ABSTRACT
Viral respiratory infections are major human health concerns. The most striking epidemic disease, COVID-19 is still on going with the emergence of fast mutations and drug resistance of pathogens. A few polysaccharide macromolecules from traditional Chinese medicine (TCM) have been found to have direct anti-SARS-CoV-2 activity but the mechanism remains unclear. In this study, we evaluated the entry inhibition effect of Lycium barbarum polysaccharides (LBP) in vitro and in vivo. We found LBP effectively suppressed multiple SARS-CoV-2 variants entry and protected K18-hACE2 mice from invasion with Omicron pseudovirus (PsV). Moreover, we found LBP interfered with early entry events during infection in time-of-addition (TOA) assay and SEM observation. Further surface plasmon resonance (SPR) study revealed the dual binding of LBP with Spike protein and ACE2, which resulted in the disruption of Spike-ACE2 interaction and subsequently triggered membrane fusion. Therefore, LBP may act as broad-spectrum inhibitors of virus entry and nasal mucosal protective agent against newly emerging respiratory viruses, especially SARS-CoV-2.
Subject(s)
COVID-19 , Lycium , Humans , Animals , Mice , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Spike Glycoprotein, Coronavirus , Protein BindingABSTRACT
INTRODUCTION: Human potassium chloride cotransporter-1 (KCC1) gene is expressed in endometrial cancer and related to metastasis of endometrial cancer. However, whether KCC1 contributes to invasion and metastasis of endometrial cancer has not been thoroughly investigated. The purpose of this study is to research the alternation effect of insulin-like growth factor I (IGF-I) on the expression of KCC1 in endometrial cancer HEC-1B cells and to explore the mechanism of how KCC1 regulates the invasion ability of HEC-1B cells through the extracellular signal-regulated kinase (ERK) signaling pathway. METHODS: First, the inhibitive effect of RNA interference to KCC1 was detected by semiquantitative reverse transcriptase-polymerase chain reaction. Western blot was used to measure expression changes of KCC1 after exposure to IGF-I in the HEC-1B cells. The change in quantity of phosphorylated ERK1/2 (p-ERK1/2) and cell invasion ability also were measured. After RNA interference and treatment with U0126, the quantity of p-ERK1/2 and the cell invasion ability were measured again. RESULTS: After the application of IGF-I on the HEC-1B cells, the expression of KCC1 and p-ERK1/2 increased dramatically, and the cell invasion ability advanced. RNA interference could inhibit the expression of KCC1, and the quantity of p-ERK1/2 and the cell invasion ability decreased even under the effect of IGF-I. Furthermore, after treatment with U0126, the cell invasion ability no longer advanced even under the effect of IGF-I either. CONCLUSIONS: Insulin-like growth factors I can induce the upregulation of KCC1 gene, and KCC1 gene participates in the invasion ability of HEC-1B cells through the ERK signaling pathway.
Subject(s)
Carcinoma/genetics , Cell Movement/genetics , Endometrial Neoplasms/genetics , MAP Kinase Signaling System/genetics , Symporters/genetics , Butadienes/pharmacology , Carcinoma/pathology , Cell Adhesion/drug effects , Cell Adhesion/genetics , Cell Line, Tumor , Cell Movement/drug effects , Drug Evaluation, Preclinical , Endometrial Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Insulin-Like Growth Factor I/pharmacology , MAP Kinase Kinase 1/antagonists & inhibitors , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , Neoplasm Invasiveness , Nitriles/pharmacology , Protein Kinase Inhibitors/pharmacology , Up-Regulation/drug effects , Up-Regulation/genetics , K Cl- CotransportersABSTRACT
OBJECTIVE: To analyze the correlation between the quality of Cornus officinalis and the contents of the inorganic elements in the planting soil. METHODS: The contents of 11 kinds of inorganic elements including Zn, Mn, K, Fe, Mg, Ca, Cu, Cd, As, Pb and Hg in Cornus officinalis and the planting soil were determined; The contents of loganin, ursolic acid, polysaccharides, tannins, organic acid, water-soluble extractives and ethanol-soluble extractives in Cornus officinalis were determined; The correlation between the quality of Cornus officinalis and the contents of the inorganic elements in the planting soil was analyzed. RESULTS: There was no significant difference in the content of chemical components of Cornus officinalis produced in the three main areas. The contents of loganin and water-soluble extract complied with pharmacopoeial provisions. Especially, inorganic elements of Fe, Mn and K had significant effects on the quality of Cornus officinalis. CONCLUSION: The results provide the foundation for the selection of cultivating area and the reference for standard cultivation of Cornus officinalis.