Aesculus hippocastanum extract and the main bioactive constituent ß-escin as antivirals agents against coronaviruses, including SARS-CoV-2.

Respiratory viruses can cause life-threatening illnesses. The focus of treatment is on supportive therapies and direct antivirals. However, antivirals may cause resistance by exerting selective pressure. Modulating the host response has emerged as a viable therapeutic approach for treating respiratory infections. Additionally, considering the probable future respiratory virus outbreaks emphasizes the need for broad-spectrum therapies to be prepared for the next pandemics. One of the principal bioactive constituents found in the seed extract of Aesculus hippocastanum L. (AH) is ß-escin. The clinical therapeutic role of ß-escin and AH has been associated with their anti-inflammatory effects. Regarding their mechanism of action, we and others have shown that ß-escin and AH affect NF-κB signaling. Furthermore, we have reported the virucidal and broad-spectrum antiviral properties of ß-escin and AH against enveloped viruses such as RSV, in vitro and in vivo. In this study, we demonstrate that ß-escin and AH have antiviral and virucidal activities against SARS-CoV-2 and CCoV, revealing broad-spectrum antiviral activity against coronaviruses. Likewise, they exhibited NF-κB and cytokine modulating activities in epithelial and macrophage cell lines infected with coronaviruses in vitro. Hence, ß-escin and AH are promising broad-spectrum antiviral, immunomodulatory, and virucidal drugs against coronaviruses and respiratory viruses, including SARS-CoV-2.

The Flavonoid Cyanidin Shows Immunomodulatory and Broad-Spectrum Antiviral Properties, Including SARS-CoV-2.

New antiviral treatments are needed to deal with the unpredictable emergence of viruses. Furthermore, vaccines and antivirals are only available for just a few viral infections, and antiviral drug resistance is an increasing concern. Cyanidin (a natural product also called A18), a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, through its anti-inflammatory effects. Regarding its mechanism of action, A18 was identified as an IL-17A inhibitor, resulting in the attenuation of IL-17A signaling and associated diseases in mice. Importantly, A18 also inhibits the NF-κB signaling pathway in different cell types and conditions in vitro and in vivo. In this study, we report that A18 restricts RSV, HSV-1, canine coronavirus, and SARS-CoV-2 multiplication, indicating a broad-spectrum antiviral activity. We also found that A18 can control cytokine and NF-κB induction in RSV-infected cells independently of its antiviral activity. Furthermore, in mice infected with RSV, A18 not only significantly reduces viral titers in the lungs, but also diminishes lung injury. Thus, these results provide evidence that A18 could be used as a broad-spectrum antiviral and may contribute to the development of novel therapeutic targets to control these viral infections and pathogenesis.

Imiquimod suppresses respiratory syncytial virus (RSV) replication via PKA pathway and reduces RSV induced-inflammation and viral load in mice lungs.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease and bronchiolitis in children, as well as an important cause of morbidity and mortality in elderly and immunocompromised individuals. However, there is no safe and efficacious RSV vaccine or antiviral treatment. Toll Like Receptors (TLR) are important molecular mediators linking innate and adaptive immunity, and their stimulation by cognate agonists has been explored as antiviral agents. Imiquimod is known as a TLR7 agonist, but additionally acts as an antagonist for adenosine receptors. In this study, we demonstrate that imiquimod, but not resiquimod, has direct anti-RSV activity via PKA pathway in HEp-2 and A549 cells, independently of an innate response. Imiquimod restricts RSV infection after viral entry into the host cell, interfering with viral RNA and protein synthesis. Probably as a consequence of these anti-RSV properties, imiquimod displays cytokine modulating activity in RSV infected epithelial cells. Moreover, in a murine model of RSV infection, imiquimod treatment improves the course of acute disease, evidenced by decreased weight loss, reduced RSV lung titers, and attenuated airway inflammation. Consequently, imiquimod represents a promising therapeutic alternative against RSV infection and may inform the development of novel therapeutic targets to control RSV pathogenesis.

Considerações acerca de representações de práticas corporais nas obras confucianas Registro dos ritos e Discursos / Considerations on the social representations of physical practices in the confucian works Discourses and Book of Rites / Consideraciones sobre las representaciones de las prácticas corporales en las obras confucianas Libro de los ritos y Discursos

Resumo Em meio às obras que tomam parte no corpo de conhecimentos produzido pelo confucionismo figuram o Registro dos ritos (Liji) e Discursos (Zhonglun). No presente estudo, buscamos investigar como manifestações da cultura corporal são apresentadas nas referidas obras e o que tais formas de atividades poderiam representar frente ao processo formativo de um indivíduo no contexto de produção desses escritos, conforme o prisma confuciano. Foram identificadas como relevantes para essa discussão informações a respeito da prática de arquearia, presentes no Registro dos ritos, assim como o conceito das Seis Artes, presente na obra Discursos.

Abstract Among the writings that constitute the body of knowledge produced by the Confucianism, one can mention the "Book of Rites" (Liji) and "Discourses" (Zhonglun). In this study, we aim to investigate how these books portray physical culture manifestations and what such type of activities could represent to the formative process of an individual, accordingly with the confucian approach, in the context in which these works were first written. We have considered as relevant issues for this discussion the information regarding the practice of archery included in the Book of Rites, as well as the concept of the "Six Arts", included in the Discourses.

Resumen Entre las obras que forman parte del conjunto de conocimientos producido por el confucianismo se encuentran el Libro de los ritos (Liji) y Discursos (Zhonglun). En el presente estudio queremos investigar cómo las manifestaciones de la cultura corporal se presentan en estas obras y lo que podrían representar estas formas de actividades en el proceso formativo de un individuo en el contexto en que se escribieron estas obras, conforme al prisma confuciano. Se identificaron como relevantes para esa discusión informaciones acerca de la práctica del tiro con arco, presente en el Libro de los ritos, así como el concepto de las «seis artes¼, presente en la obra Discursos.

Aesculus hippocastanum L. seed extract shows virucidal and antiviral activities against respiratory syncytial virus (RSV) and reduces lung inflammation in vivo.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease and bronchiolitis in children worldwide. No vaccine or specific, effective treatment is currently available. ß-escin is one of the main bioactive constituents of Aesculus hippocastanum L. (Hippocastanaceae) seed extract (AH), and both ß-escin and AH have demonstrated a beneficial role in clinical therapy because of their anti-edematous, anti-inflammatory and antioxidative effects. Besides, we have reported that ß-escin and AH show virucidal, antiviral and immunomodulatory activities against the enveloped viruses HSV-1, VSV and Dengue virus in vitro. In this study, we demonstrate that ß-escin and AH have virucidal and antiviral activities against RSV, as well as NF-κB, AP-1 and cytokine modulating activities in RSV infected epithelial and macrophage cell lines in vitro. Besides, in a murine model of pulmonary RSV infection, AH treatment improves the course of acute disease, evidenced by decreased weight loss, reduced RSV lung titers, and attenuated airway inflammation. In contrast, even though ß-escin showed, similarly to AH, antiviral and immunomodulatory properties in vitro, it neither reduces viral titers nor attenuates lung injury in vivo. Thus, our data demonstrate that AH restrains RSV disease through antiviral and immunomodulatory effect.

Natural and semisynthetic diterpenoids with antiviral and immunomodulatory activities block the ERK signaling pathway.

The pathogenesis of many viral infections lies on the damage caused by the immune response against the virus. Current antiviral drugs do not act on the inflammatory component of the disease. Thus, new compounds that inhibit both viral multiplication and the immunopathology elicited by the virus are an approach that should be considered. In the present study, we identified two jatropholones (2A and 5B) and one carnosic acid derivative (9C) that significantly inhibited multiplication of TK+ and TK- strains of HSV-1 in Vero cells. Compounds 2A, 5B and 9C also prevented HSV-1- and TLRs-induced inflammatory response in cultivated murine macrophages. In macrophages infected with HSV-1, the inhibitory effect of compounds 2A, 5B and 9C on TNF-α and IL-6 production could be associated with the block of ERK pathway, whereas NF-κB pathway was not hampered by any of the compounds. Besides, 2A, 5B and 9C also inhibited ERK pathway and reduced TNF-α production in macrophages stimulated with TLR2, TLR4 or TLR9 agonists and were able to hinder IL-6 secretion after activation with TLR2 or TLR4, but not with TLR9. The immunomodulatory effect of 2A, 5B and 9C in macrophages infected with HSV-1 may be a consequence of the inhibition of ERK pathway activated by TLRs. The availability of compounds with both antiviral and immunomodulatory properties which affect TLR signaling pathways might be a useful strategy to control the progress of virus-induced disease.

Representación gráfica octagonal de las curvas volumen - tiempo y flujo - volumen / Octagonal graphic representation of volume - time and flow - curves

Se estudiaron 202 personas, entre sujetos normales y pacientes, desde el punto de vista espirométrico, a los cuales se les realizaron las curvas de Volumen-Tiempo y Flujo - Volumen. De cada prueba se seleccionaron 3 índices y una relación, cuyos resultados se trasladaron luego a una gráfica circular previamente diseñada, permitiendo de esta forma su análisis en conjunto de acuerdo a la configuración octagonal que presentan. El análisis de los resultados espirométricos de esta forma, permite visualmente, tener una idea del comportamiento de cada índice o relación con respecto a los demás, independiente de sus valores numéricos; así como también un diagnóstico más fácil según la forma del octágono de represente. El presente trabajo muestra las gráficas obtenidas para los 4 grupos en que se dividieron los sujetos de investigación y presenta también a discusión una nueva relación entre un índice de la curva de Volumen-Tiempo, Velocidad de Flujo Espiratorio Medio Máximo (VFEMM) y un índice de la curva de Flujo-Volumen, el Flujo Espiratorio Máximo (FEM), VFEMM/FEM, la cual se insinúa de utilidad en el diagnóstico de la enfermedad obstructiva