A Hydroethanolic Leaf Extract of Persicaria lanigera Possesses Antinociceptive Activity through Cytokine and Glutamatergic Pathways In Vivo

Abstract

Persicaria lanigera is used traditionally to treat pain. The antinociceptive properties of the hydroethanolic leaf extract of Persicaria lanigera (PLE) were evaluated in rats and mice. Mice were pretreated orally with PLE (30, 100, and 300 mg kg^-1) and evaluated for antinociceptive effects in the acetic acid-, glutamate-, and formalin-induced nociception models. Additionally, mechanical hyperalgesia models were used to evaluate PLE's influence on TNF-α- and IL-1β-induced hyperalgesia in rats. In the acetic acid-induced nociception model, 100 mg kg^-1 PLE exhibited the highest antinociceptive activity of 95.13 ± 9.52% at p < 0.0001, followed by the 300 mg kg^-1 (85.44 ± 5.75%; p < 0.0001) and then the 30 mg kg^-1 (67.95 ± 18.55%; p < 0.01), compared to morphine 3 mg kg^-1 i.p. (86.97 ± 9.52; p < 0.0001). PLE (30, 100, and 300 mg kg^-1) also showed significant (p < 0.05) antinociceptive effect in phase two of the formalin-induced nociception with % inhibitions of 66.88 ± 12.17, 75.12 ± 9.01, and 89.12 ± 4.32%, respectively, compared to 3 mg/kg morphine (97.09 ± 2.84%). Similarly, PLE (30, 100, and 300 mg kg^-1) significantly reduced pain in the glutamate-induced nociception model with % inhibitions of 79.28 ± 8.17, 90.54 ± 5.64, and 96.49 ± 1.43%, respectively, whereas ketamine (5 mg/kg i.p.) reduced nociception to be 59.94 ± 18.14%. All doses of PLE significantly reduced nociceptive scores in TNF-α- and IL-1β-induced mechanical hyperalgesia (p < 0.01). Similarly, PLE significantly inhibited bradykinin-induced nociception. The hydroethanolic extract of Persicaria lanigera has antinociceptive effects; this is the first scientific report providing evidence to validate its traditional use for the management of pain.

Figure 1

HPLC chromatogram of PLE.

Figure 2

The effect of PLE on (a) nociceptive score and (b) total nociceptive scores in acetic acid-induced writhing in mice. Data are presented as mean ± SEM. The symbols ^∗ and † indicate the significance levels compared to respective controls: ^∗∗∗∗p < 0.0001, ^∗∗∗p < 0.001 (two-way ANOVA followed by Bonferroni's post hoc test); ^††††p < 0.0001, ^††p < 0.01 (one-way ANOVA followed by Newman–Keuls post hoc test).

Figure 3

The effect of PLE on formalin-induced nociception: (a) time-course curve (TCC) for the antinociceptive activity of PLE; (b) AUC of the time-course curve. Results are presented as means ± SEM of the latency period (n = 5). ^∗p < 0.05 and ^†p < 0.05 compared to respective controls (one-way ANOVA followed by Newman–Keuls' post hoc test).

Figure 4

Effect of PLE (30, 100, and 300 mg kg⁻¹) and ketamine (5 mg kg⁻¹, i.p.) on glutamate-induced nociceptive pain: (a) the time-course curve; (b) AUC of the time-course curve. Each data represents the mean of 5 animals and the error bars indicate SEM. ^∗ and † indicate the significance levels compared to respective controls: ^∗∗∗p < 0.001 (two-way ANOVA followed by Bonferroni's post hoc test); ^†††p < 0.001, ^††p < 0.01, ^†p < 0.05 (one-way ANOVA followed by Newman–Keuls post hoc test).

Figure 5

The effect of PLE and morphine on TNF-α-induced hyperalgesia: (a) time-course curve; (b) AUCs of the time-course curve. Each point represents the mean ± SEM. Each datum represents the mean of five animals and the error bars indicate SEM. The symbols ^∗ and † indicate the significance levels compared to respective controls: ^∗∗∗∗p < 0.0001, ^∗∗p < 0.01, ^∗p < 0.05 (two-way ANOVA followed by Bonferroni's post hoc test); ^†††p < 0.001, ^††p < 0.01, ^†p < 0.05 (one-way ANOVA followed by Newman–Keuls post hoc test).

Figure 6

Effect of PLE and morphine on interleukin-1β-induced hypernociception: (a) time-course curves; (b) AUCs of the time-course curves. Data presented as mean ± SEM. The symbols ^∗ and † indicate the significance levels compared to respective controls: ^∗∗∗∗p < 0.001, ^∗∗p < 0.01, ^∗p < 0.05 (two-way ANOVA followed by Bonferroni's post hoc test); ^†††p < 0.001, ^††p < 0.01 (one-way ANOVA followed by Newman–Keuls post hoc test).

Figure 7

The effect of PLE and morphine on bradykinin-induced mechanical hyperalgesia in rats: (a) time-course curves; (b) AUCs of time-course curves. Data are presented as mean ± SEM. The symbols ^∗ and † indicate the significance levels compared to respective controls: ^∗∗∗∗p < 0.0001, ^∗∗p < 0.01 (two-way ANOVA followed by Bonferroni's post hoc test); ^††††p < 0.0001, ^††p < 0.01 (one-way ANOVA followed by Newman–Keuls post hoc test).