Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone
The natural compound thymoquinone, extracted from Nigella sativa (black cumin), is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation o...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-07-01
|
| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383517302290 |
| _version_ | 1828807064423497728 |
|---|---|
| author | Charlotte Detremmerie Paul M. Vanhoutte Susan Leung |
| author_facet | Charlotte Detremmerie Paul M. Vanhoutte Susan Leung |
| author_sort | Charlotte Detremmerie |
| collection | DOAJ |
| description | The natural compound thymoquinone, extracted from Nigella sativa (black cumin), is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously, thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase (sGC) producing inosine 3ʹ,5ʹ-cyclic monophosphate (cyclic IMP) rather than guanosine 3ʹ,5ʹ-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic IMP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC. |
| first_indexed | 2024-12-12T08:19:49Z |
| format | Article |
| id | doaj.art-301ee618163a463a87a7d4e799ef10fe |
| institution | Directory Open Access Journal |
| issn | 2211-3835 2211-3843 |
| language | English |
| last_indexed | 2024-12-12T08:19:49Z |
| publishDate | 2017-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-301ee618163a463a87a7d4e799ef10fe2022-12-22T00:31:26ZengElsevierActa Pharmaceutica Sinica B2211-38352211-38432017-07-017440140810.1016/j.apsb.2017.06.003Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinoneCharlotte DetremmeriePaul M. VanhoutteSusan LeungThe natural compound thymoquinone, extracted from Nigella sativa (black cumin), is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously, thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase (sGC) producing inosine 3ʹ,5ʹ-cyclic monophosphate (cyclic IMP) rather than guanosine 3ʹ,5ʹ-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic IMP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.http://www.sciencedirect.com/science/article/pii/S2211383517302290ThymoquinoneEndothelium-dependentcontractionNitric oxideSoluble guanylyl cyclaseCyclic IMPNADPH:quinone oxidoreductase |
| spellingShingle | Charlotte Detremmerie Paul M. Vanhoutte Susan Leung Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone Acta Pharmaceutica Sinica B Thymoquinone Endothelium-dependentcontraction Nitric oxide Soluble guanylyl cyclase Cyclic IMP NADPH:quinone oxidoreductase |
| title | Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone |
| title_full | Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone |
| title_fullStr | Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone |
| title_full_unstemmed | Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone |
| title_short | Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone |
| title_sort | biased activity of soluble guanylyl cyclase the janus face of thymoquinone |
| topic | Thymoquinone Endothelium-dependentcontraction Nitric oxide Soluble guanylyl cyclase Cyclic IMP NADPH:quinone oxidoreductase |
| url | http://www.sciencedirect.com/science/article/pii/S2211383517302290 |
| work_keys_str_mv | AT charlottedetremmerie biasedactivityofsolubleguanylylcyclasethejanusfaceofthymoquinone AT paulmvanhoutte biasedactivityofsolubleguanylylcyclasethejanusfaceofthymoquinone AT susanleung biasedactivityofsolubleguanylylcyclasethejanusfaceofthymoquinone |