Role of MicroRNAs in Protective Effects of Forsythoside A Against Lipopolysaccharide-Induced Inflammation in Bovine Endometrial Stromal Cells

Abstract

Bovine endometrial stromal cells (bESCs) are exposed to a complex environment of bacteria and viruses due to the rupture of epithelial cells after delivery. Inflammatory responses are elicited by the activation of host pattern recognition receptors through pathogen-related molecules such as lipopolysaccharides (LPS) on the cell membrane. Forsythoside A (FTA) is a major active constituent of Forsythia suspensa (Thunb.) Vahl. is a flowering plant widely employed as a traditional Chinese herbal medicine to treat various inflammatory diseases such as nephritis, eye swelling, scabies, ulcers, and mastitis; however, the molecular mechanisms underlying its therapeutic effects on bovine endometritis are still unclear. The aim of this study was to explore the role of miRNA and the mechanisms underlying the protective activity of FTA on the inflammation of bovine endometrial stromal cells induced by LPS. Based on previous research, we isolated and cultured bESCs in vitro and categorized them into LPS and LPS+FTA groups with three replicates. Upon reaching 80% confluence, the bESCs were treated with 0.5 μg/mL of LPS or 0.5 μg/mL of LPS + 100 μg/mL of FTA. We, then, performed high-throughput sequencing (RNA-Seq) to investigate the effects of FTA on LPS-stimulated primary bESCs and their underlying mechanisms. We identified 167 miRNAs differentially expressed in the LPS groups; 72 miRNAs were up-regulated, and 95 were down-regulated. Gene ontology enrichment analysis revealed that differentially expressed microRNA (DEGs) were most enriched during the cellular metabolic process; they were mostly located intracellularly and participated in protein, enzyme, and ion binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were most enriched in the mitogen-activated protein kinase, tumor necrosis factor, and Interleukin-17 signaling pathways. These results reveal the complex molecular mechanism involved in the FTA and provide a basis for future studies of bovine endometritis treatment with traditional Chinese medicine monomer.

Berberine enhances autophagic flux by activating the Nrf2 signaling pathway in bovine endometrial epithelial cells to resist LPS‐induced apoptosis

“…The importance of the epithelial barrier for tolerating pathogens in the uterus is well known (Lv et al, 2021). Many studies have shown that the epithelial barrier is also damaged by LPS through the induction of cell apoptosis (Xie, Hou, et al, 2019).…”

Baogong decoction treats endometritis in mice by regulating uterine microbiota structure and metabolites

“…Traditional Chinese medicine (TCM) has been used to treat endometritis with the advantages of high safety, few side effects and no residual antibiotics (Wei et al, 2017 , Hu et al, 2020b , Lv et al, 2021 ). However, its mechanism needs to be elucidated.…”

Forsythiaside A Ameliorates Sepsis-induced Acute Kidney Injury via Anti-inflammation and Antiapoptotic Effects by Regulating Endoplasmic Reticulum Stress

“…Forsythia is a traditional Chinese medicine, recorded in the Shennong Bencao Jing for the treatment of fever, in ammation, gonorrhea, carbuncle, and erysipelas [15,16]. Modern pharmacology shows that Forsythiaside A (FTA) extracted from Forsythia Fructus has antibacterial [17], antioxidant [18], antiviral [19,20], hepatoprotective [21,22], anti-in ammatory [23,24], neuroprotective [25] and other pharmacological effects. Numerous experimental studies have reported the therapeutic effects of forsythoside A in various models of in ammation.…”