title: Neuroprotective effects of the andrographolide analogue AL-1 in the MPP⁺/MPTP-induced Parkinson's disease model in vitro and in mice.
abstract: The andrographolide-lipoic acid conjugate AL-1 is a newly synthesized molecule by covalently linking andrographolide (Andro) with α-lipoic acid (LA). 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-κB 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-κB activation.
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China.
authors.forename: Zaijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China.
authors.forename: Daoxu
authors.initials: D
authors.lastname: Lai
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenue Padre Tomás Pereira S.J., Macao SAR, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Yu
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China.
authors.forename: Longjun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China.
authors.forename: Baojian
authors.initials: B
authors.lastname: Guo
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China.
authors.forename: Lipeng
authors.initials: L
authors.lastname: Xu
authors.affiliation: Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.
authors.forename: Libing
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China. Electronic address: syw1984@163.com.
authors.forename: Yewei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenue Padre Tomás Pereira S.J., Macao SAR, China. Electronic address: simonlee@umac.mo.
authors.forename: Simon Ming Yuen
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004224:Diterpenes / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020267:MPTP Poisoning / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D011714:Pyrans / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013141:Spiro Compounds / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: C120620:Al 1 spiroketal enol ether epoxide; D004224:Diterpenes; D018696:Neuroprotective Agents; D011714:Pyrans; D013141:Spiro Compounds; C030419:andrographolide
keywords: Andrographolide–lipoic acid conjugate; NF-κB p65; Neuroprotection; Parkinson's disease