Acute Lung Injury

Amiodarone, a benzofuran-based Class III antiarrhythmic agent, inhibits WT outward ionic current (IhERG) tails with an IC₅₀ of ∼45 nM. Amiodarone induces cell proliferation and myofibroblast differentiation via ERK1/2 and p38 MAPK signaling in fibroblasts. Amiodarone can be used in the research of both supraventricular and ventricular arrhythmias.

Isoferulic acid (3-Hydroxy-4-methoxycinnamic acid) is an orally active cinnamic acid derivative. Isoferulic acid exhibits hypoglycemic, antiviral, and antioxidant activities. Isoferulic acid can also inhibit fructose- and glucose-mediated protein glycation. Isoferulic acid can be used in the research of diseases such as diabetes.

Isorhapontigenin is an orally active dietary polyphenol. Isorhapontigenin acts as a potent antioxidant that reduces the production of reactive oxygen species (ROS). Isorhapontigenin promotes the binding of JUN to the AP-1 site on the SESN2 promoter, induces SESN2 transcription, triggers MAPK8-dependent JUN activation, and upregulates the expression of PPAR-α, PGC-1α and CPT-1A to facilitate fatty acid oxidation. Isorhapontigenin induces autophagy, apoptosis and preadipocyte differentiation; it inhibits tumor growth, cell invasion, NF-κB transcriptional activity, the PI3K/Akt signaling pathway, STAT1 phosphorylation and MMP-2 expression. Isorhapontigenin alleviates oxidative stress, inflammatory cytokine release and triglyceride accumulation; it increases intracellular ATP levels and promotes Nrf2 nuclear translocation. Isorhapontigenin improves insulin sensitivity in adipose tissue and glucose tolerance, and reduces postprandial blood glucose, insulin and free fatty acid levels. Isorhapontigenin is applicable to research on bladder cancer, liver injury, chronic obstructive pulmonary disease, acute lung injury and type 2 diabetes.

Kirenol is a diterpenoid compound, an orally active apoptosis inducer and signaling pathway regulator, with a K_d value of 5.47 μM against the target CK2. Kirenol promotes the cleavage of Bid into tBid, regulates the protein levels/phosphorylation of Bax, Bcl-2, p53 and p21, and induces caspase-independent apoptosis, S-phase cell cycle arrest, ROS accumulation and cytotoxicity in cancer cells. Kirenol activates the CK2/AKT and AMPK-mTOR-ULK1 pathways, inhibits the signaling of NF-κB, TGF-β/Smads and NLRP3 inflammasome, and regulates the GSK3β, BMP and Wnt/β-catenin pathways. Kirenol induces autophagy, mitophagy and osteoblast differentiation, promotes mitochondrial fusion, and exerts antioxidant, anti-inflammatory, antifibrotic, renoprotective, cardioprotective, neuroprotective and analgesic effects. Kirenol is applicable to research related to chronic myeloid leukemia, ischemic stroke, diabetic nephropathy, heart failure, acute lung injury and osteoporosis.

PXS-4728A is an orally active, selective VAP-1/SSAO inhibitor with an IC₅₀ of 5 nM and a K_i of 175 nM. PXS-4728A inhibits the expression of MMP-9. It reduces cell rolling, adhesion and migration, decreases cell infiltration levels, pro-inflammatory cytokines, chemokines and collagen deposition, and improves pulmonary function. PXS-4728A reduces the formation and progression of atherosclerotic plaques, and decreases blood lipid and blood glucose levels as well as body weight gain. PXS-4728A can be used in research related to chronic obstructive pulmonary disease, cystic fibrosis, acute pulmonary inflammation, acute lung injury, bronchiolitis obliterans syndrome, rhinovirus-exacerbated asthma, sepsis, Klebsiella pneumoniae pulmonary infection and atherosclerosis.

Hordenine (Ordenina; Peyocactine) is a multifunctional alkaloid with oral activity and blood-brain barrier penetration. Hordenine inhibits LPS-induced phosphorylation of p38, JNK, ERK1/2, p65, IκB, and AKT, prevents p65 nuclear translocation, and suppresses inflammatory cytokines and mediators. Hordenine promotes M2 macrophage polarization, restores blood-milk barrier integrity, alleviates oxidative stress by reducing ROS and MDA, and attenuates LPS-induced lung injury and pulmonary edema. Hordenine inhibits cAMP production, CREB phosphorylation, and MITF expression, thereby suppressing melanin synthesis in melanocytes and reconstructed epidermis. Hordenine activates the Wnt/β-catenin signaling pathway, promotes dermal papilla cell proliferation and hair shaft elongation, and accelerates hair regeneration. Hordenine activates DRD2, acts as a D3R partial agonist, α2A-AR full agonist, and 5-HT2A-R antagonist, and inhibits SERT and DAT. Hordenine inhibits α-synuclein accumulation and ameliorates motor deficits in Parkinson's disease models. Hordenine limits alcohol intake, reduces relapse drinking behavior, and modulates alcohol-induced conditioned place preference. Hordenine can be used for research on mastitis, skin pigmentation, acute lung injury, foodborne diseases, hair loss, Parkinson's disease, bacterial infections, and alcohol use disorder.

Olprinone (Loprinone) Hydrochloride is a potent and selective phosphodiesterase 3 (PDE3) inhibitor, with IC₅₀ values of 150, 100, 0.35, and 14 μM against PDE1, PDE2, PDE3, and PDE4, respectively. Olprinone Hydrochloride exerts comprehensive protective effects including anti-inflammatory, antioxidant, and anti-apoptotic activities by elevating intracellular cAMP levels and inhibiting the NF-κB and MAPK signaling pathways. Olprinone Hydrochloride can be used in studies related to lung injury, spinal cord injury, heart failure, myocardial ischemia-reperfusion injury, and cerebral ischemic injury.

Olprinone (Loprinone) is a potent and selective phosphodiesterase 3 (PDE3) inhibitor, with IC₅₀ values of 150, 100, 0.35, and 14 μM against PDE1, PDE2, PDE3, and PDE4, respectively. Olprinone exerts comprehensive protective effects including anti-inflammatory, antioxidant, and anti-apoptotic activities by elevating intracellular cAMP levels and inhibiting the NF-κB and MAPK signaling pathways. Olprinone can be used in studies related to lung injury, spinal cord injury, heart failure, myocardial ischemia-reperfusion injury, and cerebral ischemic injury.

CMIT/MIT (14.5% in water) (CMI/MI) is a mixture of CMIT and MIT, and is also a preservative and skin sensitizer. CMIT/MIT (14.5% in water) increases the levels of phosphorylated ERK1/2, p38, JNK1/2, p53, p21 and Bax, decreases the level of Bcl-2, and activates the Nrf-2/HO-1 signaling pathway. CMIT/MIT (14.5% in water) increases LDH release and lipid peroxidation levels, impairs antioxidant defense capacity, promotes pro-inflammatory cytokine release, induces apoptosis, triggers cell cycle arrest, exhibits neurotoxicity in neuroblastoma cells, and causes dysregulation of Th2/Th17 immune responses. CMIT/MIT (14.5% in water) can be used in studies related to allergy, atopic dermatitis and lung injury.

Gypenoside XLIX is a multifunctional bioactive compound that can be isolated from Gynostemma pentaphyllum, with a K_a value of 1.58 μM for its binding to SIRT1. Gypenoside XLIX acts as a PPAR-α agonist. It inhibits the activation of TLR4-mediated NF-κB signaling pathway by activating the Sirt1/Nrf2 signaling pathway, reduces ROS accumulation, and alleviates hepatic inflammatory injury in mice with sepsis-induced liver disease. Gypenoside XLIX targets SIRT1 to block YAP-NLRP3 activation and improve sepsis-induced cardiomyopathy. Gypenoside XLIX inhibits apoptosis (Apoptosis), pyroptosis (Pyroptosis), autophagy (Autophagy), lipid peroxidation, pro-inflammatory cytokines and anti-inflammatory cytokines. Gypenoside XLIX alleviates sepsis-induced splenic injury by inhibiting inflammation and oxidative stress, and mitigates sepsis-associated encephalopathy by targeting PPAR-α. Gypenoside XLIX prevents acute kidney injury by inhibiting IGFBP7/IGF1R-mediated programmed cell death and inflammation. Gypenoside XLIX inhibits the expression and activity of vascular cell adhesion molecule-1 in cytokine-induced human endothelial cells. Gypenoside XLIX is applicable to research related to acute liver injury, lung injury, cardiomyopathy, acute splenic injury, sepsis-associated encephalopathy, acute kidney injury, atherosclerosis and chronic inflammation.

Calcium gluconate is an orally effective calcium salt supplement. Calcium gluconate reduces elevated serum potassium, decreased serum calcium, and postoperative myalgia associated with succinylcholine administration. Calcium gluconate restores calcium homeostasis, skeletal integrity, bone mineralization and bone density, and maintains levels of parathyroid hormone, bone resorption markers and osteoclasts. Calcium gluconate reverses LPS (HY-D1056)-induced ERK phosphorylation, inflammatory cytokine release and acute lung injury, alleviates airway inflammatory damage and suppresses immune responses. Calcium gluconate can be used in research related to postoperative myalgia, osteoporosis/osteomalacia and acute lung injury.

Praeruptorin E is an orally active pyranocoumarin compound. Praeruptorin E can be isolated from the dried roots of Peucedanum praeruptorum Dunn. Praeruptorin E reduces the expression of NF-κB. Praeruptorin E upregulates the expression of PXR and CYP3A4. Praeruptorin E inhibits Th2 cytokines, TNF-α, IL6, MPO, and blocks the Ca²⁺ slow channel. Praeruptorin E promotes pulmonary tissue repair and relaxes porcine coronary artery strips. Praeruptorin E protects mice from lipopolysaccharide- and hydrochloric acid-induced acute lung injury. Praeruptorin E can be used in studies related to asthma and acute lung injury.

Rotundic acid is an orally effective triterpenoid with a K_d value of 51.3 µM for PTP1B. Rotundic acid downregulates the AKT/mTOR pro-survival pathway and modulates the MAPK pathway. Rotundic acid induces cell cycle S-phase arrest, DNA damage and apoptosis; it inhibits migration, invasion, angiogenesis and proliferation of cancer cells. Rotundic acid improves leptin sensitivity, regulates gut microbiota and reduces cellular senescence. Rotundic acid can be used in research related to hepatocellular carcinoma, obesity, aging, acute lung injury and type 2 diabetes.

Rubiadin-1-methyl ether is an orally potent NF-κB p65 inhibitor and autophagy inhibitor. Rubiadin-1-methyl ether inhibits RANKL-induced phosphorylation and nuclear translocation of p65, suppresses BECN1 transcription, blocks LC3 conversion and autophagosome formation, thereby reducing the levels of BECN1 mRNA and Beclin1 protein. Rubiadin-1-methyl ether inhibits osteoclastogenesis, cell proliferation, macrophage M2 polarization and the TGF-β1 signaling pathway, and effectively alleviates pulmonary inflammation. Rubiadin-1-methyl ether is widely used in research on osteoporosis, pulmonary fibrosis, idiopathic pulmonary fibrosis, acute lung injury and other related diseases.

Iridin is an orally active natural isoflavone. Iridin inhibits the PI3K/AKT and PKM2 signaling pathways, and downregulates the JAK/STAT and NF-κB pathways. Iridin induces Fas-mediated extrinsic apoptosis, G2/M cell cycle arrest, and inhibits cell proliferation. Iridin reduces inflammation, inhibits ROS production, suppresses glycolysis, and also exhibits antioxidant and antidiabetic activities. Iridin can be used in research related to gastric cancer and acute lung injury.

Eicosatetraynoic acid (ETYA) is a non-metabolizable analog of Arachidonic acid (HY-109590) and also an inhibitor of the lipoxygenase (LOX)/cyclooxygenase (COX) pathway (ID₅₀ = 8 μM and 4 μM). Eicosatetraynoic acid acts as a suicide substrate to inhibit the production of inflammatory mediators such as leukotrienes and prostaglandins. Eicosatetraynoic acid acts directly on cell membranes and membrane proteins to exert a wide range of effects, including blocking potassium channels, increasing cell membrane fluidity, elevating intracellular calcium levels, inhibiting DNA synthesis in tumor cells, inducing differentiation of certain cells, and specifically inhibiting the assembly and replication of orthopoxviruses. Eicosatetraynoic acid alleviates acute lung injury induced by chemicals such as phosgene.

Physalin B is an orally active anti-inflammatory and anticancer agent. Physalin B can be isolated from Physalis alkekengi L. var. Franchetii. Physalin B inhibits the activation of the NF-κB, NLRP3 inflammasome, STAT3, PI3K/Akt and Hedgehog signaling pathways, regulates the phosphorylation levels of GSK-3β, p38 MAPK, ERK1/2 and JNK, and promotes the nuclear translocation of NRF2. Physalin B reduces the levels of pro-inflammatory cytokines and factors, induces mitochondrial reactive oxygen species (mito-ROS) production, Apoptosis, G2/M cell cycle arrest and incomplete Autophagy, alters cytoskeleton structure and alleviates oxidative stress. Physalin B reduces cancer cell viability, ameliorates liver and lung tissue damage and alleviates liver fibrosis. Physalin B can be used in research related to ulcerative colitis, breast cancer, acute lung injury, colon cancer, non-alcoholic steatohepatitis, liver fibrosis, lung cancer, pancreatic cancer, lymphoma, ovarian cancer, sarcoma and leukemia.

113-N16B is an ionizable cationic lipid that can be used for the synthesis of lipid nanoparticles. 113-N16B delivers mRNA to pulmonary endothelial cells. 113-N16B can be formulated as a component into hybrid lipid nanoparticles for lung-specific delivery of mRNA (including MFSD7C mRNA and luciferase mRNA) in mice. 113-N16B is applicable to research related to lymphangioleiomyomatosis, sickle cell disease, and hemolysis-induced lung injury.

GSK1995057 is a human monoclonal antibody (mAb) targeting TNFRSF1A. GSK1995057 selectively binds to TNFR1, blocks the binding of TNF-α and LT-α, and does not interfere with TNFR2 signaling. GSK1995057 inhibits the activation of NF-κB, JNK and MAPK pathways, alleviates apoptosis (apoptosis) and inflammatory responses (inhibiting IL-1β, IL-6, IL-10, TNF-α), and prevents viability loss of human nucleus pulposus cells. GSK1995057 inhibits the expression of cytokines and neutrophil adhesion molecules in human pulmonary microvascular endothelial cell monolayers, and reduces inflammatory responses and lung injury symptoms in non-human primates. GSK1995057 forms complexes with HAVH autoantibodies, thereby activating TNFR1 and triggering the release of cytokines and IL-8 in human cells. GSK1995057 can be used in research related to intervertebral disc degeneration and acute lung injury.

Karacoline is an orally active PPARγ activator and ERK/JNK MAPK inhibitor. Karacoline restricts ROS production, maintains mitochondrial membrane potential, and inhibits pulmonary cell apoptosis. Karacoline inhibits NF-κB pathway activation, reduces acetylation levels of p65 and the expression of MMP14 and MMP9, enhances the expression of type II collagen (collagen II) and aggrecan (aggrecan), and suppresses extracellular matrix degradation. In a mouse model of sepsis-induced acute lung injury, Karacoline alleviates lung injury, inhibits the release of IL-1β, IL-6 and TNF-α, increases the Bcl-2/BAX ratio, and reduces caspase 3 expression. Karacoline can be used in research related to acute lung injury and intervertebral disc degeneration.