Background: Although emphysema destroys alveolar structures progressively and causes death eventually, no drug has been discovered to prevent, intervene, and/or resolve this life-threatening disease. We recently reported that sulfated caffeic acid dehydropolymer CDSO3 is a novel potent triple-action inhibitor of elastolysis, oxidation, and inflammation in vitro, and therefore, a potential anti-emphysema agent. However, the in vivo therapeutic potency, duration and mode of actions, and effective route remain to be demonstrated.
Methods: Emphysema was induced in rats with human sputum elastase (HSE) combined with cigarette smoke extract (CSE). CDSO3 at 5, 30, or 100 μg/kg was dosed to the lung or injected subcutaneously at 2, 6, or 24 h before or 1 or 24 h or 1 week after the HSE/CSE instillation. At 1 h or 48 h or on day 21-22 or day 28, lungs were examined for airway-to-blood injurious barrier damage; their elastolytic, oxidative, and inflammatory activities; lung luminal leukocytes infiltration; functional treadmill exercise endurance; and/or morphological airspace enlargement.
Results: CDSO3, when dosed to the lung at 30 or 100 μg/kg, but not via systemic subcutaneous injection, significantly (43-93 %) attenuated HSE/CSE-induced (1) barrier damage measured by luminal hemorrhage and protein leak; (2) elastolytic, oxidative, and inflammatory activities measured with elastase, reduced glutathione, and TNFα levels, respectively; (3) luminal neutrophil infiltration and tissue myeloperoxidase activity; (4) functional impairment of exercise endurance; and (5) airspace enlargement, in both preventive and interventional dosing protocols. Notably, the effects were shown to last for 24 h at the greater 100-μg/kg dose, and the 1-week-delayed administration was also capable of attenuating the development of emphysema.
Conclusions: CDSO3 is a novel, potent, long-acting, nonpeptidic macromolecule that inhibits HSE/CSE-induced elastolysis, oxidation, and inflammation in the lung and thereby attenuates the development of emphysema in rats, in both preventive and interventional manners, when administered locally to the lung.
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http://dx.doi.org/10.1007/s00408-014-9597-2 | DOI Listing |
Colloids Surf B Biointerfaces
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Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China; Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. Electronic address:
Ulcerative colitis is a recurring condition that causes inflammation and sores in the digestive system. Current clinical treatments for ulcerative colitis have limitations due to side effects and poor patient compliance. This study investigates the therapeutic potential of a novel drug delivery system, CA-Gel, which comprises caffeic acid (CA) stabilized by pectin nanoparticles within a poloxamer thermosensitive gel for rectal administration.
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State Key Laboratory of Component-based Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, PR China. Electronic address:
Ethnopharmacological Relevance: Cimicifuga heracleifolia Kom. (C. heracleifolia) has demonstrated efficacy in treating gastrointestinal disorders, including splenasthenic diarrhea.
View Article and Find Full Text PDFToxins (Basel)
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Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea.
The human colonic commensal enterotoxigenic (ETBF) is associated with chronic colitis and colon cancer. ETBF colonization induces colitis via the toxin (BFT). BFT secreted by ETBF cause colon inflammation via E-cadherin cleavage/NF-κB signaling.
View Article and Find Full Text PDFJ Chromatogr B Analyt Technol Biomed Life Sci
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School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China. Electronic address:
Xiaoyan Tuire Granule is a type of Chinese patent medicine that has been proven effective in treating respiratory tract infections. However, while it has been successfully introduced into clinical use, more knowledge is still needed regarding its chemical components and pharmacokinetics. This study investigated the chemical profile in the medicine and rat plasma by ultra high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Orbitrap-MS/MS).
View Article and Find Full Text PDFSci Rep
September 2024
Department of Pediatrics, College of Medicine and King, Khalid University Hospital, King Saud University, Medical City, PO Box-2925, 1146, Riyadh, Saudi Arabia.
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