Oxidative stress,inflammatory,and excessive apoptosis are the crucial culprits of drug-induced liver injury(DILI).Torularhodin was judged to have good potential to intervene DILI due to its antioxidant and immunomodulation activity.The aim of this study was to clarify the preventive effect of torularhodin on hepatic injury caused by acetaminophen(APAP)and its mechanism in mice.The liver injury model of mice was established by injecting APAP into the tail’s veins to evaluate the intervention effect of torularhodin on liver injury.The mechanisms involved were investigated using Western blot and transcriptome analysis.The results reflected that torularhodin significantly increased antioxidant enzyme capacities(Compared with the group Dam,the activities of SOD and GSH-Px in the group TorH increased by2.47 and 3.79 times,and the content of MDA decreased by 58.78%,respectively p<0.05),alleviated inflammation(Compared with the group Dam,the contents of TNF-α,IL-1β and IL-6 in the group TorH increased by 61.98%,64.93%and 58.49,respectively,p<0.05)and improved the pathological condition of liver in mice.Transcriptomic result indicated that differential genes caused by the intervention of torularhodin were mainly involved in cell metabolism processes,immunomodulation and apoptosis.Western blot results confirmed that torularhodin could inhibit hepatocyte apoptosis by regulating signaling pathways including PI3K/Akt/mTOR and Nrf2/HO-1 to increase antioxidant enzyme activity,thus intervening in DILI.It suggested that torularhodin might provide a promising preventive strategy for DILI.
Objective:Identifying novel strategies to prevent particulate matter(PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases.The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention.The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs(MECHs)formula against PM-induced lung injury.Methods:PM-induced oxidative stress,inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant,anti-inflammatory and anti-apoptotic MECHs,respectively.A network pharmacology method was utilized to rationally design a novel herbal formula.Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula.The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish.The MECH formula against PM-induced lung injury was investigated with mice experiments.Results:Five selected herbs were rationally designed to form a new MECH formula,including Citri Exocarpium Rubrum(Juhong),Lablab Semen Album(Baibiandou),Atractylodis Macrocephalae Rhizoma(Baizhu),Mori Folium(Sangye)and Polygonati Odorati Rhizoma(Yuzhu).The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish.The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px,reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine(IL-6,IL-8,IL-1βand TNFa),down regulating the protein expression of NF-κB,STAT3 and Caspase-3.Conclusion:Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.
