C3H Expression Is Crucial for Methyl Jasmonate Induction of Chicoric Acid Production by Echinacea purpurea (L.) Moench Cell Suspension Cultures.

Echinacea purpurea (L.) Moench is one of the most economically important medicinal plants, cultivated worldwide for its high medicinal value and with several industrial applications in both pharmaceutical and food industries. Thanks to its various phytochemical contents, including caffeic acid derivatives (CADs), E. purpurea extracts have antioxidant, anti-inflammatory, and immuno-stimulating properties. Among CADs, chicoric acid is one of the most important compounds which have shown important pharmacological properties. The present research was aimed at optimizing the production of chicoric acid in E. purpurea cell culture. Methyl jasmonate (MeJa) at different concentrations and for different duration of treatments was utilized as elicitor, and the content of total polyphenols and chicoric acid was measured. Several genes involved in the chicoric acid biosynthetic pathway were selected, and their expression evaluated at different time points of cell culture growth. This was performed with the aim of identifying the most suitable putative molecular markers to be used as a proxy for the early prediction of chicoric acid contents, without the need of expensive quantification methods. A correlation between the production of chicoric acid in response to MeJa and an increased response to oxidative stress was also proposed.

Rational and Safe Use of the Top Two Botanical Dietary Supplements to Enhance the Immune System.

The recent COVID-19 pandemic has sparked great interest in strengthening the immune system, especially by the consumption of widely available natural dietary supplements. Because of this popularity, it was suggested that the sales of these products would grow significantly in the year 2021, especially for those who are unable or unwilling to receive COVID-19 vaccines. Among the many botanicals, Sambucus nigra L. (Elderberry) and Echinacea purpurea (L.) Moench (Echinacea) have especially shown great popularity. Various in vivo and in vitro tests of S. nigra and E. purpurea extracts and constituents have confirmed the botanicals' influence on proinflammatory cytokines, viral infections, and flu symptoms, proving their immunomodulatory and antiviral effects. Although there have been promising results with S. nigra and E. purpurea containing supplements, thorough monitoring of the sanitary production, demand, and related side effects after consumption is required. Further research and development of the supplements in accordance with the pandemic are also advised.

Echinacea purpurea (L.) Moench treatment of monocytes promotes tonic interferon signaling, increased innate immunity gene expression and DNA repeat hypermethylated silencing of endogenous retroviral sequences.

BACKGROUND: Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections. METHODS: Transcriptome, epigenome and kinome profiling allowed a systems biology level characterisation of genomewide immunomodulatory effects of a standardized Echinacea purpurea (L.) Moench extract in THP1 monocytes. RESULTS: Gene expression and DNA methylation analysis revealed that Echinaforce® treatment triggers antiviral innate immunity pathways, involving tonic IFN signaling, activation of pattern recognition receptors, chemotaxis and immunometabolism. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi) genomic protective response against viral infections. CONCLUSIONS: Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity through tonic IFN regulation of pattern recognition and chemokine gene expression and DNA repeat hypermethylated silencing of HERVs in monocytes. These results suggest that immunomodulation by Echinaforce® treatment holds promise to reduce symptoms and duration of infection episodes of common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2, with strongly impaired interferon (IFN) response and weak innate antiviral defense.

The effects of combination of Zingiber officinale and Echinacea on alleviation of clinical symptoms and hospitalization rate of suspected COVID-19 outpatients: a randomized controlled trial.

OBJECTIVES: Herbal medicines, as a treatment method, have received a great deal of attention. The effects of two herbal medicines namely Zingiber officinale and Echinacea on alleviation of clinical symptoms and hospitalization rate of suspected COVID-19 outpatients were examined. METHODS: A clinical trial with 100 suspected COVID-19 outpatients as participants was conducted. The participants were allocated randomly to two groups of 50 members. The intervention group received concurrent Zingiber officinale (Tablet Vomigone 500 mg II tds) and Echinacea (Tablet Rucoldup I tds) for seven days in addition to the standard treatment. The control group only received the standard treatment (Hydroxychloroquine). After seven days, alleviation of clinical symptoms and hospitalization rate were examined. In addition, 14 days after treatment, the hospitalization was assessed again by telephone follow up. RESULTS: The two groups were identical in terms of basic characteristics. Improvement level as to coughing, dyspnea, and muscle pain was higher in the intervention group (p value <0.05). There was no significant difference between the two groups in terms of the other symptoms. In addition, the hospitalization rate in the intervention and control groups were 2 and 6% respectively, which are not significantly different (p value >0.05). CONCLUSIONS: Taking into account the efficiency and trivial side-effects of Zingiber officinale and Echinacea, using them for alleviation and control of the clinical symptoms in COVID-19 outpatients is recommended.

Structure-Based Identification of Natural Products as SARS-CoV-2 Mpro Antagonist from Echinacea angustifolia Using Computational Approaches.

Coronavirus disease-19 (COVID-19) pandemic, caused by the novel SARS-CoV-2 virus, continues to be a global threat. The number of cases and deaths will remain escalating due to the lack of effective therapeutic agents. Several studies have established the importance of the viral main protease (Mpro) in the replication of SARS-CoV-2 which makes it an attractive target for antiviral drug development, including pharmaceutical repurposing and other medicinal chemistry approaches. Identification of natural products with considerable inhibitory potential against SARS-CoV-2 could be beneficial as a rapid and potent alternative with drug-likeness by comparison to de novo antiviral drug discovery approaches. Thereof, we carried out the structure-based screening of natural products from Echinacea-angustifolia, commonly used to prevent cold and other microbial respiratory infections, targeting SARS-CoV-2 Mpro. Four natural products namely, Echinacoside, Quercetagetin 7-glucoside, Levan N, Inulin from chicory, and 1,3-Dicaffeoylquinic acid, revealed significant docking energy (>-10 kcal/mol) in the SARS-CoV-2 Mpro catalytic pocket via substantial intermolecular contacts formation against co-crystallized ligand (<-4 kcal/mol). Furthermore, the docked poses of SARS-CoV-2 Mpro with selected natural products showed conformational stability through molecular dynamics. Exploring the end-point net binding energy exhibited substantial contribution of Coulomb and van der Waals interactions to the stability of respective docked conformations. These results advocated the natural products from Echinacea angustifolia for further experimental studies with an elevated probability to discover the potent SARS-CoV-2 Mpro antagonist with higher affinity and drug-likeness.