Anti-coronavirus and anti-pulmonary inflammation effects of iridoids, the common component from Chinese herbal medicines for the treatment of COVID-19

• Published in: Journal of natural medicines Vol. 78; no. 4; pp. 1003 - 1012
• Main Authors: Huang, Dan-Yu, Luo, Yong-Xin, Zheng, Wen-De, Wu, Shu-Yu, Huang, Pei-Qi, Jin, Jing-Wei, Wu, Pan-Pan, Gan, Li-She
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.09.2024; Springer Nature B.V
• Subjects: ACE2; Angiotensin-converting enzyme 2; Biomedical and Life Sciences; Biomedicine; Complementary & Alternative Medicine; Coronaviruses; COVID-19; Food industry; Herbal medicine; Hydrogen bonding; Hydrophobicity; Inflammation; Interleukins; Medicinal Chemistry; Medicinal plants; Pharmacology/Toxicology; Pharmacy; Plant Sciences; Severe acute respiratory syndrome coronavirus 2; Tumor necrosis factor-α; Chinese herbal medicine; Iridoids; Anti-coronaviruses; Anti-pulmonary inflammation; Structure–activity relationship
• ISSN: 1340-3443; 1861-0293; 1861-0293
• DOI: 10.1007/s11418-024-01820-3

The practice of Chinese herbal medicines for the treatment of COVID-19 in China played an essential role for the control of mortality rate and reduction of recovery time. The iridoids is one of the main constituents of many heat-clearing and detoxifying Chinese medicines that were largely planted and frequently used in clinical practice. Twenty-three representative high content iridoids from several staple Chinese medicines were obtained and tested by a SARS-CoV-2 pseudo-virus entry-inhibition assay on HEK-293 T/ACE2 cells, a live HCoV-OC43 virus infection assay on HRT-18 cells, and a SARS-CoV-2 3CL protease inhibitory FRET assay followed by molecular docking simulation. The anti-pulmonary inflammation activities were further evaluated on a TNF-α induced inflammation model in A549 cells and preliminary SARs were concluded. The results showed that specnuezhenide ( 7 ), cornuside ( 12 ), neonuezhenide ( 15 ), and picroside III ( 21 ) exhibited promising antiviral activities, and neonuezhenide ( 15 ) could inhibit 3CL protease with an IC 50 of 14.3 μM. Docking computation showed that compound 15 could bind to 3CL protease through a variety of hydrogen bonding and hydrophobic interactions. In the anti-pulmonary inflammation test, cornuside ( 12 ), aucubin ( 16 ), monotropein ( 17 ), and shanzhiside methyl ester ( 18 ) could strongly decrease the content of IL-1β and IL-8 at 10 μM. Compound 17 could also upregulate the expression of the anti-inflammatory cytokine IL-10 significantly. The iridoids exhibited both anti-coronavirus and anti-pulmonary inflammation activities for their significance of existence in Chinese herbal medicines, which also provided a theoretical basis for their potential utilization in the pharmaceutical and food industries. Graphical Abstract