Epimedium flavonoids ameliorate experimental autoimmune encephalomyelitis in rats by modulating neuroinflammatory and neurotrophic responses.
The present study was designed to determine whether epimedium flavonoids (EF) had effect on the development of experimental autoimmune encephalomyelitis (EAE) in rats and to elucidate its underlying mechanisms. EAE was induced by immunization of adult female Lewis rats with partially purified myelin basic protein (MBP) prepared from guinea-pig spinal cord homogenate. EF was administrated intragastrically once a day after immunization until day 14 post immunization (p.i.). Histopathological staining, enzyme-linked immunosorbent assay (ELISA), biochemical methods and western blotting approaches were used to evaluate the disease incidence and severity, neuroinflammatory and neurotrophic response in the central nervous system (CNS). Intragastrical administration of EF (20 and 60 mg/kg) significantly reduced clinical score of neurological deficit in EAE rats; alleviated demyelination and inflammatory infiltration; and inhibited astrocytes activation, production of proinflammatory molecules such as interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), nitric oxide (NO) and nuclear transcription factor (NF-κB) in the spinal cord of EAE rats. Treatment with EF also enhanced the expression of 2', 3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) and nerve growth factor (NGF), increased the number of oligodendrocytes and protected the ultrastructure of myelin sheaths and axons in the spinal cord of EAE rats. Our results showed that EF inhibited the development of partial MBP-induced EAE in rats. This effect involved reducing neuroinflammation and enhancing myelination and neurotrophins and our findings suggest that EF may be useful for the treatment of multiple sclerosis.
Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing Geriatric Medical Research Center, 45 Changchun Street, Beijing 100053, PR China.
Lin-Lin
LL
Yin
Li-Li
LL
Lin
Lan
L
Zhang
Lin
L
Li
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003711:Demyelinating Diseases / Q000209:etiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D034181:Epimedium / Q000737:chemistry*; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use*; D009186:Myelin Sheath / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D009414:Nerve Growth Factors