Immunomodulatory effects of Zingiber officinale Roscoe var. rubrum (Halia Bara) on inflammatory responses relevant to psoriasis
Psoriasis is a chronic autoimmune skin disease characterised by hyperplasia of epidermal keratinocytes and the accumulation of activated immune cells at sites of the disease. The disease is associated with aberrant activation of phagocytes, T-lymphocytes and the production of pro-inflammatory cytokines and chemokines. This thesis examines the therapeutic efficacy and mechanisms of action of the ginger species Halia Bara, or Zingiber officinale Roscoe var. rubrum (ZOR), on key immunopathogenic mechanisms relevant to psoriasis. In-depth experiments first determined the effect of a ZOR extract in chloroform (HB02) and its fractions on nitric oxide (NO) and prostaglandin E2 (PGE2) production. The results of these experiments showed that HB02 and its fractions efficiently inhibited NO and PGE2 production by activated macrophages. Extensive fractionation and characterisation experiments succeeded in identifying two compounds 6-shogaol (6S) and 1-dehydro-6-gingerdione (GD) with potent inhibitory effects on NO and PGE2. These effects were comparable to dexamethasone and indomethacin. Studies on the effects of HB02, its fractions and compounds showed inhibitory effects on the level of mRNA for iNOS, TNFα, IL-12p40 and IL-23p19 in pre-treatment experiments of macrophages. Studies of cell migration showed that the fractions and compounds from ZOR inhibited the migration of polymorphonuclear neutrophils (PMNs) through human vascular endothelial cells (HUVEC) by influencing CD11b expression and CD62L shedding. Further studies showed that the ZOR samples also inhibited the activation of CD8+ cytotoxic T-lymphocytes and reduced CD25 and CD69 expression. Furthermore, an in vitro model of epidermal inflammation showed that ZOR directly inhibits keratinocyte proliferation and the production of IL-20 and IL-8, both key psoriasis-promoting cytokines. The studies reported in this thesis provide experimental evidence for potent anti-inflammatory properties of ZOR and for potential mechanisms of action in ameliorating psoriasis.
AuthorsNordin, Nurul Izza
- Theses