Characterization of phase I and phase II metabolites of hop (Humulus lupulus L.) bitter acids: In vitro and in vivo metabolic profiling by UHPLC-Q-Orbitrap.

Bitter acids are a class of prenylated phloroglucinol derivatives present in Humulus lupulus L., known for their multiple healthy properties, nevertheless, research regarding their metabolism and stability is lacking. This study was aimed to elucidate the metabolic stability of hop α- and ß-acids and characterize I and II phase metabolites in vitro and in vivo. For this purpose, an ultra high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) method was developed and validated. Mice liver microsomes were used to assess metabolic stability; in vitro t1/2 and clearance values were calculated, showing a moderate metabolism for α-acids (avgt1/2: 120.01 min, avgCLint 11.96 µL/min/mg), while ß-acids were metabolized faster (avgt1/2: 103.01 min, avgCLint: 13.83 µL/min/mg). I and II phase metabolites were characterized both in in vitro, and in vivo, in mouse plasma and urine after oral administration. A combined full scan/data dependent/precursor ion list-triggered neutral loss (FS/dd-MS2/PIL-tNL) strategy was used to detect unknown and expected metabolites. As a result, 33 compounds were detected, including novel metabolites, such as 9 potential oxidized metabolites of humulones (M6-M14), and 10 glucuronide conjugates of α-acids, comprising 7 glucuronide derivatives of oxidized phase I metabolites (M26-M32). The proposed method extends the current knowledge regarding metabolization of hop α- and ß-acids and could be applied for the comprehension of the metabolic fate of this class of compounds in different species, as well as for in vivo pharmacokinetic studies.

A Novel Promising Frontier for Human Health: The Beneficial Effects of Nutraceuticals in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) such as hypertension, atherosclerosis, myocardial infarction, and diabetes are a significant public health problem worldwide. Although several novel pharmacological treatments to reduce the progression of CVDs have been discovered during the last 20 years, the better way to contain the onset of CVDs remains prevention. In this regard, nutraceuticals seem to own a great potential in maintaining human health, exerting important protective cardiovascular effects. In the last years, there has been increased focus on identifying natural compounds with cardiovascular health-promoting effects and also to characterize the molecular mechanisms involved. Although many review articles have focused on the individual natural compound impact on cardiovascular diseases, the aim of this manuscript was to examine the role of the most studied nutraceuticals, such as resveratrol, cocoa, quercetin, curcumin, brassica, berberine and Spirulina platensis, on different CVDs.