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. 2019 Apr;12(2):53-59.
doi: 10.14740/gr1142. Epub 2019 Apr 7.

The Flavone Luteolin, an Endocrine Disruptor, Relaxed Male Guinea Pig Gallbladder Strips

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Free PMC article

The Flavone Luteolin, an Endocrine Disruptor, Relaxed Male Guinea Pig Gallbladder Strips

Loren Kline. Gastroenterology Res. .
Free PMC article

Abstract

Background: Luteolin (3',4',5,7-tetrahydroxyflavone) is a flavone with a yellow crystalline appearance present in numerous plants such as broccoli, green chili, and carrot. Luteolin is considered to be an endocrine disruptor with potent estrogen agonist activity and potent progesterone antagonist activity. Luteolin has effects on smooth muscle. Luteolin relaxed guinea pig trachea smooth muscle as it inhibited both phosphodiesterase and reduced intracellular Ca2+. Luteolin also caused vasorelaxation in rat thoracic aorta smooth muscle by inhibiting intracellular Ca2+ release, inhibition of sarcolemmal Ca2+ channels, and activation of K+ channels. Luteolin or its glycosides from artichoke extracts may have an ameliorating effect on irritable bowel syndrome. The purpose of this study was to determine if luteolin had an effect on gallbladder motility.

Methods: An in vitro pharmacologic technique was utilized. Either cholecystokinin octapeptide (CCK) or KCl were used to induce tension in male guinea pig gallbladder strips maintained in Sawyer-Bartlestone chambers. Luteolin relaxed either the CCK- or KCl-induced tension in a concentration dependent manner. Various blockers were added to the chambers to determine which second messenger system(s) mediated the observed relaxation. Paired t-tests were used for statistical analysis. Differences between mean values of P < 0.05 were considered significant.

Results: Treatment of the gallbladder strips with luteolin prior to either KCl or CCK significantly (P < 0.001) decreased the amount of either KCl- or cholecystokinin-induced tension. The 2-aminoethoxydiphenylborane was used to ascertain if the release of intracellular Ca2+ mediated the luteolin-induced relaxation. It significantly (P < 0.001) decreased the amount of luteolin-induced relaxation. To ascertain if PKA mediated the luteolin-induced relaxation, PKA inhibitor 14-22 amide myristolated was used. It significantly (P < 0.01) reduced the amount of luteolin-induced relaxation. Neither KT5823, NG-methyl-L-arginine acetate salt, genistein, tetraethylammonium, nor fulvestrant had a significant effect. To ascertain if PKC mediated the luteolin-induced relaxation, the PKC inhibitors bisindolymaleimide IV and chelerythrine Cl- were used together. They had no significant effect.

Conclusions: Luteolin relaxed cholecystokinin- or KCl-induced tension by blocking extracellular Ca2+ entry as well as intracellular Ca2+ release. In addition, the actions of PKA are also involved in mediating the luteolin effect.

Keywords: Calcium; Flavone; Gallbladder; Guinea pig; Luteolin; PKA; Smooth muscle.

Figures

Figure 1
Figure 1
Effect of luteolin on CCK-induced tension (a). A data trace showing the relaxation caused by luteolin on CCK-induced tension in a male guinea pig gallbladder strip. Arrow indicates when CCK was added to the chamber (b). Luteolin was used to relax the CCK- or KCl-induced tension. The responses are concentration-dependent. Values are means ± SE.
Figure 2
Figure 2
The effect of adding luteolin (10 µM) prior to CCK or KCl. The luteolin significantly (P < 0.001) decreased the amount of CCK-induced tension. A similar result (P < 0.001) was observed when luteolin was added to the chambers prior to KCl. Values are means ± SE.
Figure 3
Figure 3
TEA (100 µM), a non-specific blocker of K+ channels, had no significant effect on luteolin-induced relaxation. The PKA blocker, PKA-IM (180 nM), significantly (P < 0.01) decreased the amount of luteolin-induced relaxation. The nitric oxide synthase blocker L-NAME (20 µM) had no significant effect on the amount of luteolin-induced relaxation. Values are means ± SE.
Figure 4
Figure 4
The effect of the PKG blocker KT5823 (585 nM) had no significant effect on the amount of luteolin-induced relaxation. Genistein (10 µM), a tyrosine kinase inhibitor, had no significant effect on the amount of luteolin-induced relaxation. The use of 2-APB (125 µM) significantly (P < 0.001) decreased the amount of luteolin-induced relaxation. Values are means ± SE.
Figure 5
Figure 5
The use of the PKC blockers BIM (0.5 µM) and chelerythrine Cl- (5.0 µM), fulvestrant (10 µM), or charybdotoxin (5 nM) had no significant effect on the amount of luteolin-induced relaxation. Values are means ± SE.

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References

    1. Lopez-Lazaro M. Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem. 2009;9(1):31–59. doi: 10.2174/138955709787001712. - DOI - PubMed
    1. Miean KH, Mohamed S. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem. 2001;49(6):3106–3112. doi: 10.1021/jf000892m. - DOI - PubMed
    1. Eyre H, Kahn R, Robertson RM, Clark NG, Doyle C, Hong Y, Gansler T. et al. Preventing cancer, cardiovascular disease, and diabetes: a common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association. Stroke. 2004;35(8):1999–2010. doi: 10.1161/01.STR.0000133321.00456.00. - DOI - PubMed
    1. Basu A, Das AS, Majumder M, Mukhopadhyay R. Antiatherogenic roles of dietary flavonoids chrysin, quercetin, and luteolin. J Cardiovasc Pharmacol. 2016;68(1):89–96. doi: 10.1097/FJC.0000000000000380. - DOI - PubMed
    1. Rice-Evans C. Flavonoid antioxidants. Curr Med Chem. 2001;8(7):797–807. doi: 10.2174/0929867013373011. - DOI - PubMed

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