Chrysosplenol D protects mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via TLR4-MAPKs/NF-κB signaling pathways

Abstract

This study investigated the effect and mechanism of chrysosplenol D (CD) on LPS-induced acute lung injury in mice. Histological changes in the lungs were measured by hematoxylin-eosin staining. The levels of IL-6, IL-1β, and TNF-α in the bronchoalveolar lavage fluid were detected by ELISA. The levels of oxidative stress were detected by the cuvette assay. Immune cells in peripheral blood, the levels of reactive oxygen species, and apoptosis of primary lung cells were detected by flow cytometry. The mRNA levels of TLR4, MyD88, IL-1β, and NLRP3 were measured by quantitative real-time polymerase chain reaction. The levels of proteins in apoptosis and the TLR4-MAPKs/NF-κB signaling pathways were detected by Western blot. Hematoxylin-eosin staining showed that CD could improve lung injury; decrease the levels of inflammatory factors, oxidative stress, reactive oxygen species, and cell apoptosis; and regulate the immune system. Moreover, CD could down-regulate the mRNA levels of TLR4, MyD88, NLRP3, and IL-1β in lung, and the protein levels of Keap-1, Cleaved-Caspase-3/Caspase-3, Cleaved-Caspase-9/Caspase-9, TLR4, MyD88, p-ERK/ERK, p-JNK/JNK, p-p38/p38, p-p65/p65, NLRP3, and IL-1β, and up-regulated the levels of Bcl-2/Bax, p-Nrf2/Nrf2, and HO-1. The results suggested that CD could protect mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via the TLR4-MAPKs/NF-κB signaling pathways.

Downregulation of ROR2 attenuates LPS‐induced A549 cell injury through JNK and ERK signaling pathways

“…It is acknowledged that JNK and ERK1/2 are important proteins in regulating inflammatory responses and cell apoptosis. 28 , 29 , 30 To preliminarily elucidate the mechanism that ROR2 downregulation alleviates inflammatory responses, cell cycle arrest, and cell apoptosis, we examined the JNK and ERK signaling transduction pathways. Western blot results showed that the phosphorylation levels of JNK and ERK1/2 were significantly decreased by downregulating ROR2 in comparison with LPS treatment, suggesting that ROR2 downregulation inhibits JNK and ERK signal pathway.…”

“…It is acknowledged that JNK and ERK1/2 are important proteins in regulating inflammatory responses and cell apoptosis 28–30 . To preliminarily elucidate the mechanism that ROR2 downregulation alleviates inflammatory responses, cell cycle arrest, and cell apoptosis, we examined the JNK and ERK signaling transduction pathways.…”

Epimedium sagittatum Maxim ameliorates adriamycin‐induced nephropathy by restraining inflammation and apoptosis via the PI3K/AKT signaling pathway

“…Studies have revealed that exposure to adriamycin in rats can lead to excessive ROS and cause oxidative stress in the kidney 32 . SOD and GSH‐Px can effectively remove ROS and terminate the free radical reaction, and MDA can reflect the degree of peroxidation damage 33 . In addition, it has been reported that the PI3K/AKT pathway can activate the Nrf2 pathway, further promote the expression of HO‐1 and NQO‐1, and upregulate various cellular antioxidant enzymes to protect tissues from oxidative stress 34–36 .…”

Sepsis-Induced Acute Lung Injury Is Alleviated by Small Molecules from Dietary Plants via Pyroptosis Modulation

“…In addition to the above-mentioned ones, a series of other small-molecule compounds from dietary plants, such as Hederasaponin C from Pulsatilla chinensis (Bunge) Regel, Fe-Curcumin-based nanoparticles with original curcumin that extracted from Rhizoma curcumae longae, 5-Hydroxymethylfurfural (5-HMF) from Codonopsis pilosula , Syringaresinol from Sargentodoxa cuneata , Chrysosplenol D from Chrysanthemum morifolium Ramat, physalin B from Physalis alkekengi L, baicalin from Scutellaria baicalensis George, etc., exert certain protective effect on ARDS induced by sepsis through a mechanism directly targeting the NLRP3/caspase-1/GSDMD axis, as shown in Table . The employed animal models were septic murine established by either LPS challenge or CLP procedure, and the involved common signaling pathways include TLR4/NF-κB, ,− ,− TXNIP, sirt1/CCL4, PI3K/Akt, Nrf2/HO-1, , TRAF6/HSP90 and MAPK ,, aside from the NLRP3/caspase-1/GSDMD axis. By analyzing the chemical structure of the above small-molecule compounds, we found that the top three categories of naturally derived compounds with ameliorative effect on sepsis-induced ARDs by rescuing pyroptotic cell death in pulmonary cells are respectively flavonoids and flavone (7 candidates), terpenoids (5 candidates), and polyphenol and phenolic acids (5 candidates), as illustrated in Figures and .…”