Andrographolide - A promising therapeutic agent, negatively regulates glial cell derived neurodegeneration of prefrontal cortex, hippocampus and working memory impairment.

Abstract

Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region. Active microglial and reactive astrocytic makers were also downregulated after andrographolide treatment. Andrographolide suppressed overexpression of microglial MIP-1α, P2X7 receptor and its downstream signaling mediators including-inflammasome NLRP3, caspase1 and mature IL-1β. Furthermore, in vivo maze studies suggested that andrographolide treatment reversed LPS-induced behavioural and working memory disturbances including regulation of expression of protein markers like PKC, p-CREB, amyloid beta, APP, p-tau, synapsin and PSD-95. Andrographolide, by lowering expression of pro apoptotic genes and enhancing the expression of anti-apoptotic gene showed its anti-apoptotic nature that in turn reduces neurodegeneration. Morphology studies using Nissl and FJB staining also showed the neuroprotective effect of andrographolide in the prefrontal cortex region. The above studies indicated that andrographolide prevented neuroinflammation-associated neurodegeneration and improved synaptic plasticity markers in cortical as well as hippocampal region which suggests that andrographolide could be a novel pharmacological countermeasure for the treatment of neuroinflammation and neurological disorders related to memory impairment.

• Authors: Sudeshna Das, K P Mishra, Lilly Ganju, S B Singh
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 313 Pg. 161-175 (12 15 2017) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 29146293 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Diterpenes
• Glial Fibrillary Acidic Protein
• Inflammation Mediators
• Polysaccharides
• Tlr4 protein, rat
• Toll-Like Receptor 4
• andrographolide
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Ptgs2 protein, rat

Topics

• Animals
• Animals, Newborn
• Anti-Inflammatory Agents (pharmacology)
• Cyclooxygenase 2 (metabolism)
• Cytokines (metabolism)
• Diterpenes (pharmacology)
• Glial Fibrillary Acidic Protein (metabolism)
• Hippocampus (drug effects, metabolism)
• Inflammation Mediators (metabolism)
• Male
• Maze Learning (drug effects)
• Memory Disorders (chemically induced, drug therapy)
• Memory, Short-Term (drug effects)
• Mice
• Mice, Inbred BALB C
• Nitric Oxide Synthase Type II (metabolism)
• Polysaccharides (toxicity)
• Prefrontal Cortex (drug effects, metabolism)
• Rats
• Toll-Like Receptor 4 (metabolism)