Potent anti-inflammatory compounds identified in Zingiber officinale Roscoe var. rubrum Theilade: Mechanisms of action in psoriasis
Psoriasis is an autoimmune inflammatory skin disease associated with aberrant activation of T and B-lymphocytes. Increasing evidence indicates that T-helper 1 (Th1) and Th17 lymphocyte subsets play key roles in the immunopathogenesis of the disease. In such a setting, activated Th1/Th17 cells interact with keratinocytes leading to their proliferation and hyperplasia. Our studies are focused on developing new approaches for targeted therapy for psoriasis.
Recent studies from our laboratories have identified therapeutic effects for compounds extracted from the ginger species Zingiber officinale Roscoe var. rubrum Theilade, on pathogenic mechanisms in psoriasis. Initially, the therapeutic effects of chloroform extract (HB02) and selected fractions were assessed for their ability to suppress the production of pro-inflammatory mediators produced by macrophage. Four fractions, F5, F6, F7 and F10 with dual suppressive effects on NO and PGE2 production were identified. The fractions had higher potency than L-NAME, a specific inhibitor of iNOS, and exhibited comparable effects to indomethacin in inhibiting of PGE2. F6 had particularly potent inhibitory effects on inhibiting NO (IC50=6.7±2.7µg/ml) and suppressing iNOS gene transcription by 82.3±3.73% at 20µg/ml. Two compounds, 6-shogaol and a ferulate derivative were isolated from F6. Interestingly, the 2 compounds had additive effects in down-regulating iNOS and il23 gene transcription. These compounds may, therefore, be key components responsible for the anti-inflammatory effects of HB02. Current experiments are focused on mechanisms of action and therapeutic efficacy of these compounds on suppressing psoriasis involving chemokine and cytokine production and keratinocytes proliferation using an in vitro human psoriatic skin model.
Keywords: Psoriasis, Zingiber officinale Roscoe var. rubrum Theilade, 6-shogaol, ferulate derivative
Acknowledgement: 1. Standards and Industrial Research Institute of Malaysia (SIRIM Berhad), Malaysia
2. Ministry of Science, Technology & Innovation (MOSTI), Malaysia