Cerebrolysin attenuates cerebral and hepatic injury due to lipopolysaccharide in rats

Abstract

This study aimed to investigate the effect of cerebrolysin on oxidative stress in the brain and liver during systemic inflammation. Rats were intraperitoneally challenged with a single subseptic dose of lipopolysaccharide (LPS; 300 μg/kg) without or with cerebrolysin at doses of 21.5, 43 or 86 mg/kg. After 4 h, rats were euthanized and the brain and liver tissues were subjected to biochemical and histopathological analyses. Cerebrolysin revealed inhibitory effects on the elevation of lipid peroxidation and nitric oxide induced by LPS. In contrast, the decrease in reduced glutathione level and paraoxonase activity induced by LPS was attenuated by an injection of cerebrolysin in a dose-dependent manner. Moreover, cerebrolysin reduced LPS-induced activation of brain NF-κB and reversed LPS-induced decline of brain butyrylcholinesterase and acetylcholinesterase activities in a dose-dependent manner. Histopathological analyses revealed that neuronal damage and liver necrosis induced by LPS were ameliorated by cerebrolysin dose-dependently. Cerebrolysin treatment dose-dependently attenuated LPS-induced expressions in cyclooxygenase 2, inducible nitric oxide synthase, and caspase-3 in the cortex or striatum as well as the liver. These results suggest that cerebrolysin treatment might have beneficial therapeutic effects in cerebral inflammation. Cerebrolysin might also prove of value in liver disease and this possibility requires further exploration.

Neuromodulatory Activity of Dietary Phenolics Derived from Corchorus olitorius L.

“…This is in accordance with the previously reported activation of NF‐κB pathway and COX‐2 expression in the brain of rats upon i.p. LPS injection (Abdel‐Salam et al., ). Co administration prior to LPS injection slightly attenuated COX‐2 expression in mice brains and to the best of our knowledge, the effect of Co on brain COX‐2 has not been previously assessed in vivo .…”

Cerebrolysin in the therapy of mild cognitive impairment and dementia due to Alzheimer's disease: 30 years of clinical use

“…Cerebrolysin counteracts LPS‐induced changes in brain NF‐κB, JNK, and p38‐MAPK signaling, improving brain recovery and functioning 157,158 . These signaling pathways contributed to the switch of microglia to an anti‐inflammatory phenotype and to the decrease of inflammation factors (TNF‐α and IL‐1β), and might also be involved in the anti‐inflammatory effects of Cerebrolysin in other experimental conditions and in AD patients 159–165 …”

“…Treatment with Cerebrolysin is also mechanistically associated with changes in several other molecular pathways of pathological relevance in AD. The neuroprotective effects of Cerebrolysin in different models of excitotoxicity and oxidative stress have been related to its reversible inhibition of calpain, 142,164,177–179 and to its influence on lipid peroxidation and antioxidants 142,153,157,164,180–185 . Cerebrolysin also modulates substrates, enzymes, and receptors implicated in glutamatergic, GABAergic, and cholinergic transmission 142,157,164,166,179,186–190 .…”

“…The neuroprotective effects of Cerebrolysin in different models of excitotoxicity and oxidative stress have been related to its reversible inhibition of calpain, 142,164,177–179 and to its influence on lipid peroxidation and antioxidants 142,153,157,164,180–185 . Cerebrolysin also modulates substrates, enzymes, and receptors implicated in glutamatergic, GABAergic, and cholinergic transmission 142,157,164,166,179,186–190 . The expression of GLUT1 glucose transporter and the transport of glucose through the BBB were also enhanced by Cerebrolysin 142,191,192 .…”

Peptide profiling of Internet‐obtained Cerebrolysin using high performance liquid chromatography – electrospray ionization ion trap and ultra high performance liquid chromatography – ion mobility – quadrupole time of flight mass spectrometry

“…The product, first developed in Russia a few decades ago, is claimed to have a positive effect on various central disorders like ischemic stroke and vascular dementia . In vitro experiments on cells, as well as in vivo animal experiments and human clinical trials, report various effects, with a high number of results written in Russian and published in local journals; several other studies are sponsored by or done in collaboration with the manufacturer . Despite this research, meta‐analysis of the currently available vascular dementia and ischemic stroke clinical trials data indicate that there is not enough evidence to recommend the medicine as a general evidence‐based standard therapy for these diseases .…”