Neuroprotection of Andrographolide Against Microglia-Mediated Inflammatory Injury and Oxidative Damage in PC12 Neurons.

Abstract

Andrographolide from leaves of Andrographis paniculata has been known to possess various bioactivities. In the present study, we aimed to explore the neuroprotection of andrographolide against inflammation-mediated injury and oxidative damage. In initial studies, our findings showed that pretreatment with andrographolide could effectively reduce neuronal cell death caused by LPS-induced conditioned supernatants. The further results indicated that this neuroprotective effect may be mainly due to the inhibition on the production of NO, TNF-α, IL-6, ROS, iNOS and enhancement of expression of anti-inflammatory marker CD206. Moreover, mechanism study revealed that the anti-inflammatory activity of andrographolide may be related to the suppression of nuclear translocation of NF-κB as well as the activation of Nrf2 and HO-1. Our study also showed that andrographolide could scavenge ROS and protect PC12 cells against H2O2- and 6-OHDA-mediated oxidative damage. In addition, several derivatives of andrographolide were prepared for evaluating the role of 3, 14, 19-hydroxy group on anti-inflammatory effect and cytoprotection of andrographolide. In conclusion, andrographolide protected neurons against inflammation-mediated injury via NF-κB inhibition and Nrf2/HO-1 activation and resisted oxidative damage via inhibiting ROS production. Our results will contribute to further exploration of the therapeutic potential of andrographolide in relation to neuroinflammation and neurodegenerative diseases.

• Authors: Yuanzhen Xu, Dan Tang, Jianping Wang, Hongbo Wei, Jinming Gao
• Journal: Neurochemical research (Neurochem Res) Vol. 44 Issue 11 Pg. 2619-2630 (Nov 2019) ISSN: 1573-6903 [Electronic] United States
• PMID: 31562575 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Diterpenes
• Lipopolysaccharides
• Membrane Proteins
• NF-E2-Related Factor 2
• NF-kappa B p50 Subunit
• Neuroprotective Agents
• Nfe2l2 protein, mouse
• Nfkb1 protein, mouse
• Nitric Oxide
• andrographolide
• Hydrogen Peroxide
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Heme Oxygenase-1
• Hmox1 protein, mouse

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Diterpenes (pharmacology)
• Heme Oxygenase-1 (metabolism)
• Hydrogen Peroxide (metabolism)
• Inflammation (drug therapy)
• Lipopolysaccharides
• Membrane Proteins (metabolism)
• Mice
• Microglia (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B p50 Subunit (metabolism)
• Neuroprotective Agents (pharmacology)
• Neurotoxicity Syndromes (drug therapy)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Oxidative Stress (drug effects)
• PC12 Cells
• Rats