Involved in the inactivation of the cardiac medication and plant natural product digoxin, thus decreasing drug efficacy and toxicity. Catalyzes the reduction of the alpha,beta-unsaturated butyrolactone ring of digoxin to the inactive metabolite dihydrodigoxin. Likely uses the cytochrome Cgr1 as the physiological electron donor, encoded by the adjacent gene in the locus. Only reduces digoxin and other cardenolide toxins, such as digitoxin, digoxigenin, ouabain and ouabagenin. Therefore is a specialized enzyme present in some gut bacteria E.lenta that protects their human host against ingested plant toxins. digoxin + 2 Fe(II)-[cytochrome c] + 3 H(+) = dihydrodigoxin + 2 Fe(III)-[cytochrome c] digitoxin + 2 Fe(II)-[cytochrome c] + 3 H(+) = dihydrodigitoxin + 2 Fe(III)-[cytochrome c] digoxigenin + 2 Fe(II)-[cytochrome c] + 3 H(+) = dihydrodigoxigenin + 2 Fe(III)-[cytochrome c] 2 Fe(II)-[cytochrome c] + 3 H(+) + ouabain = dihydroouabain + 2 Fe(III)-[cytochrome c] 2 Fe(II)-[cytochrome c] + 3 H(+) + ouabagenin = dihydroouabagenin + 2 Fe(III)-[cytochrome c] kcat is 0.23 sec(-1) for the reduction of digoxin. May form a membrane-associated complex with Cgr1. Is highly up-regulated by digoxin and other cardiac glycosides containing unsaturated butyrolactone rings, such as digitoxin, digoxigenin, and, to a lesser extent, ouabain. Is repressed by arginine but not by ornithine. Part of an operon that consists of cgr1 and cgr2. Predicted to be exported by the Tat system. The position of the signal peptide cleavage has not been experimentally proven. Digoxin is a toxic chemical produced by plants that, in low doses, can be used to treat heart failure and arrhythmia. cgr operon presence and abundance predicted the extent of drug inactivation by human gut microbial communities in ex vivo incubations, and is restricted to E.lenta species. Data about the gut microbes in nearly 1,900 people from three continents revealed that bacteria that can produce Cgr2 were present in the guts of more than 40% of the individuals, although often in low abundance. Belongs to the FAD-dependent oxidoreductase 2 family.