Therapeutic Effect Of The Flower Buds Of Tussilago Farfara L.and Its Effective Ingredient Against Lung Inflammation

The flower buds of Tussilago farfara L.(FTF)is frequently used in the clinical practice to treat lung inflammation-related diseases in traditional Chinese medicine.It contains diverse chemical components including terpenoids,organic acids,flavonoids,alkaloids,and steroids.Lung inflammation-related diseases such as asthma,chronic obstructive pulmonary disease,pulmonary fibrosis,lung inflammation,etc,are accompanied by the presence of oxidative stress and inflammation.Focusing on the flower buds of Tussilago farfara L.and its active ingredient Tussilagone(TUS),this article used mouse model and cell model induced by cigarette smoke(CS)to confirm their effectiveness of intervention in lung inflammation and explored their mechanism of intervention lung inflammation surrounding Nrf2/NF-κB pathway,NLRP3 inflammasome.The research content mainly consists of the following two parts.Part-1 Therapeutic effect of FTF-EtOH against lung inflammationFTF is a frequently prescribed component in plenty of traditional Chinese medicine(TCM)formulas which are used to treat respiratory diseases.In this part of study,the ethanol extract of FTF(FTF-EtOH)showed the effect of inhibiting the overproduction of TNF-α and ROS in vitro.FTF-EtOH reversed the CS-induced lung inflammation in mice and protected the lungs from oxidative stress.The mechanism of FTF-EtOH intervention in lung inflammation was further explored,and the results including the following three parts:(1)FTF-EtOH activated the Nrf2 pathway by promoting the translocation of Nrf2 into the nucleus,inhibiting Nrf2 ubiquitination and enhancing the stability of Nrf2,thereby inhibited CS-induced oxidative stress in the lungs.(2)FTF-EtOH is a broad-spectrum inhibitor of NLRP3 inflammasomes.It inhibited the inflammatory response by inhibiting the activation of NLRP3 inflammasomes and reduced the overproduction of IL-1β and Caspase-1.(3)FTF-EtOH inhibited the NF-κB inflammatory pathway in a dose-dependent manner and reduced the synthesis of downstream inflammatory proteins COX-2 and iNOS.The regulatory effects of the above three pathways have been verified in mice induced by CS.Part 2:Inducing effect of Nrf2 pathway and binding Site of TUSTUS is the main medicinal ingredient of FTF and the quality control component of FTF according to the Chinese Pharmacopoeia.TUS contains an α,β-unsaturated ketone structure,so it has strong electrophilicity,which makes TUS have the potential to bind to the highly active cysteine in Keap-1 protein to change the configuration of Keap-1.In this part of the study,we explored the effect on the Nrf2 pathways and binding sites of TUS,and found the following.(1)TUS dose-dependently induced the protein levels of Nrf2 pathway;(2)TUS promoted the translocation of Nrf2 protein into the nucleus and prolong the half-life of Nrf2,it formed non-covalent interaction with specific amino acid residues in Keap-1 and covalent bond with highly active cysteine,which interfered the connection of Nrf2-Keap-1;(3)TUS increased the level of GSH and suppressed the internal ROS generation induced by CS;(4)TUS also induced the Nrf2 pathway in mice and reversed the inflammatory response in the lung tissue of mice induced by CS.Innovations in this article:(1)FTF is a commonly used medicine for the treatment of respiratory diseases in TCM.This study proved the effectiveness of FTF to intervene in lung inflammation with modern biotechnology;(2)This study reveald the mechanism of FTF-EtOH intervening pulmonary inflammation by exploring the activity of FTF-EtOH,which provided theoretical guidance for further drug development;(3)Drug development requires a clear mechanism and site.This project confirmd the Nrf2 inducing activity of TUS,and furtherly explored the molecular binding sites of TUS.This subject conducted in-depth research on the effectiveness and mechanism of the FTF and its medicinal components TUS in interfering with CS-induced pulmonary inflammation.The results supported the clinical application of FTF,and on the other hand,further development intervention Drugs for inflammatory diseases of the lungs laid the foundation and it laid the foundation for the further development of drugs that interfere with lung inflammatory diseases.