Jubang Huashi Yin and its active component cynaroside alleviate excessive inflammation in COVID-19 by inhibiting IKKβ activity

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, triggering a series of immune responses such as cytokine storms. Traditional Chinese medicine (TCM) has demonstrated notable efficacy in COVID-19 treatment. However, their mechanisms of action remain largely elusive. In this study, by reversing dysregulated signaling pathways in cells in the context of COVID-19, Jubang Huashi Yin (JBHSY) was developed based on the transcriptome of TCM-treated macrophages and lung epithelial cells. We identified 16 compounds in JBHSY through fingerprint analysis and found that JBHSY alleviated lung inflammation in SARS-CoV-2-infected human angiotensin-converting enzyme 2 (hACE2) transgenic mice and downregulated cytokine expression by suppressing the activity of an inhibitor of κB kinase β (IKKβ) in vitro. In addition, in vitro screening experiments revealed that Chrysanthemi Indici Flos (CIF) is an essential anti-inflammatory herb in JBHSY. Moreover, molecular docking experiments revealed cynaroside to be an active component in CIF that regulates IKKβ. Additionally, an in vitro screening assay indicated that 12 prototype compounds, including cyanidin 3-glucoside from CIF and licoflavone A from Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, in rat serum after JBHSY administration possessed antiviral potential. Given its anti-inflammatory potential, JBHSY is recommended for COVID-19 treatment.