Modulation of rabbit muscle sarcoplasmic reticulum Ca2+-ATPase activity by novel quercetin derivatives

Abstract

Sarcoplasmic reticulum Ca2+-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.

Distinct Action of Flavonoids, Myricetin and Quercetin, on Epithelial Cl−Secretion: Useful Tools as Regulators of Cl−Secretion

“…Alternatively, the action of quercetin on the forskolin-stimulated Isc might be by downregulating the Na + , K + -ATPase. Indeed, Mezesova et al [ 40 ] have reported that treatment with quercetin (20 mg · kg −1 · day −1 ) in both normotensive and hypertensive rats produces impairment in the affinity of Na + binding site of the Na + , K + -ATPase like the inhibitory action on Ca 2+ -ATPase [ 41 , 42 ]. On the other hand, myricetin showed no inhibitory action but stimulatory action on Isc, suggesting that myricetin would not inhibit NKCC or produce impairment in the affinity of Na + binding site of the Na + , K + -ATPase unlike quercetin.…”

Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells

“…Moreover, methods for the preparation of quercetin metabolites have also been developed [5], [6]. The quercetin derivatives synthesized to date include, for instance, esters of quercetin and of various aliphatic [7], [8] and aromatic carboxylic acids [9], [10], [11], quercetin-amino acid conjugates with amino acids attached to quercetin via a carbamate linkage [12], esters of sulfuric acid (i.e. quercetin sulfates) [13], [14], glycosides [15], glucuronides [5], methyl ethers [16], etc.…”

Dissection of the Effects of Quercetin on Mouse Myocardium

“…One of the most common flavonoids in human diet is quercetin (3,3′,4′,5,7‐pentahydroxyflavone), which occurs in nature in several different chemical forms . It has multiple biological effects such as excellent radical scavenging activity , anti‐inflammatory and relaxation of vascular smooth muscle . Quercetin pre‐treatment protected against myocardium ischaemia–reperfusion injury by decreasing oxidative stress, repressing inflammatory cascades and inhibiting apoptosis in vivo .…”