Centipeda minima extract exerts antineuroinflammatory effects via the inhibition of NF-κB signaling pathway

• Published in: Phytomedicine (Stuttgart) Vol. 67; p. 153164
• Main Authors: Li, Si-Yi, Zhou, Yi-Le, He, Dan-Hua, Liu, Wei, Fan, Xiang-Zhen, Wang, Qi, Pan, Hua-Feng, Cheng, Yong-Xian, Liu, Yong-Qiang
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.02.2020
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Asteraceae - chemistry; Centipeda minima; Dinoprostone - metabolism; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; ECM; Enzymes - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; inflammatory enzymes; Lipopolysaccharides - pharmacology; Male; Mice, Inbred C57BL; Microglia - cytology; Microglia - drug effects; Microglia - metabolism; Neuroinflammation; NF-kappa B - metabolism; NF-κB; Plant Extracts - chemistry; Plant Extracts - pharmacology; Proinflammatory mediators; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; Tandem Mass Spectrometry; Tumor Necrosis Factor-alpha - metabolism; C. minima; PGE2; IκB-α; Centipeda minima; Neuroinflammation; CNS; Iba1; IL-1β; ECM; LPS; NF-κB; Proinflammatory mediators; HPLC-MS/MS; TNF-α; DEX; ROS; COX2; iNOS; NOX4; inflammatory enzymes; NOX2
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2019.153164

Centipeda minima (L.) A.Br. (C. minima) has been used in traditional Chinese herbal medicine to treat nasal allergy, diarrhea, asthma and malaria for centuries. Recent pharmacological studies have demonstrated that the ethanol extract of C. minima (ECM) and several active components possess anti-bacterial, anti-arthritis and anti-inflammatory properties. However, the effects of ECM on neuroinflammation and the underlying mechanisms have never been reported. The study aimed to examine the potential inhibitory effects of ECM on neuroinflammation and illustrate the underlying mechanisms. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was performed to qualify the major components of ECM; BV2 and primary microglial cells were used to examine the anti-inflammatory activity of ECM in vitro. To evaluate the anti-inflammatory effects of ECM in vivo, the mice were orally administrated with ECM (100, 200 mg•kg−1•d−1) for 2 days before cotreatment with LPS (2 mg•kg−1•d−1, ip) for an additional 3 days. The mice were sacrificed the day after the last treatment and the hippocampus was dissected for further experiments. The expression of inflammatory proteins and the activation of microglia were respectively detected by real-time PCR, ELISA, Western blotting and immunofluorescence. HPLC-MS/MS analysis confirmed and quantified seven chemicals in ECM. In BV2 and primary microglial cells, ECM inhibited the LPS-induced production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), thus protecting HT22 neuronal cells from inflammatory damage. Furthermore, ECM inhibited the LPS-induced activation of NF-κB signaling pathway and subsequently attenuated the induction of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), NADPH oxidase 2 (NOX2) and NADPH oxidase 4 (NOX4), leading to the decreased production of nitrite oxide, prostaglandin E2 (PGE2) and reactive oxygen species (ROS). In an LPS-induced neuroinflammatory mouse model, ECM was found to exert anti-inflammatory activity by decreasing the production of proinflammatory mediators, inhibiting the phosphorylation of NF-κB, and reducing the expression of COX2, iNOS, NOX2 and NOX4 in the hippocampal tissue. Moreover, LPS-induced microglial activation was markedly attenuated in the hippocampus, while ECM at a high dose possesses a stronger anti-inflammatory activity than the positive drug dexamethansone (DEX). These findings demonstrate that ECM exerts antineuroinflammatory effects via attenuating the activation of NF-κB signaling pathway and inhibiting the production of proinflammatory mediators both in vitro and in vivo. C. minima might become a novel phytomedicine to treat neuroinflammatory diseases. [Display omitted]