Long lasting preventive effects of piperlongumine and a Piper longum extract against stress triggered pathologies in mice

Abstract

Aim: To compare doxycycline (DOX) such as oral efficacies of piperlongumine (PL) and a Piper longum fruits extract (PLE) as stress resistance inducers.

Materials and methods: Efficacies of oral pretreatments with 5 mg/kg PL or PLE or of 50 mg/kg DOX for 10 consecutive days against stress resistance were compared. Mice in treated groups were subjected to a stress induced hyperthermia on the 1(st), 5(th), 7(th), and 10(th)day. Treated mice were then subjected to tail suspension test on the 11(th)day. Alteration in body weights, core temperatures, and gastric ulcers triggered by occasional exposures to foot shocks were determined.

Results: DOX like long-lasting protective effects of PL and PLE against gradual alterations in body weights, basal temperatures and transient hyperthermic responses triggered by foot shocks during the post-treatment days were observed. Altered responses of stressed mice in tail suspension test observed 1 day after the last foot-shock exposures and gastric ulcers and other pathologies quantified 1 day after the test were also suppressed in PL or PLE or DOX pretreated groups.

Conclusion: PL and crude PLE are DOX like long-acting desensitizers of stress triggered co-morbidities. Reported observations add further experimental evidences justifying traditionally known medicinal uses of P. longum and other plants of the Piperaceae family, and reveal that PL is also another very long acting and orally active inducer of stress resistance. Efforts to confirm stress preventive potentials of low dose plant-derived products enriched in PL or piperine like amide alkaloids in volunteers and patients can be warranted.

Keywords: Foot-shock stress; Piper longum; gastric ulcer; hyperthermia; piperine; piperlongumine; prophylaxes.

Figure 1

Structure of (a) Piperine and (b) Piperlongumine

Figure 2

Summary of the experimental methods used

Figure 3

Effect of occasional stress on body weight of male mice treated with piperlongumine and Piper longum fruits extract on day 1-10 (a) and day 10-22 (b) of experiment. Abbreviations: PL: Piperlongumine, PLE: Piper longum fruits extract, DOX: Doxycycline, CMC: Carboxymethyl cellulose suspension and REF: Reference group. Values are mean ± standard error of mean (n = 6). * denotes statistically significant difference (two-way Analysis of Variance followed by Bonferroni post-hoc test) relative to CON + CMC group (*P < 0.05).

Figure 4

Effect of occasional stress on basal rectal temperatures of male mice treated with piperlongumine and Piper longum fruits extract on day 1-10 (a) and day 10-22 (b) of experiment. Values are mean ± standard error of mean (n = 6). *denotes statistically significant difference (two-way Analysis of Variance followed by Bonferroni post-hoc test) relative to CON + carboxymethyl cellulose group (*P < 0.05).

Figure 5

Effect of stress on ratio of body weight and basal rectal temperature of male mice treated with and Piper longum fruits extract on day 1-10 (a) and day 10-22 (b) of experiment. Values are mean ± standard error of mean (n = 6). *denotes statistically significant difference (two-way ANOVA followed by Bonferroni post-hoc test) relative to CON + carboxymethyl cellulose group (*P < 0.05). ¥denotes statistically significant difference (two-way ANOVA followed by Bonferroni post-hoc test) relative to reference (¥P < 0.05)

Figure 6

Stress induced hyperthermia of male mice treated with piperlongumine and Piper longum fruits extract. Values are mean ± standard error of mean (n = 6). *denotes statistically significant difference (two-way Analysis of Variance [ANOVA] followed by Bonferroni post-hoc test) relative to CON + carboxymethyl cellulose group (*P < 0.05). ¥denotes statistically significant difference (two-way ANOVA followed by Bonferroni post-hoc test) relative to Reference (¥P < 0.05)

Figure 7

Effect of piperlongumine and Piper longum fruits extract on tail suspension test in male mice. Abbreviations: Values are mean ± standard error of mean (n = 6). * denotes statistically significant difference (One-way Analysis of Variance [ANOVA] followed by Student’s t-test) relative to CON + carboxymethyl cellulose group (*P < 0.05). ¥denotes statistically significant difference (One-way ANOVA followed by Student’s t-test) relative to REF (¥P < 0.05)