Abstract
Clinacanthus nutans (CN) (Acanthaceae) is well-known for its anti-inflammatory properties among Asian communities; however, there are currently no data specifically focused on the anti-inflammatory effects of CN on the brain tissue. Neuroinflammation is a common consequence of toxin intrusion to any part of the central nervous system (CNS). As an innate immune response, the CNS may react through both protective and/or toxic actions due to the activation of neuron cells producing pro- and/or anti-inflammatory cytokines in the brain. The unresolved activation of the inflammatory cytokines’ response is associated with the pathogenesis of neurological disorders. The present study aimed to decipher the metabolic mechanism on the effects of 14 days oral treatment with CN aqueous extract in induced-lipopolysaccharides (LPS) rats through 1H NMR spectroscopic biomarker profiling of the brain tissue and the related cytokines. Based on the principal component analysis (PCA) of the nuclear magnetic resonance (NMR) spectral data, twenty-one metabolites in the brain tissue were profiled as biomarkers for the LPS (10 μL)-induced neuroinflammation following intracerebroventricular injection. Among the twenty-one biomarkers in the neuroinflammed rats, CN treatment of 1000 and 500 mg/kg BW successfully altered lactate, pyruvate, phosphorylcholine, glutamine, and α-ketoglutarate when compared to the negative control. Likewise, statistical isolinear multiple component analysis (SIMCA) showed that treatments by CN and the positive control drug, dextromethorphan (DXM, 5 mg/kg BW), have anti-neuroinflammatory potential. A moderate correlation, in the orthogonal partial least squares (OPLS) regression model, was found between the spectral metabolite profile and the cytokine levels. The current study revealed the existence of high levels of pro-inflammatory cytokines, namely IL-1α, IL-1β, and TNF-α in LPS-induced rats. Both CN dose treatments lowered IL-1β significantly better than DXM Interestingly, DXM and CN treatments both exhibited the upregulation of the anti-inflammatory cytokines IL-2 and 4. However, DXM has an advantage over CN in that the former also increased the expression of IL-10 of anti-inflammatory cytokines. In this study, a metabolomics approach was successfully applied to discover the mechanistic role of CN in controlling the neuroinflammatory conditions through the modulation of complex metabolite interactions in the rat brain.
Highlights
Inflammation is a response by an immune system to either aid or remove a damaging stimulus to facilitate the healing process [1]
A 1H nuclear magnetic resonance (NMR)-based metabolomics approach was applied to assist in the assessment of the anti-inflammatory potential of Clinacanthus nutans (CN) (Fig 2)
principal component analysis (PCA) analysis of the 1H NMR metabolite profile of the brain tissue (Fig 3) revealed the affected metabolic pathways based on both the potential biomarkers of LPS-induced, neuroinflammed condition, and the metabolite alterations caused by CN intervention
Summary
Inflammation is a response by an immune system to either aid or remove a damaging stimulus to facilitate the healing process [1]. Inflammation signals immune cells towards the healing area, enhances blood vessel permeability, and triggers the release of inflammatory mediators [2]. Neuroinflammation is defined as a complex response of any aspect of brain injury which results in the activation of glial cells, and release of inflammatory mediators like cytokines and chemokines, and reactive oxygen and nitrogen species [3]. LPS has been extensively used in in vitro experiments to induce neuroinflammation through the activation of nitrite oxidation and pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6 [8, 9]
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