LPS-induced oxidative inflammation and hyperlipidemia in male rats: The protective role of Origanum majorana extract

The antimicrobicidal activity of the phenolic compounds in the methanolic extract of Origanum majorana was recommended. The present study aimed to investigate the protective effect of Origanum majorana against LPS-induced toxicity in rats. Forty-eight male Sprague-Dawley rats were randomly divided into four equal groups, with 12 rats each group. Group C was used as control, while group E was treated with plant extract orally for 10 days (0.5 mg/kg/day). Group I was given LPS at a single i.p. dose (10 mg/kg BW) and group E + I was treated with plant extract (0.5 mg/kg/day) for 10 days, followed by a single i.p. dose of LPS (10 mg/kg BW). The WBC count and the number of macrophages in addition to the nitric oxide level in the peritoneal fluid were determined. Also, the lipids profile and the levels of urea and creatinine were detected. In addition, the MDA, glutathione and total proteins, as well as AST and ALT activities, were measured in all groups. The results indicated that the LPS injection caused significant decrease in the WBC count, hepatic glutathione and the total proteins, as well as serum HDL-c. On the other hand, LPS injection showed significant increase in the number of peritoneal macrophages, the levels of nitric oxide and MDA. Moreover, the total lipids, total cholesterol, triglycerides, urea, and creatinine concentrations, as well as AST and ALT activities, were significantly elevated. The pretreatment with Origanum majorana extract prior to LPS antagonized and alleviated its toxic effects in the treated animals. The results indicated that the treatment with Origanum majorana extract alone did not affect the tested parameters, except the number of peritoneal macrophages, which were significantly decreased

Alteration of AP-endonuclease1 expression in curcumin-treated fibrotic rats

Background. Apurinic/apyrimidinic endonuclease1/ redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA base excision repair and redox regulation of many transcription factors. It is an important pro-survival protein activated in response to oxidative stress. Increased level of this essential redox sensi¬tive protein correlates closely with cellular survival against oxidative insults. Curcumin (diferuloylmethane) a naturally occurring compound derived from turmeric has attracted interest because of its anti-inflamma¬tory, anti-oxidative, and chemopreventive activities.Material and methods. The current study evaluates the in vivo role of curcumin in protecting and treating liver injury and fibrogenesis caused by carbon tetrachloride (CCl4) in rats. It also addresses the possible involvement of the multifunctional protein APE1 in hepatoprotection. Analysis of APE1 expression was performed at mRNA and protein levels by reverse trans¬criptase (RT)-PCR and western blotting respectively. Profile of HSCs-activation related genes were assayed by RT-PCR and pro-inflammatory cytokines levels were determined by enzyme-linked immune assays.Results. Here we show that oral administration of curcumin was accompanied by a robust increase in APE1 protein and mRNA levels, and improved the histological architecture of rat liver. In addition, curcumin attenuated oxidative stress by increasing the content of hepatic glutathione within normal values, leading to the re¬duction in the level of lipid hydroperoxide. Curcumin remarkably suppressed inflammation by reducing le¬vels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-kB) and interleukin-6 (IL-6). It also inhibited hepatic stellate cells (HSCs) activation by elevating the level of PPARγ and reducing the abundance of transforming growth factor-β (TGF-β). We found that oral adminis¬tration of curcumin at 200 mg/kg dose not only protected against CCl4-induced hepatic injury, but also re¬sulted in more than two-fold induction of APE1 protein expression in CCl4-induced rat group.Conclusions. It can be concluded that curcumin reduced markers of liver damage in rats treated with CCl4, with conco¬mitant elevation in APE1 protein level indicating a possible protective effect with unknown mechanism. The induction of DNA repair enzymes may be an important and novel strategy for hepatic protection against oxidative injury

Novel Hybrid 1,2,4- and 1,2,3-Triazoles Targeting Mycobacterium Tuberculosis Enoyl Acyl Carrier Protein Reductase (InhA): Design, Synthesis, and Molecular Docking

Tuberculosis (TB) caused by Mycobacterium tuberculosis is still a serious public health concern around the world. More treatment strategies or more specific molecular targets have been sought by researchers. One of the most important targets is M. tuberculosis’ enoyl-acyl carrier protein reductase InhA which is considered a promising, well-studied target for anti-tuberculosis medication development. Our team has made it a goal to find new lead structures that could be useful in the creation of new antitubercular drugs. In this study, a new class of 1,2,3- and 1,2,4-triazole hybrid compounds was prepared. Click synthesis was used to afford 1,2,3-triazoles scaffold linked to 1,2,4-triazole by fixable mercaptomethylene linker. The new prepared compounds have been characterized by different spectroscopic tools. The designed compounds were tested in vitro against the InhA enzyme. At 10 nM, the inhibitors 5b, 5c, 7c, 7d, 7e, and 7f successfully and totally (100%) inhibited the InhA enzyme. The IC50 values were calculated using different concentrations. With IC50 values of 0.074 and 0.13 nM, 7c and 7e were the most promising InhA inhibitors. Furthermore, a molecular docking investigation was carried out to support antitubercular activity as well as to analyze the binding manner of the screened compounds with the target InhA enzyme’s binding site

Synthesis and antitumor activity evaluation of some novel pyrazolotriazine derivatives

<p>6-Aminopyrazolo[1,2-<i>a</i>][1,2,4]triazine-4,8-dione derivative <b>3</b> was obtained upon the reaction of the acid hydrazide derivative <b>2a</b> with ethyl cyanoacetate. The reactions of <b>3</b> with several electrophiles such as aldehydes, isatin, acetic anhydride, phenyl isocyanate, benzoyl isothiocyanate, and <i>p</i>-toluenesulfonyl chloride were studied. The structures of the newly synthesized compounds were established on the basis of IR, ¹H NMR, mass spectra, and elemental analyses. The antitumor activities of some selective compounds were examined against two cell lines as liver carcinoma cell line (HEPG-2) and human breast cancer cell line (MCF7).</p