Neuroprotective effects of the andrographolide analogue AL-1 in the MPP+/MPTP-induced Parkinson's disease model in vitro and in mice

The andrographolide-lipoic acid conjugate AL-1 is a newly synthesized molecule by covalently linking andrographolide (Andro) with alpha-lipoic acid (IA). In the present work, the neuroprotective effect of AL-1 was investigated in vitro and in a mouse model of the Parkinson's disease (PD). We found that AL-1 significantly prevented 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in SH-SY5Y cells and primary cerebellar granule neurons. In a mouse model of Parkinson's disease, AL-1 rescued 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced loss of tyrosine hydroxylase (TH)-positive neurons, improved the behavioral impairment, and elevated the striatal levels of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid. Furthermore, AL-1 remarkably lowered the nitric oxide and malondialdehyde levels while increased the superoxide dismutase level in the substantial nigra of MPTP-treated mice. The immunoblotting data showed that AL-1 significantly ameliorated the decreased expression of TH protein in the substantial nigra and inhibited the up-regulation of phosphorylated NF-kappa B p65 in vitro and in vivo. Taken together, AL-1 exerted neuroprotective effect in vitro and in animal model of PD through anti-oxidation and inhibition of NF-kappa B activation. (C) 2014 Elsevier Inc. All rights reserved.