title: Suppression of NF-κB p65 nuclear translocation and tumor necrosis factor-α by Pongamia pinnata seed extract in adjuvant-induced arthritis.
abstract: Pongamia pinnata is a plant known for its therapeutic usage in Indian traditional medicine. Despite the controversy regarding toxic flavonoid and erucic acid content, the seed of this plant is consumed in tribal medicine and its oil is used in Ayurveda to treat psoriasis and arthritis. This study explored the potential anti-arthritic effects of a P. pinnata seed (hexane) extract (PSE) at non-lethal doses in an adjuvant-induced arthritic rat model; possible mechanisms of any observed effects were also explored. After establishing the lethal doses arising from oral exposure to the extract, the material was administered per os daily at two doses (0.3 g/kg/day; 0.5 g/kg/day) to arthritic rats. Other rats received indomethacin or vehicle (control). Treatments were performed for a total of 14 days. One day after the final exposure, the rats were euthanized to permit harvest of various cells, blood, and tissues for analyses. Paw diameter and tissue myeloperoxidase activity in the paws were evaluated as indices for edema and neutrophil infiltration into the tissue. The severity of arthritis in the experimental rats was assessed via measures of urinary hydroxyproline (HP) and glucosamine, and of serum pro-inflammatory TNFα and anti-inflammatory IL-10. The extent of NF-κB p65 nuclear translocation in peritoneal macrophages harvested from naïve rats and then treated in vitro was also assessed. The results indicated that exposure to PSE significantly decreased paw diameter, tissue myeloperoxidase level, and levels of urinary HP and glucosamine, as well as of serum TNFα and IL-10 in adjuvant-injected (arthritic) rats. In vitro PSE treatment also resulted in a marked inhibition of NF-κB p65 nuclear translocation in primary cultures of peritoneal macrophages. Thus, PSE appears to be able to prevent experimental arthritis, in part, by helping to maintain the balance between pro- and anti-inflammatory cytokines and by inhibiting NF-κB activation.
authors: Department of Physiology, University of Calcutta , Kolkata , India .
authors: Madhura
authors: M
authors: Bose
authors: Mousumi
authors: M
authors: Chakraborty
authors: Sourav
authors: S
authors: Bhattacharya
authors: Pushpak
authors: P
authors: Bhattacharjee
authors: Suvra
authors: S
authors: Mandal
authors: Manoj
authors: M
authors: Kar
authors: Roshnara
authors: R
authors: Mishra
mesh_terms: D021581:Active Transport, Cell Nucleus; D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D002478:Cells, Cultured; D005620:Freund's Adjuvant / Q000276:immunology; D005944:Glucosamine / Q000652:urine; D006909:Hydroxyproline / Q000652:urine*; D016753:Interleukin-10 / Q000097:blood; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D008515:Medicine, Ayurvedic; D033641:Millettia / Q000276:immunology*; D010936:Plant Extracts / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds; D051996:Transcription Factor RelA / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D010936:Plant Extracts; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D005620:Freund's Adjuvant; D005944:Glucosamine; D006909:Hydroxyproline
keywords: Adjuvant-induced arthritis; NF-κB p65 translocation; Pongamia pinnata seed