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

Munoz-Perez, Victor Manuel; Ortiz, Mario I.; Ponce-Monter, Hector A.; Monter-Perez, Vicente; Barragan-Ramirez, Guillermo

doi:10.4196/kjpp.2018.22.4.391

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

The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, v.22 no.4, 2018년, pp.391 - 398

Munoz-Perez, Victor Manuel (Area Academica de Medicina del Instituto de Ciencias de la Salud. Universidad Autonoma del Estado de Hidalgo) , Ortiz, Mario I. (Area Academica de Medicina del Instituto de Ciencias de la Salud. Universidad Autonoma del Estado de Hidalgo) , Ponce-Monter, Hector A. (Area Academica de Medicina del Instituto de Ciencias de la Salud. Universidad Autonoma del Estado de Hidalgo) , Monter-Perez, Vicente (Hospital General de los SSH) , Barragan-Ramirez, Guillermo (Hospital General de los SSH)

Abstract ▼ AI-Helper

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

주제어

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문제 정의

One of the aims of this research was to study the relaxation effects of α-bisabolol on spontaneous contractions of the pregnant human myometrium.
The authors thank Shamayra Sauz Hernández and Karina Reséndiz Sánchez from the SSH General Hospital, Pachuca, Hidalgo, Mexico, for their support and collaboration in the gynecological field.
Therefore, the aim of the present study was to evaluate and corroborate the relaxant and anti-inflammatory effects of α-bisabolol on the pregnant human uterus.

제안 방법

Data for the effect of the drugs of interest on spontaneous uterine contractions were subjected to a concentration-response column analysis performed using Sigma Plot version 10 software (Systat Software Inc., San Jose, CA, USA) in order to obtain values for inhibitory concentration 50 (IC₅₀) (a drug concentration that produces 50% of the maximum inhibitory effect), and E_max, a maximum inhibitory response that can be produced by the highest concentration of the tested compound. Data are expressed as the means±SEM taken from determinations for each concentration (n=5).
In order to confirm whether the utero-relaxant effect induced by α-bisabolol was caused by intracellular cAMP levels, this research measured the production of cAMP in the pregnant human myometrium in the presence of α-bisabolol, using the specific AC activator forskolin as a positive control [26].
In order to corroborate such properties, this study first carried out research on the relaxing effect of α-bisabolol on spontaneous contractions in the pregnant human myometrium.
The changes in the contractile activity of the isometric tension were recorded using a Grass FT03 tension transducer coupled to an RPS-312 RM model polygraph (Grass Telefactor, RI, USA). The data were analyzed using PolyVIEW software, version 2.5, while the uterine contractions (integral activity) were measured using the area under the curve (AUC) defined by the graphic isometric record over a 20 min period after stabilization. The inhibitory effect of α-bisabolol on spontaneous uterine contractions was expressed as follows:

데이터처리

Data are expressed as the means±SEM taken from determinations for each concentration (n=5). The IC₅₀ and E_max differences among the compounds were determined by a one-way ANOVA test followed by a posthoc Student-Newman-Keuls test using Sigma Stat software, version 3.1 (Systat Software Inc., San Jose, CA, USA). In all cases, p<0.

성능/효과

4) (p<0.05), when α–bisabolol (560-1,200 μM) was combined with LPS and forskolin, the TNF-α and IL-1β levels decreased in a significant concentration-dependent manner (p<0.05).
A statistically significant difference was found between the basal value obtained from DMSO and the values for the increasing concentrations of α-bisabolol, p<0.05.
The results of this study show that α-bisabolol promotes an interesting anti-inflammatory effect on the pregnant human myometrium, an effect which was associated with the inhibition of the production of TNF-α and IL-1β, and with the increase of the anti-inflammatory cytokine IL-10 (Figs. 3-5).
The results of this study show that the immunomodulatory and anti-inflammatory effects induced by α-bisabolol were consistent with other reports, which demonstrated the ability of α-bisabolol to inhibit the release of the proinflammatory cytokines induced with LPS in mice and human dendritic cells [43,44].
These data are consistent with the results obtained by this research, which show that α-bisabolol can inhibit spontaneous contractions in the pregnant human uterus, an effect which could also be related to the blockade of the calcium channels, as reported in the studies mentioned above.

후속연구

Further studies are required to evaluate, in detail, the α-bisabolol mechanism of action involved in the blockade of voltage-gated calcium channels in the uterine smooth muscle.
However, further studies are required to determine how α-bisabolol induces the inhibition of the uterine contraction.

참고문헌 (46)

1 Kemp MW Saito M Newnham JP Nitsos I Okamura K Kallapur SG Preterm birth, infection, and inflammation advances from the study of animal models Reprod Sci 2010 17 619 628 20581349

상세보기
2 Burdet J Rubio AP Salazar AI Ribeiro ML Ibarra C Franchi AM Inflammation, infection and preterm birth Curr Pharm Des 2014 20 4741 4748 24588830

상세보기
3 Munoz-Perez VM Fernandez-Martinez E Ponce-Monter H Ortiz MI Relaxant and anti-inflammatory effect of two thalidomide analogs as PDE-4 inhibitors in pregnant rat uterus Korean J Physiol Pharmacol 2017 21 429 437 28706457
4 Hubinont C Debieve F Prevention of preterm labour: 2011 update on tocolysis J Pregnancy 2011 2011 941057 22175022

상세보기
5 de Heus R Mol BW Erwich JJ van Geijn HP Gyselaers WJ Hanssens M Harmark L van Holsbeke CD Duvekot JJ Schobben FF Wolf H Visser GH Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study BMJ 2009 338 b744 19264820

상세보기
6 Abitayeh G Tsatsaris V Goffinet F Cabrol D New tocolytic agents Eur Clinics Obstet Gynecol 2005 1 29 35
7 Agrawal V Hirsch E Intrauterine infection and preterm labor Semin Fetal Neonatal Med 2012 17 12 19 21944863
8 Rocha NF Oliveira GV Araujo FY Rios ER Carvalho AM Vasconcelos LF Macedo DS Soares PM Sousa DP Sousa FC (？)-α-Bisabolol-induced gastroprotection is associated with reduction in lipid peroxidation, superoxide dismutase activity and neutrophil migration Eur J Pharm Sci 2011 44 455 461 21924353
9 de Siqueira RJ Freire WB Vasconcelos-Silva AA Fonseca-Magalhaes PA Lima FJ Brito TS Mourao LT Ribeiro RA Lahlou S Magalhaes PJ In-vitro characterization of the pharmacological effects induced by (-)-α-bisabolol in rat smooth muscle preparations Can J Physiol Pharmacol 2012 90 23 35 22171824
10 Ko SG Yin CS Du B Kim KH Herbal medicines for inflammatory diseases 2016 Mediators Inflamm 2016 2016 8270323 27847408
11 Jeon JS Kim HT Kim MG Oh MS Hong SR Yoon MH Shin HC Shim JH Afifi NA Hacımuftuolu A El-Aty AMA Simultaneous detection of glabridin, (？)-α-bisabolol, and ascorbyl tetraisopalmitate in whitening cosmetic creams using HPLC-PAD Chromatographia 2016 79 851 860
12 de Siqueira RJ Ribeiro-Filho HV Freire RS Cosker F Freire WB Vasconcelos-Silva AA Soares MA Lahlou S Magalhaes PJ (？)-α-Bisabolol inhibits preferentially electromechanical coupling on rat isolated arteries Vascul Pharmacol 2014 63 37 45 25128618
13 Fernandez-Martinez E Ponce-Monter H Soria-Jasso LE Ortiz MI Arias-Montano JA Barragan-Ramirez G Mayen-Garcia C Inhibition of uterine contractility by thalidomide analogs via phosphodiesterase-4 inhibition and calcium entry blockade Molecules 2016 21 E1332 27739411

상세보기
14 Oger S Mehats C Barnette MS Ferre F Cabrol D Leroy MJ Anti-inflammatory and utero-relaxant effects in human myometrium of new generation phosphodiesterase 4 inhibitors Biol Reprod 2004 70 458 464 14561639

상세보기
15 Kinney MV Lawn JE Howson CP Belizan J 15 Million preterm births annually: what has changed this year? Reprod Health 2012 9 28 23148557

상세보기
16 Purisch SE Gyamfi-Bannerman C Epidemiology of preterm birth Semin Perinatol 2017 41 387 391 28865982

상세보기
17 Rezaeizadeh G Hantoushzadeh S Ghiasi S Nikfar S Abdollahi M A systematic review of the uterine relaxant effect of herbal sources Curr Pharm Biotechnol 2016 17 934 948 27396394

상세보기
18 Tribe RM Regulation of human myometrial contractility during pregnancy and labour: are calcium homeostatic pathways important? Exp Physiol 2001 86 247 254 11429641

상세보기
19 Garfield RE Maner WL Physiology and electrical activity of uterine contractions Semin Cell Dev Biol 2007 18 289 295 17659954

상세보기
20 Pehlivanolu B Bayrak S Doan M A close look at the contraction and relaxation of the myometrium; the role of calcium J Turk Ger Gynecol Assoc 2013 14 230 234 24592112
21 Luckas MJ Taggart MJ Wray S Intracellular calcium stores and agonist-induced contractions in isolated human myometrium Am J Obstet Gynecol 1999 181 468 476 10454702

상세보기
22 Roberts RE Allen S Chang AP Henderson H Hobson GC Karania B Morgan KN Pek AS Raghvani K Shee CY Shikotra J Street E Abbas Z Ellis K Heer JK Alexander SP Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels Toxicol Appl Pharmacol 2013 272 797 805 23845591

상세보기
23 Sassone-Corsi P The cyclic AMP pathway Cold Spring Harb Perspect Biol 2012 4 a011148 23209152
24 Tasken K Aandahl EM Localized effects of cAMP mediated by distinct routes of protein kinase A Physiol Rev 2004 84 137 167 14715913

상세보기
25 Brenner S Prosch S Schenke-Layland K Riese U Gausmann U Platzer C cAMP-induced Interleukin-10 promoter activation depends on CCAAT/enhancer-binding protein expression and monocytic differentiation J Biol Chem 2003 278 5597 5604 12493739

상세보기
26 Insel PA Ostrom RS Forskolin as a tool for examining adenylyl cyclase expression, regulation, and G protein signaling Cell Mol Neurobiol 2003 23 305 314 12825829

상세보기
27 Choi YH Kim GY Lee HH Anti-inflammatory effects of cordycepin in lipopolysaccharide-stimulated RAW 264.7 macrophages through Toll-like receptor 4-mediated suppression of mitogen-activated protein kinases and NF-κB signaling pathways Drug Des Devel Ther 2014 8 1941 1953
28 Cha JY Jung JY Jung JY Lee JR Cho IJ Ku SK Byun SH Ahn YT Lee CW Kim SC An WG Inhibitory effects of traditional herbal formula pyungwi-san on inflammatory response in vitro and in vivo Evid Based Complement Alternat Med 2013 2013 630198 23533508

상세보기
29 Gomez-Lopez N StLouis D Lehr MA Sanchez-Rodriguez EN Arenas-Hernandez M Immune cells in term and preterm labor Cell Mol Immunol 2014 11 571 581 24954221
30 Jantan I Ahmad W Bukhari SN Plant-derived immunomodulators: an insight on their preclinical evaluation and clinical trials Front Plant Sci 2015 6 655 26379683
31 Kiemer AK Muller C Vollmar AM Inhibition of LPS-induced nitric oxide and TNF-alpha production by alpha-lipoic acid in rat Kupffer cells and in RAW 264.7 murine macrophages Immunol Cell Biol 2002 80 550 557 12406389
32 Saad B Abouatta BS Basha W Hmade A Kmail A Khasib S Said O Hypericum triquetrifolium-derived factors downregulate the production levels of LPS-induced nitric oxide and tumor necrosis factor-α in THP-1 cells Evid Based Complement Alternat Med 2011 2011 586470 18955363
33 Iyer SS Cheng G Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease Crit Rev Immunol 2012 32 23 63 22428854

상세보기
34 Saraiva M O'Garra A The regulation of IL-10 production by immune cells Nat Rev Immunol 2010 10 170 181 20154735

상세보기
35 Kelly A Lynch A Vereker E Nolan Y Queenan P Whittaker E O'Neill LA Lynch MA The anti-inflammatory cytokine, interleukin (IL)-10, blocks the inhibitory effect of IL-1 beta on long term potentiation. A role for JNK J Biol Chem 2001 276 45564 45572 11581275
36 Oger S Mehats C Dallot E Ferre F Leroy MJ Interleukin-1beta induces phosphodiesterase 4B2 expression in human myometrial cells through a prostaglandin E2- and cyclic adenosine 3′,5′-monophosphate-dependent pathway J Clin Endocrinol Metab 2002 87 5524 5531 12466348
37 D'Almeida APL Pacheco de Oliveira MT de Souza ET de Sa Coutinho D Ciambarella BT Gomes CR Terroso T Guterres SS Pohlmann AR Silva PM Martins MA Bernardi A α-Bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice Int J Nanomedicine 2017 12 4479 4491 28684908
38 Roh E Yun CY Young Yun J Park D Doo Kim N Yeon Hwang B Jung SH Park SK Kim YB Han SB Kim Y cAMP-binding site of PKA as a molecular target of bisabolangelone against melanocyte-specific hyperpigmented disorder J Invest Dermatol 2013 133 1072 1079 23254773

상세보기
39 Kim S Lee J Jung E Huh S Park JO Lee JW Byun SY Park D Mechanisms of depigmentation by alpha-bisabolol J Dermatol Sci 2008 52 219 222 18692366
40 Avni D Ernst O Philosoph A Zor T Role of CREB in modulation of TNFalpha and IL-10 expression in LPS-stimulated RAW264.7 macrophages Mol Immunol 2010 47 1396 1403 20303596
41 Wen AY Sakamoto KM Miller LS The role of the transcription factor CREB in immune function J Immunol 2010 185 6413 6419 21084670

상세보기
42 Shima E Katsube M Kato T Kitagawa M Hato F Hino M Takahashi T Fujita H Kitagawa S Calcium channel blockers suppress cytokine-induced activation of human neutrophils Am J Hypertens 2008 21 78 84 18091748

상세보기
43 Barreto RSS Quintans JSS Amarante RKL Nascimento TS Amarante RS Barreto AS Pereira EWM Duarte MC Coutinho HDM Menezes IRA Zengin G Aktumsek A Quintans-Junior LJ Evidence for the involvement of TNF-α and IL-1β in the antinociceptive and anti-inflammatory activity of Stachys lavandulifolia Vahl. (Lamiaceae) essential oil and (？)-α-bisabolol, its main compound, in mice J Ethnopharmacol 2016 191 9 18 27292196
44 Marongiu L Donini M Bovi M Perduca M Vivian F Romeo A Mariotto S Monaco HL Dusi S The inclusion into PLGA nanoparticles enables α-bisabolol to efficiently inhibit the human dendritic cell pro-inflammatory activity J Nanopart Res 2014 16 2554
45 Corpas-Lopez V Morillas-Marquez F Navarro-Moll MC Merino-Espinosa G Diaz-Saez V Martin-Sanchez J (？)-α-Bisabolol, a promising oral compound for the treatment of visceral leishmaniasis J Nat Prod 2015 78 1202 1207 26076227
46 Andersen FA Final report on the safety assessment of Bisabolol Int J Toxicol 1999 18 3 suppl 33 40

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