RESUMO
Stress diarrhea is a major challenge for weaned piglets and restricts pig production efficiency and incurs massive economic losses. A traditional Chinese medicine prescription (QJC) composed of Astragalus propinquus Schischkin (HQ), Zingiber officinale Roscoe (SJ), and Plantago asiatica L. (CQC) has been developed by our laboratory and shows marked anti-stress diarrhea effect. However, the active compounds, potential targets, and mechanism of this effect remain unclear and warrant further investigation. In our study, we verified the bioactive compounds of QJC and relevant mechanisms underlying the anti-stress diarrhea effect through network pharmacology and in vivo experimental studies. After establishing a successful stress-induced diarrhea model, histomorphology of intestinal mucosa was studied, and Quantitative real-time PCR (RT-qPCR) probe was used for the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway to verify the therapeutic effect of QJC on diarrhea. First, using the network pharmacology approach, we identified 35 active components and 130 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in QJC. From among these, we speculated that quercetin, luteolin, kaempferol, scutellarein, and stigmasterol were the main bioactive compounds and assumed that the anti-diarrhea effect of QJC was related to the PI3K-Akt signaling pathway. The RT-qPCR indicated that QJC and its bioactive components increased the expression levels of PI3K and Akt, inhibited the expression of phosphatase and tensin homolog (PTEN), and activated the PI3K-Akt signaling pathway to relieve stress-induced diarrhea. Furthermore, we found that QJC alleviated the pathological condition of small intestine tissue and improved the integrity of the intestinal barrier. Taken together, our study showed that the traditional Chinese medicine QJC, quercetin, luteolin, kaempferol, scutellarein, and stigmasterol alleviated the pathological condition of small intestine tissue and relieved stress-induced diarrhea by increasing the expression levels of PI3K and Akt and inhibiting the expression levels of PTEN.
RESUMO
Bioactive compounds from Traditional Chinese Medicines (TCMs) are gradually becoming an effective alternative in the control of porcine reproductive and respiratory syndrome virus (PRRSV) because most of the commercially available PRRSV vaccines cannot provide full protection against the genetically diverse strains isolated from farms. Besides, the incomplete attenuation procedure involved in the production of modified live vaccines (MLV) may cause them to revert to the more virulence forms. TCMs have shown some promising potentials in bridging this gap. Several investigations have revealed that herbal extracts from TCMs contain molecules with significant antiviral activities against the various stages of the life cycle of PRRSV, and they do this through different mechanisms. They either block PRRSV attachment and entry into cells or inhibits the replication of viral RNA or viral particles assembly and release or act as immunomodulators and pathogenic pathway inhibitors through cytokines regulations. Here, we summarized the various antiviral strategies employed by some TCMs against the different stages of the life cycle of PRRSV under two major classes, including direct-acting antivirals (DAAs) and indirect-acting antivirals (IAAs). We highlighted their mechanisms of action. In conclusion, we recommended that in making plans for the use of TCMs to control PRRSV, the pathway forward must be built on a real understanding of the mechanisms by which bioactive compounds exert their effects. This will provide a template that will guide the focus of collaborative studies among researchers in the areas of bioinformatics, chemistry, and proteomics. Furthermore, available data and procedures to support the efficacy, safety, and quality control levels of TCMs should be well documented without any breach of data integrity and good manufacturing practices.