Neuroprotective and Anti—Neuroinflammatory Effects of a Poisonous Plant Croton tiglium Linn. Extract

Abstract

Neuroinflammation is involved in various neurological diseases. Activated microglia secrete many pro-inflammatory factors and induce neuronal cell death. Thus, the inhibition of excessive proinflammatory activity of microglia leads to a therapeutic effect that alleviates the progression of neuronal degeneration. In this study, we investigated the effect of Croton tiglium (C. tiglium) Linn. extract (CTE) on the production of pro- and anti-inflammatory mediators in microglia and astrocytes via RT-PCR, Western blot, and nitric oxide assay. Neurotoxicity was measured by cell viability assay and GFP image analysis. Phagocytosis of microglia was measured using fluorescent zymosan particles. CTE significantly inhibited the production of neurotoxic inflammatory factors, including nitric oxide and tumor necrosis factor-α. In addition, CTE increased the production of the neurotrophic factor, brain-derived neurotrophic factor, and the M2 phenotype of microglia. The culture medium retained after CTE treatment increased the survival of neurons, thereby indicating the neuroprotective effect of CTE. Our findings indicated that CTE inhibited pro-inflammatory response and increased the neuroprotective ability of microglia. In conclusion, although CTE is known to be a poisonous plant and listed on the FDA poisonous plant database, it can be used as a medicine if the amount is properly controlled. Our results suggested the potential benefits of CTE as a therapeutic agent for different neurodegenerative disorders involving neuroinflammation.

Anti-Inflammatory Effects of Dimethyl Fumarate in Microglia via an Autophagy Dependent Pathway

“…BV-2 cells, an immortalized murine microglial cell line, were maintained in DMEM supplemented with 5% FBS and 100 U/mL penicillin/ streptomycin. Primary mixed glial cells (MGC) were prepared from neonatal C57BL/6 mice on postnatal days 1-3, as previously described (Gupta et al, 2020), with minor modifications. The cell suspensions obtained from brain tissue dissection were cultured with DMEM supplemented with 10% FBS and 100 U/mL penicillin/streptomycin for three weeks, with medium changed every three days.…”

“…On the other hand, IL-4, IL-10, and IL-13 induce the microglial switch to the M2 state, wherein they release anti-inflammatory cytokines such as IL-4, IL-10, IL-13, and transforming growth factor-beta and increase the expression levels of arginase-1, brain-derived neurotrophic factor, and Ym1; the M2 microglia are recognized for their increased neuroprotective capacity. Thus, M1 and M2 microglia are involved in pathogenic and neuroprotective responses, respectively (Song et al, 2016;Song and Suk, 2017;Gupta et al, 2020).…”

Fluoxetine Potentiates Phagocytosis and Autophagy in Microglia

“…Primary mixed glial cells (MGCs) were prepared from neonatal C57BL/6 mice on postnatal days 1-3, as previously described (Gupta et al, 2020), with minor modifications. All experiments were conducted in accordance with the institutional animal care committee of the Catholic Kwandong University (no.…”

“…Among them, there are neurotrophic factors that affect the survival of neurons and have neuroprotective effects (Song et al, 2016a;Song et al, 2016b;Ramirez et al, 2017). Activated microglia also produce many proinflammatory and neurotoxic factors (Jha et al, 2018;Song et al, 2019;Gupta et al, 2020). These proinflammatory cytokines and molecules produced by these inflammatory activated microglia cause neuroinflammation, which can lead to neurodegenerative diseases (Ramirez et al, 2017;Hansen et al, 2018).…”

Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activation

“…Crotonoside is the most abundant croton alkaloid extracted from seeds of Croton tiglium L. and active ingredients from Croton tiglium extract exhibits a wide variety of bioactivities that have been traditionally exploited for many indications, such as constipation, headache, abdominal and stomach pain, inflammation, and rheumatism and [9][10][11][12][13]. A more recent study revealed that seed extract suppressed the inflammatory responses elicited by LPS on microglia and astrocytes via inhibiting nitric oxide and tumor necrosis factor-α (TNF-α) and polarized microglia toward the M2 phenotype, potentially providing neuroprotectivie effects [14]. Additionally, crotonoside has been reported to be capable of suppressing acute myeloid leukemia via inhibiting Fms-like tyrosine kinase 3 (Flt3) and HDAC3/6 pathways [15].…”