TY - JOUR
T1 - The anti-neuroinflammatory effects of Clinacanthus nutans leaf extract on metabolism elucidated through 1H NMR in correlation with cytokines microarray
AU - Azam, Amalina Ahmad
AU - Ismail, Intan Safinar
AU - Kumari, Yatinesh
AU - Shaikh, Mohd Farooq
AU - Abas, Faridah
AU - Shaari, Khozirah
N1 - Funding Information:
ISI. Ministry of Agriculture and Agrobased Industry, Malaysia, under NKEA Research Grant scheme (NRGS: project No. NH1014D070).
Publisher Copyright:
© 2020 Ahmad Azam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/9/14
Y1 - 2020/9/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85091052833&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0238503
DO - 10.1371/journal.pone.0238503
M3 - Article
C2 - 32925968
AN - SCOPUS:85091052833
SN - 1932-6203
VL - 15
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e0238503
ER -