Herpetosiphon secondary metabolites inhibit amyloid-β toxicity in human primary astrocytes

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Abstract

Background: The accumulation of extracellular plaques containing amyloid-β protein (Aβ) in the brain is one of the main pathological hallmarks of Alzheimer's disease (AD). Aβ peptide can promote the production of highly volatile free radicals and reactive oxygen species (ROS) that can induce oxidative damage to neurons and astrocytes. At present, numerous studies have investigated the neuroprotective and glioprotective effects of natural products derived from plants, animals, and microorganisms. Objective: We investigated the glioprotective effect of secondary metabolites obtained from Herpetosiphon sp. HM 1988 against Aβ40-induced toxicity in human primary astrocytes. Methods: The protective effect of bacterial secondary metabolites against Aβ40-induced inducible nitric oxide synthase (iNOS) activity was evaluated using the citrulline assay. To confirm the iNOS activity, nitrite production was assessed using the fluorometric Griess diazotization assay. Intracellular NAD+ depletion and lactate dehydrogenase (LDH) release in human primary astrocytes were also examined using well-established spectrophotometric assays. Results: Our results indicate that Aβ40 can induce elevation in iNOS and LDH activities, nitrite production, and cellular energy depletion. Importantly, extract of Herpetosiphon sp. HM 1988 decreased iNOS activity, nitrite production, and LDH release. In addition, metabolites of the strain were able to restore cellular energy deficits through inhibition of NAD+ depletion mediated by Aβ40. Conclusion: These findings suggest that Herpetosiphon metabolites may represent a promising, novel source for the prevention of Aβ toxicity in AD.

Original languageEnglish
Pages (from-to)423-433
Number of pages11
JournalJournal of Alzheimer's Disease
Volume76
Issue number1
DOIs
Publication statusPublished - 1 Jan 2020

Keywords

  • Alzheimer’s disease
  • amyloid-β
  • Herpetosiphon
  • inducible nitric oxide synthase
  • natural products
  • oxidative stress

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