A pilot study on clinical pharmacokinetics and preclinical pharmacodynamics of (+)-epicatechin on cardiometabolic endpoints. Issue 1 (24th November 2017)

• Record Type: Journal Article
• Authors: Moreno-Ulloa, Aldo; Nájera-García, Nayelli; Hernández, Marcela; Ramírez-Sánchez, Israel; Taub, Pam R.; Su, Yongxuan; Beltrán-Partida, Ernesto; Ceballos, Guillermo; Dugar, Sundeep; Schreiner, George; Best, Brookie M.; Ciaraldi, Theodore P.; Henry, Robert R.; Villarreal, Francisco
• Is Part Of: Food & function. Volume 9:Issue 1(2018)
• Page Start: 307
• Page End: 319
• Publication Date: 2017-11-24
• Subjects: Food -- Analysis -- Periodicals; Food -- Composition -- Periodicals; Nutrition -- Periodicals; 664.07
• DOI: 10.1039/c7fo01028a
• Languages: English
• ISSNs: 2042-6496

Abstract

Abstract : We reported that (−)-epicatechin can stimulate mitochondria biogenesis and improve metabolism. Abstract : We reported that (−)-epicatechin can stimulate mitochondria biogenesis and improve metabolism. However, preliminary studies indicate that the (+) stereoisomer form may be more potent. We evaluated in a preliminary manner, the pharmacokinetics (PK) and initial safety analysis of (+)-epicatechin ((+)-Epi) in healthy and pre-diabetic subjects. Using a mouse model of diet-induced obesity and insulin resistance, we also evaluated the metabolic effects of (+)-Epi vs. (+)-catechin (Cat) to determine class effects. In the Phase I PK study, subjects were provided a single incremental oral dose of (+)-Epi (10, 30 or 100 mg). For the PD study, subjects were provided a single 30 mg dose per day for 7 days. Blood samples were collected and safety measures were performed. Incremental doses of (+)-Epi increase the half-life of blood metabolites from 1.2–4.9 h. The compound was well tolerated and no adverse effects were reported. Seven day dosing of pre-diabetic subjects led to tendencies for reductions in circulating levels of tumor necrosis factor-α and monocyte chemoattractant protein-1, which returned to baseline by 7 days after treatment. In animals, 2 weeks of oral dosing (0.003, 0.01, 0.03, 0.1 and 0.3 mg kg −1 day −1 ) dose dependently improved metabolism-related endpoints (weight gain, glucose, cholesterol, triglyceride, with thresholds as low as 0.01 mg kg −1 day −1 ). Cat yielded no effects at 0.1 mg kg −1 day −1 . Results indicate that (+)-Epi evidences a favorable PK and safety profile. Using a pre-clinical model, the compound positively modulates metabolism, which may link to mitochondrial effects. Effects are not due to general antioxidant actions, as Cat yielded no effects.