S‐allyl cysteine,an active ingredient of garlic,attenuates acute liver dysfunction induced by lipopolysaccharide/ d‐galactosamine in mouse: Underlying mechanisms

In the present study, beneficial effect of S‐allyl cysteine (SAC) was evaluated in the lipopolysaccharide/d ‐galactosamine (LPS/d ‐Gal) model of acute liver injury (ALI). To mimic ALI, LPS and d ‐Gal (50 μg/kg and 400 mg/kg, respectively) were intraperitoneally administered and animals received SAC per os (25 or 100 mg/kg/d) for 3 days till 1 hour before LPS/d ‐Gal injection. Pretreatment of LPS/d ‐Gal group with SAC‐lowered activities of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase and partially reversed inappropriate alterations of hepatic oxidative stress‐ and inflammation‐related biomarkers including liver reactive oxygen species, malondialdehyde, and hepatic activity of the defensive enzyme superoxide dismutase, ferric reducing antioxidant power (FRAP), toll‐like receptor‐4 (TLR4), cyclooxygenase 2, NLR family pyrin domain containing 3 (NLRP3), caspase 1, nuclear factor κB (NF‐κB), interleukin 1β (IL‐1β), IL‐6, tumor necrosis factor‐α, and myeloperoxidase activity. Additionally, SAC was capable to ameliorate apoptotic biomarkers including caspase 3 and DNA fragmentation. In summary, SAC can protect liver against LPS/d ‐Gal by attenuation of neutrophil infiltration, oxidative stress, inflammation, apoptosis, and pyroptosis which is partly linked to its suppression of TLR4/NF‐κB/NLRP3 signaling.     

<Emphasis Type="Italic">Hypericum Perforatum</Emphasis> Hydroalcoholic Extract Mitigates Motor Dysfunction and is Neuroprotective in Intrastriatal 6-Hydroxydopamine Rat Model of Parkinson’s Disease

Parkinson’s disease is the second most common neurodegenerative disorder with selective and progressive decline of nigral dopaminergic neurons. Hypericum perforatum L. (H. perforatum, St. John’s wort) has been traditionally used for management of different disorders, especially mild-to-moderate depression. This study was conducted to evaluate the effect of H. perforatum extract against unilateral striatal 6-hydroxydopamine (6-OHDA) toxicity and to unmask some involved mechanisms. Intrastriatal 6-OHDA-lesioned rats were treated with H. perforatum hydroalcoholic extract at a dose of 200 mg/kg/day started 1 week pre-surgery for 1 week post-surgery. The extract attenuated apomorphine-induced rotational behavior, decreased the latency to initiate and the total time on the narrow beam task, lowered striatal level of malondialdehyde and enhanced striatal catalase activity and reduced glutathione content, normalized striatal expression of glial fibrillary acidic protein, tumor necrosis factor α with no significant effect on mitogen-activated protein kinase, lowered nigral DNA fragmentation, and prevented damage of nigral dopaminergic neurons with a higher striatal tyrosine hydroxylase immunoreactivity. These findings reveal the beneficial effect of H. perforatum via attenuation of DNA fragmentation, astrogliosis, inflammation, and oxidative stress.     

Site-directed mutagenesis and structure-function analysis of the human apolipoprotein A-I. Relation between lecithin-cholesterol acyltransferase activation and lipid binding.

We have mutagenized the human apoA-I gene and have generated cell lines which express normal and mutant apoA-I forms. Point mutations were introduced which changed Gln-1, Gln-2 to Arg,Arg, Pro99 to His, and Pro121 to His. In addition, the following amino acid deletions (delta) were generated: delta 113-124, delta 148-186, delta 212-233, and delta 213-243. The apoA-I form isolated from the culture medium of C127 cells was analyzed for its ability to activate lecithin-cholesterol acyltransferase (LCAT) and to bind to phospholipid vesicles and high density lipoprotein (HDL). Compared with the wild type (WT) apoA-I, the relative activation of LCAT achieved by the point mutations Gln-1, Gln-2----Arg,Arg, Pro99----His, and Pro121----His were 106 +/- 7, 92 +/- 6, and 77 +/- 9%, respectively. Kinetic analysis of one mutant apoA-I form showed similar Vmax but a 15-fold increase in the Km of the mutant apoA-I form. Furthermore, the activation achieved by the internal deletion mutants delta 113-124, delta 148-186, delta 212-233, and delta 213-243 was 47 +/- 3, 0.5 +/- 0.4, 28 +/- 4 and 13 +/- 5%, respectively. Mutants deficient in their ability to activate LCAT displayed alterations in liposome and HDL binding, compared with WT as determined by density gradient ultracentrifugation analysis of the culture medium. Thus, the peak recovery (approximately 50%) of apoA-I bound to HDL was at density 1.14 g/ml for the WT apoA-I, at 1.18 g/ml for the mutants delta 113-124 and delta 148-186, and at d greater than 1.21 g/ml for the delta 212-233 and delta 213-243. Electron microscopy of the proteoliposome LCAT substrate generated by WT and mutant apoA-I forms showed that the carboxyl-terminal deletion mutants which displayed aberrant binding to HDL also displayed reduced ability to convert the spherical lecithin-cholesterol vesicles into discs compared with WT. The findings suggest that (a) the importance of the carboxyl terminus of apoA-I for LCAT activation is related to its ability to bind to lipid and/or to form discoidal substrate for LCAT, and (b) the interaction of several domains of apoA-I are required for the activation of LCAT.     

Netrin-1 protects the SH-SY5Y cells against amyloid beta neurotoxicity through NF-κB/Nrf2 dependent mechanism

Molecular Biology Reports - Many evidence confirms that amyloid beta 1–42 fragment (Aβ1–42) causes neuroinflammation, oxidative stress, and cell death, which are related to...     

Isolation from human cerebrospinal fluid of a new insulin-like growth factor-binding protein with a selective affinity for IGF-II

In biological fluids IGF-I and IGF-II are bound to specific, high-affinity binding protein (BPs). Two human BPs have been isolated, one from serum, which is GH-dependent, the other from amniotic fluid (AF BP), and their cDNAs have recently been cloned. We report here the isolation of another, new species from cerebrospinal fluid (CSF) where this BP predominates. The protein was purified to homogeneity by a four-step procedure: gel filtration, chromatofocusing, hydrophobic-interaction chromatography and reverse-phase chromatography. Thereafter, SDS-polyacrylamide gel electrophoresis gave an Mr of 34,000 (non-reduced), chromatofocusing gave an isoelectric point of 5.0m and its affinity for IGF-II (3 x 10(10) M-1) was 10 times that for IGF-I. The N-terminal amino acid sequence of the first 15 residues determined in a BP preparation from the CSF of children was Leu-Ala-Pro-Gly-(/)-Gly-Gln-Gly-Val-Gln-Ala-Gly-Ala-Pro-Gly. A similar sequence was found for adult CSF, apart from residues 12 and 13 (-Leu-Leu-). These are highly analogous with the sequences starting from residue 69 of the GH-dependent BP, and from residue 61 of the AF BP. The new BP isolated is therefore related to, but distinct from, the other human BPs.