gamma-oryzanol and Inflammation

Rice bran contains important bioactive phytochemicals. Among these phytochemicals, steryl ferulates including γ-oryzanol and its major components such as cycloartenyl ferulate (CAF), 24-methylenecycloartanyl ferulate (24-mCAF), β-sitosteryl ferulate (β-SF), and campesteryl ferulate have been intensively studied due to their crucial roles in pathological processes. On the basis of experimental studies published during the last decade in relation to antioxidant, anti-inflammatory, anti-ulcerogenic, hypolipidemic, anti-neoplastic, anti-diabetic, and anti-allergic phenomena, these bioactive phytochemicals are reviewed in this paper. Particularly, in vivo and in vitro studies have clarified that rice bran phytosteryl ferulates mediate anti-inflammatory effects by down-regulating the inflammatory transcription factor, nuclear factor κB (NF-κB), which in turn reduces expression of inflammatory enzymes such as COX-2 and iNOS, and proinflammatory cytokines such as IL-1β, IL-6 and TNF-α. Moreover, rice bran phytosteryl ferulates up-regulate blood adiponectin levels via indirect activation of peroxisomal proliferator-activated receptor γ (PPARγ) through NF-κB inhibition. In this review, we discuss potential pharmacological aspects of rice bran phytosteryl ferulates in the clinical setting.

Topics: Adiponectin; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Coumaric Acids; Cyclooxygenase 2; Humans; Hypersensitivity; Immunity; Inflammation; Interleukin-6; Mice; NF-kappa B; Nitric Oxide Synthase Type II; Oryza; Oxidative Stress; Phenylpropionates; Phytosterols; Plant Extracts; PPAR gamma; Tumor Necrosis Factor-alpha; Up-Regulation

During the screening of selective DNA polymerase (pol) inhibitors, we isolated cycloartenyl trans-ferulate (CAF), which is a major component of γ-oryzanol, which is a byproduct formed during the production of Japanese rice wine "sake". CAF selectively inhibited the activity of mammalian A, B, and X pol families, but Y family pols were not affected. CAF did not influence the activities of plant or prokaryotic pols, nor the activity of other DNA metabolic enzymes tested. Individual chemical components of CAF, including cycloartenol (CA) and ferulic acid (FA), did not inhibit pol enzyme activities. CAF suppressed TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation in the mouse ear, but CA and FA did not. The ability to inhibit mammalian pol enzymes in vitro was positively correlated with their propensity to suppress inflammation in vivo. These results suggest that this byproduct formed during the sake-brewing process is useful as an anti-inflammatory agent.

Topics: Animals; Anti-Inflammatory Agents; Cattle; Coumaric Acids; DNA-Directed DNA Polymerase; Enzyme Inhibitors; Female; Humans; Inflammation; Mice; Mice, Inbred ICR; Nucleic Acid Synthesis Inhibitors; Oryza; Plant Extracts; Rats; Seeds; Waste Products; Wine

IgE-targeting therapy could provide significant progress in the treatment of allergic inflammation. In this study, we examined the effect of cycloartenyl ferulate (cycloartenol ferulic acid ester; CAF), a natural product from rice bran oil-derived gamma-oryzanol, on allergic reaction. When CAF and gamma-oryzanol were injected intradermally with anti-DNP IgE into the dorsal skin of rats, the passive cutaneous anaphylaxis reaction induced by DNP-HSA was attenuated. CAF and gamma-oryzanol also inhibited the degranulation of DNP-IgE sensitized RBL-2H3 mast cells stimulated with anti-DNP-HSA. IgE conjugated with CAF could not be detected by anti-IgE antibody in the ELISA analysis. Although incubation of IgE with CAF did not decrease the amount of IgE, it was possible to precipitate IgE by centrifugation. These results demonstrate that CAF captures IgE, prevents it from binding to FcepsilonRI, and attenuates mast cell degranulation.

Topics: Animals; Antibodies, Anti-Idiotypic; Cell Degranulation; Coumaric Acids; Dinitrophenols; Enzyme-Linked Immunosorbent Assay; Hypersensitivity; Immunoglobulin E; Inflammation; Male; Mast Cells; Oryza; Passive Cutaneous Anaphylaxis; Phenylpropionates; Phytotherapy; Plant Extracts; Plant Oils; Rats; Rats, Sprague-Dawley; Receptors, IgE; Rice Bran Oil; Serum Albumin; Skin