1. Synthesis and Comprehensive in Vivo Activity Profiling of Olean-12-en-28-ol, 3 beta-Pentacosanoate in Experimental Autoimmune Encephalomyelitis: A Natural Remyelinating and Anti-Inflammatory Agent
- Author
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Halil Senol, Ozden Ozgun-Acar, Aydan Dağ, Ahmet Eken, Hüseyin Guner, Zaliha Gamze Aykut, Gulacti Topcu, Alaattin Sen, Aykut, Zeliha Gamze, ŞENOL, HALIL, DAĞ, AYDAN, and TOPÇU, GÜLAÇTI
- Subjects
Temel Bilimler (SCI) ,Pharmaceutical Science ,Pharmacy ,1-Phosphate Receptor Modulator ,ÇOK DİSİPLİNLİ BİLİMLER ,Sağlık Bilimleri ,Clinical Medicine (MED) ,Analytical Chemistry ,Pharmaceutical Chemistry ,Drug Discovery ,FARMAKOLOJİ VE ECZACILIK ,Mechanisms ,Klinik Tıp (MED) ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,PHARMACOLOGY & PHARMACY ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Medical Progress ,PHARMACOLOGY & TOXICOLOGY ,Multidisciplinary ,Moleküler Biyoloji ,Temel Bilimler ,Life Sciences ,Genel Farmakoloji, Toksikoloji ve Eczacılık ,Farmakoloji (tıbbi) ,MOLECULAR BIOLOGY & GENETICS ,İlaç Rehberleri ,Farmakoloji ve Toksikoloji ,Natural Sciences (SCI) ,Molecular Medicine ,Natural Sciences ,Fingolimod Treatment ,Oleanane ,Capparis-Ovata ,Farmakoloji ,Farmasötik Kimya ,Life Sciences (LIFE) ,Gene-Expression ,Molecular Biology and Genetics ,Meslek Bilimleri ,Drug Guides ,Yaşam Bilimleri ,Health Sciences ,Professional Sciences ,Farmakoloji, Toksikoloji ve Eczacılık (çeşitli) ,Eczacılık ,Molecular Biology ,Moleküler Biyoloji ve Genetik ,Pharmacology ,Multidisipliner ,MULTIDISCIPLINARY SCIENCES ,Organic Chemistry ,Infiltration ,Doğa Bilimleri Genel ,Triterpenoids ,Pharmacology and Therapeutics ,Multiple-Sclerosis ,NATURAL SCIENCES, GENERAL ,Complementary and alternative medicine ,Yaşam Bilimleri (LIFE) - Abstract
Multiple sclerosis (MS) treatment has received much attention, yet there is still no certain cure. We herein investigate the therapeutic effect of olean-12-en-28-ol, 3 beta- pentacosanoate (OPCA) on a preclinical model of MS. First, OPCA was synthesized semisynthetically and characterized. Then, the mice with MOG35-55-induced experimental autoimmune/ allergic encephalomyelitis (EAE) were given OPCA along with a reference drug (FTY720). Biochemical, cellular, and molecular analyses were performed in serum and brain tissues to measure anti-inflammatory and neuroprotective responses. OPCA treat-ment protected EAE-induced changes in mouse brains maintaining blood-brain barrier integrity and preventing inflammation. Moreover, the protein and mRNA levels of MS-related genes such as HLD-DR1, CCL5, TNF-alpha, IL6, and TGFB1 were significantly reduced in OPCA-treated mouse brains. Notably, the expression of genes, including PLP, MBP, and MAG, involved in the development and structure of myelin was significantly elevated in OPCA-treated EAE. Furthermore, therapeutic OPCA effects included a substantial reduction in pro-inflammatory cytokines in the serum of treated EAE animals. Lastly, following OPCA treatment, the promoter regions for most inflammatory reGülators were hypermethylated. These data support that OPCA is a valuable and appealing candidate for human MS treatment sİnce OPCA not only normalizes the pro-and anti-inflammatory immunological bias but also stimulates remyelination in EAE.
- Published
- 2023