Antiarthritic and Antinociceptive Properties of Ylang-Ylang (Cananga odorata) Essential Oil in Experimental Models

Abstract

The aim of this study was to evaluate the effect of ylang-ylang (Cananga odorata) essential oil (YEO) on models of experimental arthritis, persistent inflammation, and nociception in mice. YEO treatment at doses of 100 and 200 mg/kg reduced the infiltration of leukocytes into the joint cavities of mice submitted to zymosan-induced arthritis 6 h and 7 days after arthritis induction. At these doses, YEO treatment reduced the formation of joint edema 4 and 6 h after arthritis induction, and at a dose of 200 mg/kg, YEO treatment reduced mechanical hyperalgesia 3 and 4 h after arthritis induction. At the dose of 200 mg/kg, YEO treatment reduced interleukin-6 (IL-6) levels and cartilage destruction in the zymosan-induced arthritis model, and reduced edema formation and mechanical hyperalgesia in the model of persistent inflammation (21 days) induced by complete Freund's adjuvant (CFA) in mice. YEO treatment at a dose of 200 mg/kg reduced the nociceptive response in experimental models of nociception induced by acetic acid and formalin. The YEO treatment reduced inflammatory parameters in the experimental arthritis model, and presented antiarthritic, anti-hyperalgesic, antinociceptive, and anti-inflammatory properties.

Keywords: arthritis; essential oil; natural products; persistent inflammation; ylang-ylang.

Figure 1

Effect of YEO treatment on mechanical hyperalgesia in Swiss mice submitted to zymosan-induced arthritis. This figure shows the values observed 3 h (a) and 4 h (b) after arthritis induction in the control (vehicle, p.o.), YEO (50, 100, and 200 mg/kg, p.o.), and dexamethasone (1 mg/kg, p.o.) groups. Results are expressed as the mean ± SEM. ^# p < 0.05 compared to the saline group (vehicle); * p < 0.05 compared to the control group (ANOVA, Newman–Keuls test).

Figure 2

Effect of YEO treatment on edema formation in Swiss mice submitted to zymosan-induced arthritis. This figure shows the degree of knee edema formation at 4 (a) and 6 (b) hours after arthritis induction in the control (vehicle, p.o.), YEO (50, 100, and 200 mg/kg, p.o.), and dexamethasone (1 mg/kg, p.o.) groups. Results are expressed as the mean ± SEM. ^# p < 0.05 compared to the saline group (vehicle); * p < 0.05 compared to the control group (ANOVA, Newman–Keuls test).

Figure 3

Effect of YEO treatment on migrated leukocyte number in the knee-joint cavities of Swiss mice 6 h (a) and 7 days (b) after zymosan-induced arthritis in the control (vehicle, p.o.), YEO (50, 100, and 200 mg/kg, p.o.), and dexamethasone (1 mg/kg, p.o.) groups. ^# p < 0.05 compared to saline treatment (vehicle); * p < 0.05 compared to the control group (ANOVA, Newman–Keul test).

Figure 4

Effect of YEO treatment on IL-6 levels in the synovial fluid of Swiss mice 6 h after zymosan-induced arthritis in the control (vehicle, p.o.), YEO (200 mg/kg, p.o.), and dexamethasone (1 mg/kg, p.o.) groups. ^# p < 0.05 compared to saline treatment (vehicle); * p < 0.05 compared to the control group (ANOVA, Newman–Keul test).

Figure 5

Cartilage histopathology degradation assessment in the knee-joint cavities of Swiss mice 7 days after zymosan-induced arthritis: results of saline treatment (vehicle) (a); control treatment (vehicle, p.o.), showing fibrillation (arrows) (b); YEO treatment (200 mg/kg, p.o.) (c); and dexamethasone treatment (1 mg/kg, p.o.) (d). These images demonstrate that discontinuity on the surface of the synovial membrane, fibrillation (arrows), disorientation of the chondrocyte columns, cell death, proliferation (clustering), and hypertrophy were observed in the arthritic animals when compared to the animals that received only saline injections.

Figure 6

Effects of chronic oral administration of YEO (200 mg/kg) on CFA-induced mechanical hyperalgesia (a) and edema formation (b) 6, 11, 16, and 21 days after CFA injection. The animals received a single oral administration of YEO (200 mg/kg) once a day for 21 days in the CFA model. Each bar represents the mean ± SEM of 4 animals. ** p < 0.01, *** p < 0.001, compared with the control group. A two-way ANOVA was performed, followed by the Newman–Keuls test.

Figure 7

Effect of YEO treatment on acetic acid-induced abdominal writhing. Animals were pretreated 60 min before the challenge, p.o., with the YEO (200 mg/kg), and the animals in the control group received water or indomethacin (n = 5–7 animals/group). Mice were stimulated with an injection via i.p. of 0.6% acetic acid (10 mL/kg), and the number of writhing contortions was recorded over 30 min. Results are expressed as the mean ± SEM. ^# p < 0.05 compared to saline treatment (vehicle); * p < 0.05 compared to the control group (ANOVA, Newman–Keul test).

Figure 8

Effect of YEO treatment (200 mg/kg) on formalin-induced paw-licking time. Animals were pretreated 60 min before the challenge, p.o., with YEO (200 mg/kg), and the animals in the control group received water, indomethacin, or morphine. Paw-licking time was timed in the 1st phase (0–5 min) (a) and the 2nd phase (15–30 min) (b) after intraplantar injections of 1.2% formalin in the hind paws of the mice. Results are expressed as the mean ± SEM. ^# p < 0.05 compared to saline treatment (vehicle); * p < 0.05 compared to the control group (ANOVA, Newman–Keuls test).