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Ethnopharmacological relevance Atropa acuminata Royle Ex Lindl. has been widely used in folk medicine for several inflammatory disorders such as arthritis, asthma, conjunctivitis, encephalitis, pancreatitis, peritonitis, acute infections and neuroinflammatory disorders. Aim of the study Our aim was to evaluate Atropa acuminata for its anti-inflammatory properties and to delineate its possible mechanism of action on the modulation of the inflammatory mediators. Materials and methods We investigated the inhibitory action of ethanolic extract of Atropa acuminata (AAEE) on production of NO, TNF-α and IL-1β in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and also assayed it for COX 1/2 and 5-LOX inhibitory activities. Next AAEE was tested in acute inflammatory animal models., carragenean induced rat paw edema, carragenean induce pleurisy in rats and vascular permeability in mice and the effects on NO, PGE 2 and LTB 4 production in the pleural fluid and paw exudates were evaluated. In addition the effects on leukocyte migration and exudation and vascular permeability were also observed. Results Our findings summarized novel anti-inflammatory mechanisms for Atropa acuminata based on dual in vitro cyclooxygenase 1/2/ and 5-Lipoxygenase inhibitory activities and also significant downregulation of nitric oxide (NO) and pro-inflammatory cytokin (TNF-α and Il-1 β) release in LPS-stimulated RAW 246.7 macrophage cell line. In acute inflammatory models in vivo (carragenean induced edema, carragenean induced pleurisy in rats and vascular permeability in mice), AAEE exhibited an extensive diverse mechanism for anti-inflammatory properties. This was indicated on the basis of dose dependent suppression of multi targeted inflammatory mediators., NO, TNF-α and IL-1β, eicosanoids., PGE 2 and leukotrienes., LTB 4 along with significantly decreased leucocyte migration, exudation and decreased vascular permeability. These effects were more potent and prolonged than traditional NSAIDS, thereby indicating fewer side effects. AAEE was found to be safe for long term administration, as confirmed by the results of acute toxicity studies and MTT assay. The complex mode of action of the herbs was attributed possibly due to the high polyphenolic, flavanol and flavonoid content present in the extracts as observed by means of quantitative screening for phytochemicals. Conclusion Our study provides scientific evidence to support the traditional anti-inflammatory uses of Atropa acuminata and is probably due to inhibitory effects on multiple inflammatory mediators which indicates a promising potential for the development of a strong anti-inflammatory agent from this plant.

Ethnopharmacological relevance Atropa acuminata has been widely used in traditional medicine against arthritis and several associated inflammatory disorders. Aim of the study The present study was undertaken to investigate the anti-arthritic activities of ethanolic extract of Atropa accuminata (AAEE) and to explore the probable mechanism of action. Materials and methods The anti-arthritic activity of AAEE was evaluated within a dose range of 125–500 mg/kg b.w. in adjuvant induced-arthritis in male wistar rats. An array of pro-inflammatory mediators (PGE2 NO, IL-1β and LTB4) and T-cell-mediated cytokines (IL-2, TNF-a, IFN-c, IL-4, IL-10, IL-12, IL-17, IL-6) were assayed in arthritic paw tissue homogenate of the treated animals. In addition the effects on arthritic lesions, changes in body weight; haematological (Hb, ESR, WBC and RBC) and biochemical parameters (SOD, GSH, GR) and the serum markers (CRP, RF) were also observed. Results Significant anti-arthritic activity was observed for AAEE in the polyarthiritis test both in the developing and developed phase of the disease. This was associated with dose dependant suppression of pro-inflammatory mediators (PGE 2 , NO, IL-1β and LTB 4 )., Th1-Th17 cytokines (IL-2, TNF-α, IFN-γ, IL-12, IL-17, IL-6) and upregulation of Th2 cytokines (IL-4 and IL-10). AAEE was also observed to protect rats against the primary and secondary arthritic lesions, body weight changes and haematological perturbations. In addition, inhibitory effects of AAEE on biochemical parameters and the serum markers further confirmed that it reduced signs on chronic inflammatory responses. Conclusion The present investigation therefore suggested that AAEE is a potent anti-arthritic agent. The multipronged attack on the inflammatory mediators and T-helper cytokines and strong potency of AAEE may have relevance for inhibition of the chronic inflammatory responses in arthritis.