Phikud Navakot extract attenuates lipopolysaccharide-induced inflammatory responses through inhibition of ERK1/2 phosphorylation in a coculture system of microglia and neuronal cells. (5th October 2022)

• Record Type: Journal Article
• Authors: Temviriyanukul, Piya; Lertmongkolaksorn, Thanapat; Supasawat, Punchaya; Pitchakarn, Pornsiri; Thiyajai, Parunya; Nusuetrong, Punnee; Phochantachinda, Sataporn; Chansawhang, Anchana; Chantong, Boonrat
• Is Part Of: Journal of ethnopharmacology. Volume 296(2022)
• Publication Date: 2022-10-05
• Subjects: Phikud Navakot -- Neuroinflammation -- Gallic acid -- Mitogen-activated protein kinases pathway -- Microglia; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.115440
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Phikud Navakot (PN), a mixture of nine herbal plants, is an ancient Thai traditional medicine used for relieving circulatory disorders and dizziness. PN has also shown anti-inflammatory effects in rats with acute myocardial infarction. Moreover, phytochemical-inhibiting neuroinflammation, including gallic acid, vanillic acid, ferulic acid, and rutin were detected in PN extract; however, the anti-neuroinflammatory activity of PN extract and its components in a coculture system of microglia and neuronal cells is limited. Objective: To investigate the anti-neuroinflammatory activities of PN on lipopolysaccharide (LPS)-induced inflammation in a coculture system of microglia and neuronal cells. Methods: ELISA and qRT-PCR were used to assess cytokine expression. The phosphorylation of mitogen-activated protein kinases (MAPKs) was determined by Western blotting. Microglia-mediated neuroinflammation was evaluated using a BV-2 microglia-N2a neuron transwell co-culture. Results: PN extract and its component, gallic acid, decreased LPS-induced the mRNA expression of interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), as well as IL-6 protein levels in both microglial monoculture and coculture systems. This was accompanied by a reduction in neurodegeneration triggered by microglia in N2a neurons with increased neuronal integrity markers (βIII tubulin and tyrosine hydroxylase (TH)). These effects were caused by the ability of PN extract to inhibit extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) activation. Conclusion: This is the first study to show that PN extract inhibits neurodegeneration in LPS-activated BV-2 microglia by targeting ERK signaling activity. Graphical abstract: Image 1 Highlights: Phikud Navakot (PN) extract decreases inflammation in microglia monoculture and neuron-microglia coculture. PN enhances neuronal markers in neuronal monoculture and neuron-microglia coculture following lipopolysaccharide exposure. PN inhibits ERK1/2 phosphorylation in a coculture system of microglia and neuronal cells.