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Milonine, a Morphinandienone Alkaloid, Has Anti-Inflammatory and Analgesic Effects by Inhibiting TNF-α and IL-1β Production

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Abstract

Milonine is a morphinandienone alkaloid from Cissampelos sympodialis Eichl (Menispermaceae), a plant used in Brazil to treat inflammatory disorders. In this study, we evaluated the anti-inflammatory and analgesic activity of milonine (MIL) by using classical experimental models of inflammation and nociception. The results showed that MIL reduced the paw edema formation induced by lipopolysaccharide, prostaglandin E2, and bradykinin, without interfering with the serotonin-induced edema. With respect to the nociception experiments, MIL decreased the exudate into the peritoneum induced by acetic acid, maintaining the tissue morphology. The alkaloid was able to inhibit the peritonitis induced by carrageenan, decreasing mainly the migration of polymorphonuclear cells, without altering the mononuclear cell number, and reduced the levels of TNF-α and IL-1β in the peritoneum. In addition, MIL was able to decrease the frequency of abdominal writhing induced by acetic acid but did not increase the latency time of the animals in the hot plate test. MIL significantly reduced the nociceptive behavior of paw licking induced by formalin only at the second phase of the test. In conclusion, we demonstrate that milonine has anti-inflammatory and anti-nociceptive activities by inhibiting mediators essential for the inflammatory process.

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Acknowledgments

This study was financially supported by INCT para Controle do Câncer and CAPES/Brazil.

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Authors and Affiliations

  1. Laboratory of Immunopharmacology, Department of Physiology and Pathology, Federal University of Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil

    Larissa Rodrigues Silva, Luiz Henrique Agra Cavalcante-Silva & Márcia Regina Piuvezam

  2. Department of Pathology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270-901, Brazil

    Adriano Francisco Alves

  3. Laboratory of Psychopharmacology, Department of Physiology and Pathology, Federal University of Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil

    Renan Marinho Braga & Reinaldo Nóbrega de Almeida

  4. Laboratory de Phytochemistry, Department of Pharmacy, Federal University of Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil

    José Maria Barbosa-Filho

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  1. Larissa Rodrigues Silva
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  3. Luiz Henrique Agra Cavalcante-Silva
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Correspondence to Márcia Regina Piuvezam.

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The experiments were conducted according to the Ethics Committee for the Use of Animals (CEUA/Federal University of Paraiba/João Pessoa/PB/Brazil) under the protocol number 003/2016.

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Silva, L.R., Alves, A.F., Cavalcante-Silva, L.H.A. et al. Milonine, a Morphinandienone Alkaloid, Has Anti-Inflammatory and Analgesic Effects by Inhibiting TNF-α and IL-1β Production. Inflammation 40, 2074–2085 (2017). https://doi.org/10.1007/s10753-017-0647-9

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