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Study of indigo alkaloid on therapeutic of pain and inflammation

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Author(s):
Ricardo Jose Dunder
Total Authors: 1
Document type: Doctoral Thesis
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
Defense date:
Examining board members:
Alba Regina Monteiro Souza Brito; Sisi Marcondes; Edson Rosa Pimentel; Adair Roberto Soares dos Santos; Stella Regina Zamuner
Advisor: Alba Regina Monteiro Souza Brito
Abstract

The inflammation is an immune system response to pathogens, chemical or physical traumas; this evolution may result in damage, or become chronic. It is a complex phenomenon, which involves several mediators, such as NF-?B that promotes the release of cytokines and pro-inflammatory enzymes followed by leukocyte infiltration; resulting in five cardinal signs: heat, redness, tumour, pain and loss of function. The application of secondary metabolites of plants is an alternative for treatment of pain and inflammation. Among the metabolites, the alkaloids receive special emphasis such as morphine, a potent analgesic. In this work, the anti-inflammatory and analgesic potential of indigo alkaloid (1.5, 3.0 e 6.0 mg/kg), obtained from Indigofera truxillensis (Leguminosae) was observed in edema models (xylene and arachidonic acid ear edema and carrageenan hind paw) and cellular infiltration (granuloma cotton pellet e pleurisy). In these models, indigo presented significant reduction of edema and cellular infiltration, mainly polimorphonuclears. ELISA analyses revealed that alkaloid decreased the levels of MPO, nitrite and nitrate, PGE2 and TNF-?, as well as the expression of COX-2 by western blot and immunohistochemistry. The reduction of mediators suggests that indigo could have anti-inflammatory an action that involves NF-?B, this activity was seen again by western blot. Randall & Selitto, abdominal writhing and formalin models of inflammatory pain were also performed and the alkaloid, over again, showed significant statistic response, probably by the reduction of inflammatory mediators. Indigo was also evaluated in neurogenic models of pain and demonstrated an increase of the latency in thermal stimuli (tail flick and hot plate tests) and capsaicin tests implicated with TRPV1 activity, however, the alkaloid did not show any interaction with opioid receptors in the formalin test with naloxone reversal. These results suggest that indigo has an anti-inflammatory action that may be involved with COX-2 and NF-?B, the reduction of these mediators contributed to the analgesic action in inflammatory pain and also to the reduction in peripheral pain (AU)