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Biased activity of soluble guanylyl cyclase:the Janus face of thymoquinone

Acta Pharmaceutica Sinica B 2017年第4期7卷 401-408页

作者： Charlotte Detremmerie Paul M.Vanhoutte susan leung Department of Pharmacology and Pharmacy and State Key Laboratory for Pharmaceutical Biotechnology Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina

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 endotheliumindependent 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.

关键词： Thymoquinone Endothelium-dependentcontraction Nitric oxide Soluble guanylyl cyclase Cyclic IMP NADPH:quinone oxidoreductase

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Contents of four active components in different commercial crude drugs and preparations of Danshen (Salvia miltiorrhiza)

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Acta Pharmacologica Sinica 2002年第12期23卷 110-115页

作者： susan Wai Sum leung,Yaw Loong SIOW,Ricky Ying Keung MAN Department of Pharmacology Faculty of Medicine University of Hong Kong 21 Sassoon Road Hong Kong China Department of Pharmacology Faculty of Medicine University of Hong Kong 21 Sassoon Road Hong Kong China Department of Pharmacology Faculty of Medicine University of Hong Kong 21 Sassoon Road Hong Kong China Department of Pharmacology University of Hong Kong 21 Sassoon Road Hong Kong China

AIM: To detect the contents of four active components of Salvia miltiorrhiza in various commercially available danshen crude drugs and preparations. METHODS: Commercially available danshen crude drugs from different sources, as well as danshen pills and intravenous injection preparations containing danshen alone or in combination with other herbs were collected. The composition of these danshen samples was analyzed using HPLC. Specifically, the amounts of magnesium tanshinoate B (MTB), danshensu, isotanshinone IIA, and ctyptotanshinone were determined. In some of these samples, the content of MTB was further confirmed by liquid chromatography-tandem mass spectrometer (LC-MS)/MS method. RESULTS: There were great variations in the amount of the four active ingredients in the commercially available danshen crude drugs and drug preparations in this study. The amount of MTB was the highest among the four components measured in the crude drugs. However, the amounts of MTB in all danshen preparations were much

关键词： Salvia miltiorrhiza magnesium tanshinoate B (MTB) high pressure liquid chromatography

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Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

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World Journal of Gastroenterology 2024年第7期30卷 714-726页

作者： Pui-Yin leung Wenjing Chen Anissa N Sari Poojitha Sitaram Pui-Kei Wu susan Tsai Jong-In Park Department of Biochemistry Medical College of WisconsinMilwaukeeWI 53226United States Department of Surgery Medical College of WisconsinMilwaukeeWI 53226United States

BACKGROUND Pancreatic cancer is a leading cause of cancer-related *** activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug ***,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic *** previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell *** has not been tested for this *** To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell ***Δψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell *** viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive *** synergy between erlotinib and MitoQ was then analyzed using SynergyFinder *** preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line *** Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive *** triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of *** suggested that these drugs synergistically induced tumor cell *** with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each *** Our findings suggest tha

关键词： Pancreatic cancer Erlotinib Mitochondria-targeted ubiquinone Mitochondria Combination therapy

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Phytoestrogens and vascular responsiveness

Phytoestrogens and vascular responsiveness

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11th International Vascular Neuroeffector Mechanisms and Cardiovascular Pharmacology and Medicine Symposia, Shanghai-Suzhou 2006

作者： susan W.S.leung Mary Y.K.Lee Ricky Y.K.Man Department of Pharmacology Li Ka Shing Faculty of Medicine The University of Hong Kong China Department of Pharmacology Li Ka Shing Faculty of Medicine The University of Hong Kong China Department of Pharmacology Li Ka Shing Faculty of Medicine The University of Hong Kong China

Dietary intake of phytoestrogens has been associated with a reduction in risk of cardiovascular disorders including coronary heart disease, hypertension and atherosclerosis. Phytoestrogens have long been found to be structurally similar to the female sex hormone,17β-estradiol, and have a wide range of estrogenic effects. Like 17β-estradiol, phytoestrogens such as genistein have been suggested to exert its cardioprotective actions through favourable alteration of serum

关键词： Phytoestrogens and vascular responsiveness

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THE RELATIONSHIP BETWEEN HABITUAL CALCIUM INTAKE ＆ BONE MINERAL MASS OF CHILDREN:A LONGITUDINAL INVESTIGATION

THE RELATIONSHIP BETWEEN HABITUAL CALCIUM INTAKE ＆ BONE MIN...

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第一届国际骨质疏松和代谢性骨病研讨会

作者： WARREN T.K.LEE SOPHIE S.F.leung susan S.H.LUI JOSEPH LAU Department of Paediatrics The Chinese University of Hong Kong Centre for Clinical Trials and Epidemiological Research Faculty of MedicineThe Chinese University of Hong Kong

＜正＞This paper reports the association between habitual calcium intake from birth to 5 years in a longitudinal study of 128 healthy Hong Kong Chinese children（67 boys,61 girls） and their bone mineral content（BMC） achieved at S years of *** intakes was evaluated using diet history and cross-checked with food frequency and 24-h *** 5 years,BMC was determined at the distal 33%of the radial bone by single photon absorptiometry（Norland 2780）. At 5 years,the mean（SD） calcium intake was 546（325） mg/d,cow’s milk was the chief source of *** mean BMC was 0.317（0.042） g/*** was not significantly correlated with the current calcium ***,cumulative calcium intake from birth to 5 years showed a significant correlation with BMC attained at 5 years（r = 0.235,p = 0.0133）;this significant correlation remained even after adjusting for weight,height,bone width,sex,cumulative intakes of energy and protein by multiple regression analysis（r = 0.248,p = 0.0107）.Moreover,using principal component analysis,calcium intake at the second year of life had the strongest correlation with BMC attained at 5 years（r = 0.24,p = 0.02）.In conclusion,milk consumption is common amoung the younger generation of Hong *** calcium intake in preschool years was higher than the recommendation of FAO/WHO（1962） and amounted to 66%of the *** study demonstrates that habitual calcium intake throughout the preschool years,particularly at the second year of life,is important for bone ***,the importance of having higher BMC at 5 years in attaining peak bone mass or in protecting against future osteoporosis is not known and warrants further investigation.

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