Abstract

Aristolochia trilobata, popularly known as “mil-homens,” is widely used for treatment of stomach aches, colic, asthma, pulmonary diseases, diabetes, and skin affection. We evaluated the antinociceptive and anti-inflammatory activities of the essential oil (EO) and the main constituent, 6-methyl-5-hepten-2-yl acetate (sulcatyl acetate, SA). EO and SA (1, 10, and 100 mg/kg, p.o.) were evaluated using chemical (formalin-induced licking) and thermal (hot-plate) models of nociception or inflammation (carrageenan-induced cell migration into the subcutaneous air pouch, SAP). The mechanism of antinociceptive activity was evaluated using opioid, cholinergic receptor antagonists (naloxone and atropine), or nitric oxide synthase inhibitor (L-NAME). EO and SA presented a central antinociceptive effect (the hot-plate model). In formalin-induced licking response, higher doses of EO and SA also reduced 1st and 2nd phases. None of the antagonists and enzyme inhibitor reversed antinociceptive effects. EO and SA reduced the leukocyte migration into the SAP, and the cytokines tumor necrosis factor and interleukin-1 (TNF-α and IL-1β, respectively) produced in the exudate. Our results are indicative that EO and SA present peripheral and central antinociceptive and anti-inflammatory effects.

Highlights

  • Inflammation and pain continue to be major problems in individuals

  • Supernatants from the exudates collected from the subcutaneous air pouch (SAP) were used to measure the levels of the cytokines tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) by enzyme-linked immunosorbent assay (ELISA) using the protocol supplied by the manufacturer (B&D, Franklin Lakes, NJ, USA)

  • Besides evaluating the effects in the formalin-induced paw licking, we used the thermal model of nociception, the hot-plate, and searched the mechanism of action of essential oil (EO) and sulcatyl acetate (SA) using three different antagonists. In another group of assays, we studied the anti-inflammatory effect of EO and SA in their capacity to inhibit the leukocyte migration into the subcutaneous air pouch induced by carrageenan and production of some inflammatory mediators

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Summary

Introduction

Inflammation and pain continue to be major problems in individuals. Both of them are a normal response of the body against invasion and/or damage. Inflammation can develop in response to an invasion by a microorganism or by physical damage and is a critical protective action to injury or infection This phenomenon presents the five cardinal signs (i.e., redness, heat, swelling, pain, and loss of function) [1]. Drugs used to treat the symptoms can be the non-steroidal anti-inflammatory drugs (NSAIDs) and/or opioids ( to pain treatment). Both groups present a large variety of side effects. (Aristolochiaceae), popularly known as “mil-homens”, is widely used in folk medicine and is an important medicinal plant [3,4] Conditions such as stomach ache, colic, poisoning, asthma, pulmonary diseases, diabetes, and skin affections have been treated with different species from Aristolochia genus [5,6]. We tried to identify the mechanism by which A. trilobata presents its effect

Animals
Plant Material
Drugs and Treatments
Formalin-Induced Licking Behavior
Cell Culture
Cell Viability Assay
2.10. Quantification of TNF-α and IL-1β
2.11. Nitrate and Nitrite Measurement
2.12. Detection of Enzymes Expression
2.13. Statistical Analysis
Mechanism of Antinociceptive
Anti-Inflammatory
Injection
Cytokine Production
Discussion
Conclusions
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