Korean J Physiol Pharmacol.  2018 Jul;22(4):391-398. 10.4196/kjpp.2018.22.4.391.

Anti-inflammatory and utero-relaxant effect of α-bisabolol on the pregnant human uterus

• Muñoz-Pérez VM
• Ortiz MI
• Ponce-Monter HA
• Monter-Pérez V
• Barragán-Ramírez G

• KMID: 2414263
• DOI: http://doi.org/10.4196/kjpp.2018.22.4.391

Abstract

The aim of this study was to evaluate the in vitro anti-inflammatory and utero-relaxant effect of α-bisabolol on the pregnant human myometrium. Samples from the pregnant human myometrium were used in functional tests to evaluate the inhibitory effect of α-bisabolol (560, 860, 1,200 and 1,860 µM) on spontaneous myometrial contractions. The intracellular cyclic adenosine monophosphate (cAMP) levels generated in response to α-bisabolol in human myometrial homogenates were measured by ELISA. The anti-inflammatory effect of α-bisabolol was determined through the measurement of two pro-inflammatory cytokines, tumor necrosis factor-α (TNFα) and interleukin (IL)-1β, and the anti-inflammatory cytokine IL-10, in pregnant human myometrial explants stimulated with lipopolysaccharide (LPS). Forskolin was used as a positive control to evaluate the cAMP and cytokine levels. α-Bisabolol was found to induce a significant inhibition of spontaneous myometrial contractions at the highest concentration level (p < 0.05). α-Bisabolol caused a concentration-dependent decrease in myometrial cAMP levels (p < 0.05) and a concentration-dependent decrease in LPS-induced TNFα and IL-1β production, while IL-10 production did not increase significantly (p>0.05). The anti-inflammatory and utero-relaxant effects induced by α-bisabolol were not associated with an increase in cAMP levels in pregnant human myometrial samples. These properties place α-bisabolol as a potentially safe and effective adjuvant agent in cases of preterm birth, an area of pharmacological treatment that requires urgent improvement.

Keyword

α-bisabolol; cAMP; Immunomodulation; Inflammation; Preterm labor

MeSH Terms

Adenosine Monophosphate
Animals
Colforsin
Cytokines
Enzyme-Linked Immunosorbent Assay
Female
Humans*
Immunomodulation
In Vitro Techniques
Inflammation
Interleukin-10
Interleukins
Mice
Myometrium
Necrosis
Obstetric Labor, Premature
Pregnancy
Premature Birth
Uterine Contraction
Uterus*
Adenosine Monophosphate
Colforsin
Cytokines
Interleukin-10
Interleukins

Figure

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  Fig. 1 Inhibitory effect of α-bisabolol on spontaneous contractions.(A) Graphic representation of the effect of increasing concentrations of α-bisabolol on strips taken from the pregnant human myometrium. Each column represent the mean of the results of 5 experiments (n=5) conducted on α-bisabolol and the control (DMSO), while the vertical bars indicate the standard error of the mean (±SEM). (B) Typical recording of spontaneous uterine contractions inhibited by α-bisabolol in a concentration-dependent manner. Difference vs. basal; Difference vs. α-bisabolol 1,860 µM; *p<0.05.

• 

  Fig. 2 Intracellular cAMP levels induced by α-bisabolol and forskolin in the pregnant human myometrium.The different cAMP-levels induced both by α-bisabolol alone and combined with forskolin (10 µM) were obtained at concentrations of 560, 860 and 1,200 µM. Each column represents the mean of the results of 4 experiments (n=4) conducted on α-bisabolol and forskolin, both alone and combined, respectively. The vertical bars indicate the standard error of the mean (±SEM). †Difference vs. Basal; ‡Difference vs. Forskolin (FSK); §Difference vs. α-bisabolol 560+FSK, p<0.05.

• 

  Fig. 3 Effects of α-bisabolol and forskolin on the secretion of TNFα induced by LPS in the pregnant human myometrium.Explants were cultured both with and without LPS (10 µg/ml), in the presence of solely α-bisabolol at 560, 860 and 1,200 µM, and combined with FSK (10 µM) for 24 h. Control experiments, both basal and DMSO, were run without the addition of LPS or any other compound. Each column represents the mean of the results of 4 experiments (n=4) conducted on both compounds tested, while the vertical bars indicate the standard error of the mean (±SEM). †Difference vs. Basal; ‡Difference vs. LPS (10 µg/ml); §Difference vs. LPS+FSK, p<0.05.

• 

  Fig. 4 Effects of α-bisabolol and forskolin on the secretion of IL-1β induced by LPS in the pregnant human myometrium.Explants were cultured both without and with LPS (10 µg/ml) and in the presence of solely α-bisabolol at 560, 860 and 1,200 µM and combined with FSK (10 µM) for 24 h. Control experiments, both basal and DMSO, were run without the addition of LPS, or any other compound. Each column represents the mean of the results of 4 experiments (n=4) conducted on both compounds tested, while the vertical bars indicate the standard error of the mean (±SEM). †Difference vs. Basal; ‡Difference vs. LPS (10 µg/ml); §Difference vs. LPS+FSK, p<0.05.

• 

  Fig. 5 Effects of α-bisabolol and forskolin on the secretion of IL-10 induced by LPS in the pregnant human myometrium.Explants were cultured both with and without LPS (10 µg/ml) and in presence of solely α-bisabolol using the concentration of 860 µM both on its own and combined with FSK (10 µM) for 24 h. Control experiments, both basal and DMSO, were run without the addition of LPS or any other compound. Each column represents the mean of the results of 4 experiments (n=4) conducted on both compounds tested, while the vertical bars indicate the standard error of the mean (±SEM). †Difference vs. Basal; ‡Difference vs. LPS (10 µg/ml); §Difference vs. LPS+FSK, p<0.05.

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