Phillygenin activates PKR/eIF2α pathway and induces stress granule to exert anti-avian infectious bronchitis virus

Feng, Haipeng; Zhang, Jingyan; Zhang, Kang; Wang, Xuezhi; Zhang, Kai; Guo, Zhuang; Han, Songwei; Wang, Lei; Qiu, Zhengying; Wang, Guibo; Li, Jianxi

doi:10.1016/j.intimp.2022.108764

Cited by 8 publications

(3 citation statements)

References 45 publications

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“…Compounds capable of modulating the release of glutamate show promise as therapeutic agents for neuroprotection. Phillygenin, a lignan compound from a medicinal herb, has shown promising therapeutic potential due to its effects on inflammation, oxidation, tumors, bacteria, viruses, pain, and liver damage [ 13 , 16 , 20 , 49 ]. Oxidative stress can trigger free radical attack of neuronal cells, which contributes to the development of neurodegenerative disorders.…”

Section: Discussionmentioning

confidence: 99%

“…The pharmacokinetics of phillygenin in rats exhibit first-order kinetics, with rapid distribution and elimination, while in mice, also shows high oral bioavailability, peaking within 30 min [ 11 , 12 ]. Previous studies have shown that phillygenin has diverse biological activities, including anti-inflammatory, antioxidant, antitumor, antibacterial, antiviral, analgesic, and hepatoprotective effects [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Since free radical-induced oxidative damage to the brain is recognized as a primary cause of neuronal death in various neurodegenerative disorders, compounds with antioxidative properties, such as phillygenin, may be effective at preventing or delaying these central nervous system (CNS) disorders [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Phillygenin Suppresses Glutamate Exocytosis in Rat Cerebrocortical Nerve Terminals (Synaptosomes) through the Inhibition of Cav2.2 Calcium Channels

Lee,

Lin,

Chang

et al. 2024

Biomedicines

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Glutamate is a major excitatory neurotransmitter that mediates neuronal damage in acute and chronic brain disorders. The effect and mechanism of phillygenin, a natural compound with neuroprotective potential, on glutamate release in isolated nerve terminals (synaptosomes) prepared from the rat cerebral cortex were examined. In this study, 4-aminopyridine (4-AP), a potassium channel blocker, was utilized to induce the release of glutamate, which was subsequently quantified via a fluorometric assay. Our findings revealed that phillygenin reduced 4-AP-induced glutamate release, and this inhibitory effect was reversed by removing extracellular Ca2+ or inhibiting vesicular transport with bafilomycin A1. However, exposure to the glutamate transporter inhibitor dl-threo-beta-benzyl-oxyaspartate (dl-TOBA) did not influence the inhibitory effect. Moreover, phillygenin did not change the synaptosomal membrane potential but lowered the 4-AP-triggered increase in intrasynaptosomal Ca2+ concentration ([Ca2+]i). Antagonizing Cav2.2 (N-type) calcium channels blocked the inhibition of glutamate release by phillygenin, whereas pretreatment with the mitochondrial Na+/Ca2+ exchanger inhibitor, CGP37157 or the ryanodine receptor inhibitor, dantrolene, both of which block intracellular Ca2+ release, had no effect. The effect of phillygenin on glutamate release triggered by 4-AP was completely abolished when MAPK/ERK inhibitors were applied. Furthermore, phillygenin attenuated the phosphorylation of ERK1/2 and its major presynaptic target, synapsin I, a protein associated with synaptic vesicles. These data collectively suggest that phillygenin mediates the inhibition of evoked glutamate release from synaptosomes primarily by reducing the influx of Ca2+ through Cav2.2 calcium channels, thereby subsequently suppressing the MAPK/ERK/synapsin I signaling cascade.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phillygenin Suppresses Glutamate Exocytosis in Rat Cerebrocortical Nerve Terminals (Synaptosomes) through the Inhibition of Cav2.2 Calcium Channels

Lee,

Lin,

Chang

et al. 2024

Biomedicines

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“…The components that exert the antiviral effect of TCMs are mainly through single components and multiple components [22][23][24]. OCD20015-V009 is an herbal mix of water-extracted Ginseng Radix, Poria (Hoelen), Rehmanniae Radix, Adenophorae Radix, Platycodi Radix, Crataegii Fructus, and Astragali Radix [25], and chlorogenic acid and ginsenoside Rd are the dominant antiviral components that stimulate the antiviral response in murine macrophages and mice to viral infections.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Matrine and Glycyrrhizic Acid on Porcine Reproductive and Respiratory Syndrome Virus in vitro and in vivo

Zhang,

Wu,

et al. 2023

Preprint

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Porcine reproductive and respiratory syndrome is endemic worldwide, seriously affecting development of the pig industry, but vaccine strategies have limited protective effects against PRRSV transmission. The aim of this study was to identify potential anti-PRRSV drugs. We examined the cytotoxicity of seven compounds formulated by the mass ratio between glycyrrhizic acid and matrine and their inhibition rate against PRRSV in vitro. The results showed that the seven compounds all had direct killing and therapeutic effects on PRRSV, and the compounds inhibited PRRSV replication in a time- and dose-dependent manner. Then, the compound with the best anti-PRRSV effect was selected for subsequent in vivo experiments. Pigs were divided into a control group and a medication group to conduct the in vivo evaluation. The results showed that pigs treated with the 4:1 compound had 100% morbidity after PRRSV challenge, and the mortality rate reached 75% on the 8th day of the challenge. These results suggest that this compound has no practical anti-PRRSV effect in vivo and can instead accelerate the death of infected pigs. Next, we further analyzed the semiprotective pigs obtained from the vaccine through the compound to determine whether the compound can synergize with the vaccine in vivo. The results indicated that pigs treated with the compound had higher mortality and more severe clinical reactions after PRRSV infection (p < 0.05). The levels of proinflammatory cytokines (IL-6, IL-8, IL-1β, IFN-γ, TNF-α) were significantly upregulated in the compound-treated pigs compared to the positive control group (p < 0.05), and there was no synergistic enhancement with the live attenuated PRRSV vaccine (p < 0.05). The compound enhanced the inflammatory response, prompted the body to produce excessive inflammatory cytokines and caused body damage, preventing the therapeutic effect from being produced. In conclusion, the present study revealed that effectiveness in vitro does not mean that it is effective in vivo in developing anti-PRRSV drugs. Our finding showed that, in order to find the effective anti-PRRSV drugs, comprehensive drug screening is required, at least with solid anti-inflammatory ability in vitro and in vivo. Our study may help the development of new anti-PRRSV drugs.

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Phillygenin Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis: Suppression of Inflammation and Wnt/β-Catenin Signaling Pathway

et al. 2023

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Phillygenin activates PKR/eIF2α pathway and induces stress granule to exert anti-avian infectious bronchitis virus

Cited by 8 publications

References 45 publications

Phillygenin Suppresses Glutamate Exocytosis in Rat Cerebrocortical Nerve Terminals (Synaptosomes) through the Inhibition of Cav2.2 Calcium Channels

Phillygenin Suppresses Glutamate Exocytosis in Rat Cerebrocortical Nerve Terminals (Synaptosomes) through the Inhibition of Cav2.2 Calcium Channels

The Effect of Matrine and Glycyrrhizic Acid on Porcine Reproductive and Respiratory Syndrome Virus in vitro and in vivo

Phillygenin Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis: Suppression of Inflammation and Wnt/β-Catenin Signaling Pathway

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