL, chronic lymphocytic leukemia, and prolymphocytic leukemia. Monoclonal anti-Leu-13 triggered homotypic aggregation of leukemic B cells via an adhesion pathway that was not inhibited by antibodies to leukocyte function associated antigen-1 (LFA- 1) or intercellular adhesion molecule-1 (ICAM-1). Moreover, anti-Leu-13 potentiated the inhibitory effects of IFN-alpha on BCGF-stimulated DNA synthesis, assessed by [3H]-thymidine and [3H]-deoxyadenosine incorporation into DNA. These results indicate that Leu-13 is part of a novel IFN-inducible signaling pathway which may modify the growth and adhesive properties of leukemic B cells under physiologic or therapeutic conditions.


2019 ◽  
Vol 20 (18) ◽  
pp. 4512 ◽  
Author(s):  
Alberto Jorge Oliveira Lopes ◽  
Cleydlenne Costa Vasconcelos ◽  
Francisco Assis Nascimento Pereira ◽  
Rosa Helena Moraes Silva ◽  
Pedro Felipe dos Santos Queiroz ◽  
...  

The stingless bee, Melipona fasciculata Smith (Apidae, Meliponini), is a native species from Brazil. Their products have high biotechnological potential, however there are no studies about the biological activities of pollen collected by M. fasciculata. In this context, the present study investigated the chemical composition, anti-oxidant, anti-inflammatory, and analgesic activities of hydroethanolic pollen extracts collected by M. fasciculata in three cities in Maranhão State, Brazil. We verified the antioxidant activity of the extracts and inhibitory activity against the cyclooxygenase enzyme using in vitro assays and in allowed to select the extract with higher efficiency to be used on in vivo assays. In these trials, the selected extract showed high anti-inflammatory activity as well as nociceptive effects at central and peripheral level, suggesting that this extract acts on inhibition of histamine release and decreased synthesis of prostaglandins and the in-silico study suggested that polyphenols and acids fatty acids in the extract may be associated with these activities. The results of the present study report the high biological potential of pollen extract and we conclude that the pollen collected by M. fasciculata can be considered as the object of research for new pharmacological alternatives.


Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4803-4809 ◽  
Author(s):  
May Ho ◽  
Tineke Schollaardt ◽  
Xiaofei Niu ◽  
Sornchai Looareesuwan ◽  
Kamala D. Patel ◽  
...  

Abstract Plasmodium falciparum-infected erythrocytes (IRBC) roll on the adhesion molecule P-selectin in vitro under flow conditions that approximate the shear stress in capillary and postcapillary venules in which cytoadherence occurs in vivo. The pathological significance of this adhesive interaction is currently unknown. In this study, we further investigated the molecular interactions between IRBC and P-selectin by using a laminar flow system that allowed for the direct visualization of IRBC-substratum interactions. The results showed that the IRBC–P-selectin interaction was Ca2+-dependent and involved the lectin domain of P-selectin and a sialic acid residue on IRBC. The sialylated P-selectin ligand was trypsin-sensitive, which suggests that it could be part of the parasite antigen PfEMP1 that interacts with CD36 and intercellular adhesion molecule-1 (ICAM-1), but different from a trypsin-resistant IRBC ligand that adheres selectively to chondroitin sulfate A. Studies on the rolling and adhesion of IRBC on activated platelets that express both CD36 and P-selectin showed that inhibition of rolling on P-selectin reduced the adhesion of some clinical parasite isolates to CD36, whereas other parasite isolates appeared to interact directly with CD36. Thus, cytoadherence under physiological flow conditions may be mediated by multiple IRBC ligands that interact with different adhesion molecules in a cooperative fashion. These findings underscore the complexity of the interactions betweeen IRBC and vascular endothelium.


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