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

Autor: Halil Senol, Ozden Ozgun-Acar, Aydan Dağ, Ahmet Eken, Hüseyin Guner, Zaliha Gamze Aykut, Gulacti Topcu, Alaattin Sen
Přispěvatelé: Aykut, Zeliha Gamze, ŞENOL, HALIL, DAĞ, AYDAN, TOPÇU, GÜLAÇTI
Jazyk: angličtina
Rok vydání: 2023
Předmět:
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)
Zdroj: Journal of Natural Products
Popis: 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.
Databáze: OpenAIRE
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