Towards the end of 2019, an atypical acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China and subsequently named Coronavirus disease 2019 (COVID-19). The rapid dissemination of COVID-19 has provoked a global crisis in public health. COVID-19 has been reported to cause sepsis, severe infections in the respiratory tract, multiple organ failure, and pulmonary fibrosis, all of which might induce mortality. Although several vaccines for COVID-19 are currently being administered worldwide, the COVID-19 pandemic is not yet effectively under control.Therefore, novel therapeutic agents to eradicate the cause of the disease and/or manage the clinical symptoms of COVID-19 should be developed to effectively regulate the current pandemic. In this review, we discuss the possibility of managing the clinical symptoms of COVID-19 using natural products derived from medicinal plants used for controlling pulmonary inflammatory diseases in folk medicine. Diverse natural products have been reported to exert potential antiviral effects in vitro by affecting viral replication, entry into host cells, assembly in host cells, and release. However, the in vivo antiviral effects and clinical antiviral efficacies of these natural products against SARS-CoV-2 have not been successfully proven to date. Thus, these properties need to be elucidated through further investigations, including randomized clinical trials, in order to develop optimal and ideal therapeutic candidates for COVID-19.

In this study, we investigated whether eriodictyol exerts an effect on the production and gene expression of MUC5AC mucin in human pulmonary epithelial NCI-H292 cells. The cells were pretreated with eriodictyol for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. The effect of eriodictyol on PMA-induced nuclear factor kappa B (NF-κB) signaling pathway was also investigated. Eriodictyol suppressed the MUC5AC mucin production and gene expression induced by PMA via suppression of inhibitory kappa Bα degradation and NF-κB p65 nuclear translocation. These results suggest that eriodictyol inhibits mucin gene expression and production in human airway epithelial cells via regulation of the NF-κB signaling pathway.

Multinucleated cells resulted from mitosis defect have been noted in pathophysiological states of the cells such as inflammation, senescence and cancer. Since oxidative stress has been known to correlate with these pathophysiological conditions, we tested the effect of H2O2 on the cell cycle progression and formation of multinucleated cells. H2O2 induced a significant delay in cell cycle progression in Chang liver cells. Interestingly, H2O2 actively induced hyperamplification of centrosomes (> or =3) and multipolar spindle formation during mitosis and subsequently increased the generation of multinucleated cells. A significant increase of the phospho-ERK level was observed upon H2O2 treatment but PD98059, an MEK1/2 inhibitor, didn't reduce the frequency of cells with hyperamplified centrosomes. On the other hand, treatment of either H2O2 or adriamycin increased intracellular ROS levels and multinucleated cells, which were significantly suppressed by antioxidants, N-acetylcysteine and PDTC. Thus, our results suggest that oxidative stress can trigger centrosome hyperamplification and multinucleated cell formation, which may promote pathophysiological progression.
Cell Line ; Cell Nucleus/*drug effects/*metabolism ; Centrosome/*drug effects/*metabolism ; Gene Amplification ; Humans ; Hydrogen Peroxide/*pharmacology ; MAP Kinase Signaling System ; Mitotic Spindle Apparatus/drug effects ; Phenotype ; Reactive Oxygen Species/metabolism ; Research Support, Non-U.S. Gov't

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver, and there is a global increase in its incidence owing to changes in lifestyle and diet. Recent findings suggest that p53 is involved in the development of non-alcoholic fatty liver disease; however, the association between p53 expression and the disease remains unclear. Doxorubicin, an anticancer agent, increases the expression of p53. Therefore, this study aimed to investigate the role of doxorubicin-induced p53 upregulation in free fatty acid (FFA)-induced intracellular lipid accumulation. HepG2 cells were pretreated with 0.5 μg/mL of doxorubicin for 12 h, followed by treatment with FFA (0.5 mM) for 24 h to induce steatosis. Doxorubicin pretreatment upregulated p53 expression and downregulated the expression of endoplasmic reticulum stress- and lipid synthesis-associated genes in the FFA -treated HepG2 cells. Additionally, doxorubicin treatment upregulated the expression of AMP-activated protein kinase, a key modulator of lipid metabolism. Notably, siRNA-targeted p53 knockdown reversed the effects of doxorubicin in HepG2 cells.Moreover, doxorubicin treatment suppressed FFA -induced lipid accumulation in HepG2 spheroids. Conclusively, these results suggest that doxorubicin possesses potential application for the regulation of lipid metabolism by enhance the expression of p53 an in vitro NAFLD model.