Andrographolide Treatment Lessens Localized, Systemic Inflammation and Improves Other Pathophysiological Traits in a Mouse Model of Gulf War Illness

Gulf War Illness (GWI) is a chronic multi-symptom disorder that affected almost one-third of the deployed veterans during first Persian (1990-91). Symptoms include gastrointestinal disturbances, fatigue, cognitive deficiencies, and neuroinflammation. Our group has recently shown series different therapeutic strategies span oral butyrate, anti-viral drug Ribavirin, TLR4 antagonist Sparstolonin B effectively improving outcomes to murine GWI-linked symptoms. Andrographolide (AG), labdane diterpenoid produced by plant Andrographis paniculata, exerts numerous beneficial effects in various cell types. Adult C57BL/6J mice were exposed GWI chemicals (GWC) pyridostigmine bromide permethrin for week (GWT group) simultaneously treated with AG (GWT+AG group). In our previous report, virome dysbiosis showed strong association inflammation. Next-Gen Sequencing data both richness Shannon diversity markedly altered GWT+AG than GWT mice. The observed increased relative abundance Siphoviridae, Myoviridae, decreased Microviridae was reversed treatment, referring restored gut environment. Gut leaching marked Occludin expression Claudin2 likely consequence induced decrease TLR7 expression. administration barrier integrity, activation, NFκb phosphorylation, Furthermore, systemic inflammation mice, evidenced high level serum IL-1β IL-6, found be Blood-brain (BBB) integrity loss resulting microglial common feature pathology treatment. dysfunctional BBB enhancing tight junction protein Claudin5 as well activation. Also, led brain-derived neurotrophic factor (BDNF) frontal cortex, molecule pronounced role synaptic plasticity neuronal regeneration. summary, these results explicitly imply played key decreasing GWI-associated intestinal, systemic, neuroinflammation whereas it also improved intestinal mouse model.