1.Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone.
Charlotte DETREMMERIE ; Paul M VANHOUTTE ; Susan LEUNG
Acta Pharmaceutica Sinica B 2017;7(4):401-408
The natural compound thymoquinone, extracted from(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 3',5'-cyclic monophosphate (cyclic IMP) rather than guanosine 3',5'-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.
2.Optimizing 5-aminosalicylate for moderate ulcerative colitis: expert recommendations from the Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition
Filiz AKYÜZ ; Yoon Kyo AN ; Jakob BEGUN ; Satimai ANIWAN ; Huu Hoang BUI ; Webber CHAN ; Chang Hwan CHOI ; Nazeer CHOPDAT ; Susan J CONNOR ; Devendra DESAI ; Emma FLANAGAN ; Taku KOBAYASHI ; Allen Yu-Hung LAI ; Rupert W LEONG ; Alex Hwong-Ruey LEOW ; Wai Keung LEUNG ; Julajak LIMSRIVILAI ; Virly Nanda MUZELLINA ; Kiran PEDDI ; Zhihua RAN ; Shu Chen WEI ; Jose SOLLANO ; Michelle Mui Hian TEO ; Kaichun WU ; Byong Duk YE ; Choon Jin OOI
Intestinal Research 2025;23(1):37-55
The lack of clear definition and classification for “moderate ulcerative colitis (UC)” creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.
3.Optimizing 5-aminosalicylate for moderate ulcerative colitis: expert recommendations from the Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition
Filiz AKYÜZ ; Yoon Kyo AN ; Jakob BEGUN ; Satimai ANIWAN ; Huu Hoang BUI ; Webber CHAN ; Chang Hwan CHOI ; Nazeer CHOPDAT ; Susan J CONNOR ; Devendra DESAI ; Emma FLANAGAN ; Taku KOBAYASHI ; Allen Yu-Hung LAI ; Rupert W LEONG ; Alex Hwong-Ruey LEOW ; Wai Keung LEUNG ; Julajak LIMSRIVILAI ; Virly Nanda MUZELLINA ; Kiran PEDDI ; Zhihua RAN ; Shu Chen WEI ; Jose SOLLANO ; Michelle Mui Hian TEO ; Kaichun WU ; Byong Duk YE ; Choon Jin OOI
Intestinal Research 2025;23(1):37-55
The lack of clear definition and classification for “moderate ulcerative colitis (UC)” creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.
4.Optimizing 5-aminosalicylate for moderate ulcerative colitis: expert recommendations from the Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition
Filiz AKYÜZ ; Yoon Kyo AN ; Jakob BEGUN ; Satimai ANIWAN ; Huu Hoang BUI ; Webber CHAN ; Chang Hwan CHOI ; Nazeer CHOPDAT ; Susan J CONNOR ; Devendra DESAI ; Emma FLANAGAN ; Taku KOBAYASHI ; Allen Yu-Hung LAI ; Rupert W LEONG ; Alex Hwong-Ruey LEOW ; Wai Keung LEUNG ; Julajak LIMSRIVILAI ; Virly Nanda MUZELLINA ; Kiran PEDDI ; Zhihua RAN ; Shu Chen WEI ; Jose SOLLANO ; Michelle Mui Hian TEO ; Kaichun WU ; Byong Duk YE ; Choon Jin OOI
Intestinal Research 2025;23(1):37-55
The lack of clear definition and classification for “moderate ulcerative colitis (UC)” creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.