Dietary bioflavonoids inhibit Escherichia coli ATP synthase in a differential manner

Abstract

The aim of this study was to determine if the dietary benefits of bioflavonoids are linked to the inhibition of ATP synthase. We studied the inhibitory effect of seventeen bioflavonoid compounds on purified F1 or membrane bound F1FO E. coli ATP synthase. We found that the extent of inhibition by bioflavonoid compounds was variable. Morin, silymarin, baicalein, silibinin, rimantadin, amantidin, or, epicatechin resulted in complete inhibition. The most potent inhibitors on molar scale were morin (IC50 ~0.07mM) > silymarin (IC50 ~0.11mM) > baicalein (IC50~0.29mM) > silibinin (IC50 ~0.34mM) > rimantadine (IC50 ~2.0mM) > amantidin (IC50 ~2.5mM) > epicatechin (IC50 ~4.0mM). Inhibition by hesperidin, chrysin, kaempferol, diosmin, apigenin, genistein, or rutin was partial in the range of 40–60% and inhibition by galangin, daidzein, or luteolin was insignificant. The main skeleton, size, shape, geometry, and position of functional groups on inhibitors played important role in the effective inhibition of ATP synthase. In all cases inhibition was found fully reversible and identical in both F1Fo membrane preparations isolated purified F1. ATPase and growth assays suggested that the bioflavonoids compounds used in this study inhibited F1-ATPase as well as ATP synthesis nearly equally, which signifies a link between the beneficial effects of dietary bioflavonoids and their inhibitory action on ATP synthase.

Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A

“…Chrysin resulted in lower (16%) while fisetin caused higher (46%) decrease of ATP than the above listed flavonoid aglycones. These results are in accordance with the previous investigations discussed in the introductory section [5][6][7][8][9]. Interestingly, after 24-h treatment a significant elevation (about 20%) of ATP levels was caused by luteolin.…”

“…1) to explore their influence on intracellular ATP levels in MDCK kidney-derived cell line using primarily the luciferin-luciferase ATP dependent bioluminescent reaction. In agreement with the previous studies most of the applied flavonoids caused no or only a mild decrease of intracellular ATP concentrations [5][6][7][8][9]. In contrast, the flavone DIOS exerted a significant increase in ATP levels therefore, our experiments were focused on the investigation of this aglycone.…”

“…Previous studies highlighted that besides their scavenger property flavonoids exerted influence on the activity of several enzymes, transporters and on cell signaling pathways [1]. Interestingly, based on our current knowledge all of the previous investigations suggested that at least some of the studied flavonoids were able to decrease intracellular ATP levels [5][6][7][8][9]. Chinnam et al described the inhibition of Escherichia coli (E. coli) ATP synthase on purified F 1 subunit or membrane bound F 1 Fo complexes related to different dietary bioflavonoids [5].…”

“…Interestingly, based on our current knowledge all of the previous investigations suggested that at least some of the studied flavonoids were able to decrease intracellular ATP levels [5][6][7][8][9]. Chinnam et al described the inhibition of Escherichia coli (E. coli) ATP synthase on purified F 1 subunit or membrane bound F 1 Fo complexes related to different dietary bioflavonoids [5]. Li et al observed similar inhibitory effect of theaflavins on E. coli ATP synthase [6]: They suggested the F 1 part as the primary site of inhibition and they also reported the inhibition of electron transport chain.…”

Antimycobacterial Activity Some Different Lamiaceae Plant Extracts Containing Flavonoids and Other Phenolic Compounds

“…Until 2004, it was suggested Lamb, 2005, 2011) that their antibacterial efficacy was dependent upon cytoplasmic membrane damage by perforation (Ikigai et al, 1993), inhibition of nucleic acid synthesis (Mori et al, 1987) and disruption of energy metabolism due to NADH-cytochrome c reductase inhibition (Haraguchi et al, 1998). Currently, some other supporting mechanisms have emerged to indicate the role of flavonoids in antibacterial activity; these mechanisms include damage to the cytoplasmic membrane by generating hydrogen peroxide (Tamba et al, 2007;Kusuda et al, 2006;Sirk et al, 2008), inhibition of nucleic acid synthesis (Gradisar et al, 2007;Wang et al, 2010) and inhibition of ATP synthase (Chinnam et al, 2010). While Puupponen-Pimiä et al (2001) reported that catechin, rutin and quercetin did not affect the growth of E. coli, Vaquero et al, (2007) reported that quercetin was the strongest inhibitor active against bacteria, dependent on concentration.…”