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Abstract: Awara (Astrocaryum vulgare M.) is a palm fruit mainly used in nutrition. We analysed the pulp oil for fatty acid, tocopherol, carotenoid, and phytosterol and we evaluated whether this oil may attenuate inflammation in vivo. In an endotoxic shock model, awara pulp oil treatment decreased pro-inflammatory cytokines and increased anti-inflammatory cytokines. In a pulmonary inflammation model, awara pulp oil treatment reduced eosinophil and lymphocyte numbers recovered into the broncho-alveolar lavages. These results suggest that awara pulp oil administration can efficiently counteract an acute and chronic inflammatory response in vivo that is probably mediated by fatty acids and minor compounds. [Copyright &y& Elsevier]

Ethnopharmacological relevance Morinda citrifolia L. (Noni) is a medicinal plant used in Polynesia for many properties such as anti-inflammatory, anti-diabetic and antineoplastic effects. Recent studies showed that noni juice have anti-oxidant and acute anti-inflammatory activities likely due to polyphenols, iridoids and vitamin C content. The present study was undertaken to evaluate chronic anti-inflammatory and spasmolytic effects of noni juice. Materials and methods Therefore, we evaluated the effect of oral or intraperitoneal administrations of noni juice in vivo on the lung inflammation in ovalbumin (OVA) sensitized Brown Norway rat (with prednisolone 10 mg/kg intraperitoneously as reference compound) and the ex vivo effect of noni juice on BaCl 2 (calcium signal) or methacholine (cholinergic signal) induced spasms in jejunum segments. Results We found that noni juice (intraperitoneously 2.17 mL/kg and orally 4.55 mL/kg) reduced the inflammation in OVA-sensitized Brown Norway rat with regard to the decreased number of inflammatory cells in lung (macrophages minus 20–26%, lymphocytes minus 58–34%, eosinophils minus 53–30%, neutrophils minus 70–28% respectively). Noni juice demonstrated a dose-dependent NO scavenging effect up to 8.1 nmol of nitrites for 50 µL of noni juice. In addition noni juice inhibited (up to 90%) calcium and cholinergic induced spasms on the jejunum segments model with a rightward shift of the concentration response curve. Conclusion We describe for the first time that noni juice demonstrate (1) a chronic anti-inflammatory activity on sensitized lungs along with (2) a spasmolytic effect integrating a calcium channel blocker activity component. [ABSTRACT FROM AUTHOR]

Summary Nearly 50% of human malignancies exhibit unregulated RAS-ERK signaling; inhibiting it is a valid strategy for antineoplastic intervention. Upon activation, ERK dimerize, which is essential for ERK extranuclear, but not for nuclear, signaling. Here, we describe a small molecule inhibitor for ERK dimerization that, without affecting ERK phosphorylation, forestalls tumorigenesis driven by RAS-ERK pathway oncogenes. This compound is unaffected by resistance mechanisms that hamper classical RAS-ERK pathway inhibitors. Thus, ERK dimerization inhibitors provide the proof of principle for two understudied concepts in cancer therapy: (1) the blockade of sub-localization-specific sub-signals, rather than total signals, as a means of impeding oncogenic RAS-ERK signaling and (2) targeting regulatory protein-protein interactions, rather than catalytic activities, as an approach for producing effective antitumor agents. [ABSTRACT FROM AUTHOR]