Blaškovič Dušan, Zižková Petronela, Držík Filip, Viskupičová Jana, Veverka Miroslav, Horáková Lubica
Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dúbravská cesta 9, 841 01 Bratislava, Slovak Republic.
Interdiscip Toxicol. 2013 Mar;6(1):3-8. doi: 10.2478/intox-2013-0001.
Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) is the pump crucial for calcium homeostasis and its impairment results in pathologies such as myopathy, heart failure or diabetes. Modulation of SERCA activity may represent an approach to the therapy of diseases with SERCA impairment involvment. Quercetin is flavonoid known to modulate SERCA activity. We examined the effect of nine novel quercetin derivatives on the activity of the pump. We found that 5-morpholinohydroxypoxyquercetin, di(prenylferuoyl)quercetin, di(diacetylcaffeoyl)-mono-(monoacetylcaffeoyl)quercetin and monoacetylferuloylquercetin stimulated the activity of SERCA. On the contrary, monochloropivaloylquercetin, tri(chloropivaloyl)quercetin, pentaacetylquercetin, tri(trimethylgalloyl)quercetin and diquercetin inhibited the activity of the pump. To identify compounds with a potential to protect SERCA against free radicals, we assessed the free radical scavenging activity of quercetin derivatives. We also related lipophilicity, an index of the ability to incorporate into the membrane of sarcoplasmic reticulum, to the modulatury effect of quercetin derivatives on SERCA activity. In addition to its ability to stimulate SERCA, di(prenylferuloyl)quercetin showed excellent radical scavenging activity.
肌浆网Ca(2+)-ATP酶（SERCA）是维持钙稳态的关键泵，其功能受损会导致如肌病、心力衰竭或糖尿病等病理状况。调节SERCA活性可能是治疗涉及SERCA功能受损疾病的一种方法。槲皮素是一种已知可调节SERCA活性的黄酮类化合物。我们研究了九种新型槲皮素衍生物对该泵活性的影响。我们发现5-吗啉羟基氧基槲皮素、二（异戊二烯阿魏酰基）槲皮素、二（二乙酰咖啡酰基）-单-（单乙酰咖啡酰基）槲皮素和单乙酰阿魏酰基槲皮素刺激了SERCA的活性。相反，一氯新戊酰基槲皮素、三（氯新戊酰基）槲皮素、五乙酰基槲皮素、三（三甲基没食子酰基）槲皮素和双槲皮素抑制了该泵的活性。为了鉴定具有保护SERCA免受自由基损伤潜力的化合物，我们评估了槲皮素衍生物的自由基清除活性。我们还将脂溶性（一种衡量融入肌浆网膜能力的指标）与槲皮素衍生物对SERCA活性的调节作用联系起来。除了刺激SERCA的能力外，二（异戊二烯阿魏酰基）槲皮素还表现出优异的自由基清除活性。
