Berberine Ameliorates Lipopolysaccharide-Induced Cognitive Impairment Through SIRT1/NRF2/NF-κB Signaling Pathway in C57BL/6J Mice.

The inflammatory response is the stress reactions to infection or injury so as to help the body return to normal as soon as possible. In central nervous system, the overactivated immune system causes irreversible damage to neurons and synapses, which results in cognitive impairment. Berberine, an isoquinoline alkaloid extracted from Coptidis Rhizoma, plays a powerful role in anti-inflammation. It has been reported that berberine significantly improved the decline of cognitive ability. Therefore, we carried out this work to find out the specific mechanism. We tested behaviorally that berberine administration did improve lipopolysaccharide (LPS)-induced cognitive impairment in C57BL/6J mice. We found that berberine reduced neuronal damage in the hippocampus by Nissl staining, and verified by western blot and immunofluorescence that berberine improved LPS-induced cognitive impairment through the SIRT1/nuclear factor E2-related factor 2 (NRF2)/nuclear factor-kappaB (NF-κB) signaling pathway. The results showed that berberine plays an anti-inflammatory and antioxidant role by targeting SIRT1/NRF2/NF-κB signaling pathway so as to reduce the cognitive impairment and neuronal damage caused by LPS in C57BL/6J mice. Berberine preprotection increased the expression of heme oxygenase-1 (HO-1) after activating NRF2 and inhibited the activation of NF-κB and the release of inducible NO synthase, which may be related to berberine activating SIRT1. However, the effect of reducing inflammatory response was inhibited after using SIRT1 inhibitor EX527 in vitro. This research explains the significance of anti-inflammatory in the treatment of cognitive impairment from different angles.

In vitro and in vivo identification of a novel cytotoxic T lymphocyte epitope from Rv3425 of Mycobacterium tuberculosis.

The identification of novel cytotoxic T lymphocyte (CTL) epitopes is important to analysis of the involvement of CD8(+) T cells in Mycobacterium tuberculosis infection as well as to the development of peptide vaccines. In this study, a novel CTL epitope from region of difference 11 encoded antigen Rv3425 was identified. Epitopes were predicted by the reversal immunology approach. Rv3425-p118 (LIASNVAGV) was identified as having relatively strong binding affinity and stability towards the HLA-A*0201 molecule. Peripheral blood mononuclear cells pulsed by this peptide were able to release interferon-γ in healthy donors (HLA-A*02(+) purified protein derivative(+)). In cytotoxicity assays in vitro and in vivo, Rv3425-p118 induced CTLs to specifically lyse the target cells. Therefore, this epitope could provide a subunit component for designing vaccines against Mycobacterium tuberculosis.

Identification of novel T cell epitopes from efflux pumps of Mycobacterium tuberculosis.

Cytotoxic T lymphocytes (CTLs) play an important role in the immunity of Mycobacterium tuberculosis (Mtb) infection. In the present study, the identification of novel CTL epitopes from efflux pumps, Rv1258c and Rv1410c, was reported. Candidate native peptides and their analogues were predicted with prediction programs. Rv1410c-p510 (TLAPQVEPL) and Rv1410c-p510-1Y9V (YLAPQVEPV) showed potent binding affinity and stability towards HLA-A*0201 molecule. In enzyme-linked immunospot (ELISPOT) assay, the CTLs induced from peripheral blood mononuclear cells (PBMCs) by these peptides could release interferon-γ (IFN-γ) in at least one healthy donor (HLA-A*02(+), PPD(+)). In cytotoxicity assay in vitro and in vivo, the CTLs induced by Rv1410c-p510-1Y9V could specifically lyse peptide-loaded T2 cells. This is the first report to identify CTL epitopes from the efflux pumps of Mtb. The novel epitope identified could serve as candidate to the multivalent peptide vaccine against drug-resistant M. tuberculosis.