Kaempferol has potential anti‐coronavirus disease 2019 (COVID‐19) targets based on bioinformatics analyses and pharmacological effects on endotoxin‐induced cytokine storm

Abstract

COVID‐19 has infected 272 million patients and caused 5.33 million deaths around the world, and it remains the main global threat. Previous studies revealed that Chinese traditional medicine is an effective treatment for COVID‐19 infection. This study aims to reveal the pharmacological effects of kaempferol, which is the active component of Radix Bupleuri and Tripterygii Radix, and potential mechanisms for the treatment of COVID‐19. Here, we employed the bioinformatics methods to filter the anti‐COVID‐19 candidate genes of kaempferol, which mainly enriched in inflammation (TNF, JUN, etc.) and virus infection (AKT1, JNK, etc.). The Transcription levels of AKT1, JNK and JUN were significantly reduced by kaempferol treatment in the LPS‐activated macrophages. In addition, kaempferol reduced the secretion of inflammatory factors by LPS‐stimulated macrophages, inhibited MAPK/NF‐κB signaling and regulated macrophage polarization to M2 type in vitro, and suppressed endotoxin‐induced cytokine storm and improved survival in mice. Molecular docking analysis demonstrated that kaempferol was probable to bind the COVID‐19 protein 5R84 and formatted hydrogen bond with the residues, the free binding energy of which was lower than the original ligand. In summary, our current work indicates that kaempferol has anti‐COVID‐19 potential through the reduction of COVID‐19‐induced body dysfunction and molecule–protein interaction, and bioinformatics results clarify that some of these key target genes might serve as potential molecular markers for detecting COVID‐19.

Flavonoids derived from medicinal plants as a COVID‐19 treatment

“…Kaempferol may play an important role in the prevention and treatment of COVID-19, according to studies (Khalil et al, 2020;Sun et al, 2023). It has been reported that the traditional Chinese herbal Abbreviations: 3CL pro , 3-chymotrypsin-like protease; ACE2, angiotensin-converting enzyme 2; M pro , main proteinase; NSPs, nonstructural proteins; PLpro, papain-like protease; RdRp, RNA-dependent RNA polymerase; S-Protein, spike protein; TMPRSS2, transmembrane serine protease 2.…”

“…Molecular docking analysis revealed that kaempferol can bind the SARS-CoV-2 protein 5R84 and form a hydrogen bond with the residues, whose free binding energy is less than that of the original ligand (Sun et al, 2023).…”

“…Anticancer, antimicrobial, neuroprotective, antioxidant, antiallergic, and cardioprotective properties have been reported (Singhal et al, 2021). Kaempferol may play an important role in the prevention and treatment of COVID‐19, according to studies (Khalil et al, 2020; Sun et al, 2023). It has been reported that the traditional Chinese herbal remedy Lianhua Qingwen contains essential components such as KAE, which demonstrate a high binding affinity with 3CL pro of SARS‐CoV‐2, and that these components may modulate the inflammatory response of patients with severe COVID‐19 (Shen & Yin, 2021).…”

“…It has been reported that the traditional Chinese herbal remedy Lianhua Qingwen contains essential components such as KAE, which demonstrate a high binding affinity with 3CL pro of SARS‐CoV‐2, and that these components may modulate the inflammatory response of patients with severe COVID‐19 (Shen & Yin, 2021). Sun et al (2023) have recently discovered, through bioinformatics analysis and pharmacological effects on endotoxin‐induced cytokine storms, that KAE offers potential targets for combating COVID‐19. In their study, they confirmed that kaempferol suppresses the activation of the MAPK/NF‐B pathway in LPS‐stimulated macrophages and inhibits the secretion of inflammatory factors; they also demonstrated that kaempferol inhibits endotoxin‐induced cytokine storm, thereby ameliorating inflammatory pathology and enhancing mouse survival.…”

“…In their study, they confirmed that kaempferol suppresses the activation of the MAPK/NF‐B pathway in LPS‐stimulated macrophages and inhibits the secretion of inflammatory factors; they also demonstrated that kaempferol inhibits endotoxin‐induced cytokine storm, thereby ameliorating inflammatory pathology and enhancing mouse survival. Molecular docking analysis revealed that kaempferol can bind the SARS‐CoV‐2 protein 5R84 and form a hydrogen bond with the residues, whose free binding energy is less than that of the original ligand (Sun et al, 2023).…”