Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Neuropharmacology Research Laboratory, Jeffrey Cheah, School of Medicine and Health Sciences, Monash University Malaysia, Subang Jaya, Selangor, Malaysia.
PLoS One. 2020 Sep 14;15(9):e0238503. doi: 10.1371/journal.pone.0238503. eCollection 2020.
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.
灵香草（Clinacanthus nutans）（爵床科）在亚洲社区中以其抗炎特性而闻名；然而，目前尚无专门针对灵香草对脑组织的抗炎作用的数据。神经炎症是毒素侵入中枢神经系统（CNS）任何部位的常见后果。作为先天免疫反应，由于神经元细胞的激活，CNS 可能会通过产生促炎和/或抗炎细胞因子产生保护和/或毒性作用。未解决的炎症细胞因子反应的激活与神经疾病的发病机制有关。本研究旨在通过对脑组织的 1 H NMR 光谱生物标志物分析和相关细胞因子，阐明灵香草水提物在诱导脂多糖（LPS）大鼠中 14 天口服治疗的代谢机制。基于核磁共振（NMR）光谱数据的主成分分析（PCA），对侧脑室注射 LPS（10 μL）诱导神经炎症后，在脑组织中对 21 种代谢物进行了生物标志物分析。在神经炎症大鼠的 21 种生物标志物中，与阴性对照相比，灵香草 1000 和 500 mg/kg BW 的治疗成功改变了乳酸盐、丙酮酸、磷酸胆碱、谷氨酰胺和α-酮戊二酸。同样，统计线性多成分分析（SIMCA）表明，灵香草和阳性对照药物右美沙芬（DXM，5 mg/kg BW）的治疗具有抗神经炎症作用。在正交偏最小二乘（OPLS）回归模型中，光谱代谢物谱和细胞因子水平之间存在中度相关性。本研究揭示了 LPS 诱导大鼠中存在高水平的促炎细胞因子，即 IL-1α、IL-1β 和 TNF-α。两种灵香草剂量处理均显著降低了 IL-1β，优于 DXM。有趣的是，DXM 和灵香草处理均上调了抗炎细胞因子 IL-2 和 4。然而，DXM 比灵香草具有优势，因为前者还增加了抗炎细胞因子 IL-10 的表达。在这项研究中，代谢组学方法成功地应用于通过调节大鼠大脑中复杂的代谢物相互作用来发现灵香草控制神经炎症状态的机制作用。
