Effect of eleutheroside B1 on non‑coding RNAs and protein profiles of influenza A virus‑infected A549 cells

Abstract

Influenza viruses often pose a serious threat to animals and human health. In an attempt to explore the potential of herbal medicine as a treatment for influenza virus infection, eleutheroside B1, a coumarin compound extracted from herba sarcandrae, was identified, which exhibited antiviral and anti-inflammatory activities against influenza A virus. In this study, high-throughput RNA sequencing and isobaric tags for relative and absolute quantification (iTRAQ) assays were performed to determine alterations in the non-coding RNA (ncRNA) transcriptome and proteomics. Bioinformatics and target prediction analyses were used to decipher the potential roles of altered ncRNAs in the function of eleutheroside B1. Furthermore, long ncRNA (lncRNA) and mRNA co-expressing networks were constructed to analyze the biological functions by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The analysis of RNA sequencing data revealed that 5 differentially expressed ncRNAs were upregulated and 3 ncRNAs were downregulated in the A549 cells infected with A/PR8/34/H1N1, with or without eleutheroside B1 treatment (PR8+eleu and PR8, respectively). Nuclear paraspeckle assembly transcript 1 (NEAT1) was differentially expressed between the PR8 and A549 cell groups. GO and KEGG pathway analyses indicated that eleutheroside B1 took advantage of the host cell biological processes and molecular function for its antiviral and anti-inflammatory activities, as well as for regulating cytokine-cytokine receptor interaction in the immune system, consistent with previous findings. The results of the iTRAQ assays indicated that L antigen family member 3 (LAGE3) protein, essential for tRNA processing, tRNA metabolic processes and ncRNA processing, was downregulated in the PR8+eleu compared with the PR8 group. In the present study, these comprehensive, large-scale data analysis enhanced the understanding of multiple aspects of the transcriptome and proteomics that are involved in the antiviral and anti-inflammatory activities of eleutheroside B1. These findings demonstrate the potential of eleutheroside B1 for use in the prevention and treatment of influenza A virus-mediated infections.

Efficacy of Kan Jang® in Patients with Mild COVID-19: Interim Analysis of a Randomized, Quadruple-Blind, Placebo-Controlled Trial

“…Furthermore, they agree with preclinical in vitro and in vivo studies of Andrographis paniculata and Eleutherococcus senticosus preparations [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Antiviral activity of Eleutherococcus extracts were demonstrated in experimental model systems in which rodents were infected with H1N1 influenza A virus [23][24][25][26], human rhinovirus and respiratory syncytial virus [24]. The antiviral effect of Andrographis extracts [27] were demonstrated against H1N1 influenza A [28-30], H5N1 avian influenza [31], Chikungunya [32] Dengue [33,34], and SARS-CoV-2 [35][36][37][38] viruses.…”

“…These results are in line with the results of a prospective, multicenter, open-label, and randomized controlled trial of Xiyanping intravenous injection (iso-andrographolide-19sodium sulfate, a synthetic derivative of andrographolide, the primary anti-inflammatory compound of Herbal Andrographidis) in patients with mild to moderate COVID-19, where significant reduction in the time to cough relief, fever resolution and virus clearance were demonstrated [17]. Furthermore, they agree with preclinical in vitro and in vivo studies of Andrographis paniculata and Eleutherococcus senticosus preparations [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Antiviral activity of Eleutherococcus extracts were demonstrated in experimental model systems in which rodents were infected with H1N1 influenza A virus [23][24][25][26], human rhinovirus and respiratory syncytial virus [24].…”

Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress‐ and aging‐related diseases

“…This combination was tested in controlled clinical trials for the treatment of common cold and influenza‐associated uncomplicated upper respiratory infections as well as for the prevention of common colds 421–424 . The studies confirmed the safety and superior efficacy of this combination regimen as compared with monodrug therapy, 425 presumably because of its antiviral effects, 426–432 effects on innate and adaptive immunity, 433–437 and anti‐inflammatory, antioxidant, and detoxifying effects 438–441 of both adaptogenic plants as well as due to their synery 25 . It should be noted that the postmarketing pharmacovigilance assessment of Kan Jang showed a high benefit–risk ratio: one adverse event in about 100,000 patients was recorded for the 23‐year period from the adverse event reports (concerning mainly allergic reactions) to the Swedish and Danish medical product agencies.…”

LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway

“…L antigen family member 3 (LAGE3, NM_006014), a member of the LAGE gene family, is ubiquitously expressed in somatic tissues in humans [9]. LAGE3 is also considered a component of the kinase, endopeptidase and other proteins of small size/endopeptidase-like kinase chromatin-associated protein complex, playing a vital role in the regulation of the positive transcription mediated by RNA polymerase II, tRNA metabolic processing and ncRNA processing [10,11]. The mutation of LAGE3 is linked with nephrotic syndrome associated with primary microcephaly, brain abnormalities and growth retardation [12].…”