Chemical characterization of Jing Guan Fang and its application in alleviating coronavirus envelope protein-induced proinflammatory responses in vitro and in vivo

Background and aim Jing Guan Fang (JGF) is an herbal formulation developed for the prevention of COVID-19 via SARS-CoV-2 infection. In this study, we aimed to clarify the anti-inflammatory effects of JGF on macrophages stimulated by the SARS-CoV-2 envelope protein (2-E) both in vitro and in vivo. Experimental procedure In vitro , typical and alveolar macrophages were treated with JGF under 2-E stimulation to evaluate changes in inflammatory mediators and signaling pathways. A mouse model using murine macrophages was also employed to assess JGF's anti-inflammatory effects. Mice received oral JGF administration, and the inflammatory responses induced by the 2-E protein were examined in bronchoalveolar lavage fluid and blood serum. Results and conclusions The mouse model showed oral JGF administration could sufficiently reduce 2-E-stimulated proinflammatory factors in the bronchoalveolar lavage and blood serum. Moreover, JGF suppressed the 2-E-induced NO, TNF-α, and IL-6 production as well as the expression of iNOS and COX-2 in murine typical and alveolar macrophages. Mechanistically, JGF attenuated 2-E-mediated phosphorylation of STAT3 and ERK1/2 signaling pathways. Furthermore, baicalin and wogonoside, key components of JGF, demonstrated potent efficacy. To our knowledge, this is the first study to show that JGF mitigates 2-E-induced proinflammatory responses via modulation of STAT3 and ERK signaling, supporting its potential as a therapeutic herbal formulation against coronavirus E protein-related cytokine storms.