Abstract

Himatanthus drasticus (Mart.) Plumel belongs to the Apocynaceae family and the latex from its trunk bark (Hd) is known as “janaguba milk”. This latex is widely used in Northeast Brazil, mainly in the Cariri region, for its gastroprotective, anti-inflammatory, and antitumor properties. The objective of this study was to investigate a triterpene-rich fraction (FJNB) from H. drasticus latex on acute models of nociception and inflammation and to clarify its mechanisms of action. Wistar rats or Swiss mice were subjected to the carrageenan-induced paw edema test or the formalin test, respectively, after the acute oral treatment with FJNB. The inflamed paws from the carrageenan-induced paw edema and formalin tests were processed for histological and immunohistochemical assays, respectively. The results were analyzed by ANOVA and considered significant at P<0.05. FJNB (10 mg/kg) decreased the paw edema by 25% at the 3rd h after the carrageenan injection. Indomethacin, used as reference, inhibited the paw edema by 59% at the same time-point. In the formalin test, FJNB inhibited the 1st phase by 27, 49, and 52% and the 2nd phase by 37, 50, and 67%, at the doses of 1, 5, and 10 mg/kg, respectively. In addition, FJNB significantly inhibited the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and the inflammatory cytokine tumor necrosis factor (TNF)-alpha. The histone deacetylase (HDAC) expression and the transcription factor nuclear factor kappa (NF-kB) were also inhibited at the same doses. In conclusion, the FJNB inhibitory actions on iNOS, COX-2, TNF-α, HDAC, and NF-kB could be involved with the drug anti-inflammatory activity.

Highlights

  • IntroductionH. drasticus latex, when added to water, is popularly known as ‘‘janaguba milk’’ and became largely used in folk medicine for the treatment of neoplasias, after medical reports of its efficacy for lung and lymphatic cancers in the 1970s

  • Himatanthus drasticus (Mart.) Plumel (Apocynaceae), known as ‘‘Janaguba’’, is a lactifer species largely distributed in several Brazilian regions, mainly in the Cariri region (Northeast Brazil) where it can be found in the ‘‘Chapada do Araripe’’ (Araripe Plateau), located in the Southern region of the State of Ceará.H. drasticus latex, when added to water, is popularly known as ‘‘janaguba milk’’ and became largely used in folk medicine for the treatment of neoplasias, after medical reports of its efficacy for lung and lymphatic cancers in the 1970s

  • We showed that FJNB significantly reduced TNFalpha immunostaining, compared with the control group

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Summary

Introduction

H. drasticus latex, when added to water, is popularly known as ‘‘janaguba milk’’ and became largely used in folk medicine for the treatment of neoplasias, after medical reports of its efficacy for lung and lymphatic cancers in the 1970s. The pharmacological potential of the species has been demonstrated in different in vivo and in vitro pre-clinical studies, pointing to the presence of anti-inflammatory, antinociceptive, antitumor, and gastroprotective actions in the latex, bark, and leaves [4,5]. The study by Lucetti et al [6] attributed these effects to the triterpene lupeol acetate, isolated from the latex, others described these effects in the protein fraction obtained from the latex mixture with water (janaguba milk) which, is devoid of lupeol

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