RESUMEN
Recent findings from the World Heart Federation (WHF) reported a significant increase in cardiovascular disease (CVD)-related deaths, highlighting the urgent need for effective prevention strategies. Atherosclerosis, a key precursor to CVD, involves the accumulation of low-density lipoprotein (LDL) and its oxidation within the endothelium, leading to inflammation and foam cell formation. Ginger extracts, known for their antioxidative and anti-inflammatory properties, show promise in preventing CVD initiation by inhibiting LDL oxidation and reducing foam cell formation. Our results revealed that the active fractions in ginger extracts had antioxidative effects, particularly fractions D and E. Further research is needed to identify the active compounds in these fractions and understand their mechanisms of action. In this context, microfluidic models could offer insights into the effects of ginger on monocyte recruitment in a more physiologically relevant context. Overall, ginger extracts represent a potential novel treatment for preventing CVD initiation, but additional studies are necessary to identify the active molecules in these fractions.
Asunto(s)
Células Espumosas , Extractos Vegetales , Zingiber officinale , Zingiber officinale/química , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/tratamiento farmacológico , Lipoproteínas LDL/metabolismo , Antioxidantes/farmacología , Aterosclerosis/metabolismo , Aterosclerosis/prevención & control , Aterosclerosis/tratamiento farmacológico , Moléculas de Adhesión Celular/metabolismoRESUMEN
Tetrahydroisoquinoline (THIQ) alkaloids and their derivatives have a structural similarity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a well-known neurotoxin. THIQs seem to present a broad range of actions in the brain, critically dependent on their catechol moieties and metabolism. These properties make it reasonable to assume that an acute or chronic exposure to some THIQs might lead to neurodegenerative diseases including essential tremor (ET). We developed a method to search for precursor carbonyl compounds produced during the Maillard reaction in overcooked meats to study their reactivity with endogenous amines and identify the reaction products. Then, we predicted in silico their pharmacokinetic and toxicological properties toward the central nervous system. Finally, their possible neurological effects on a novel in vitro 3D neurosphere model were assessed. The obtained data indicate that meat is an alkaloid precursor, and we identified the alkaloid 1-benzyl-1,2,3,4-tetrahydroisoquinoline-6,7-diol (1-benz-6,7-diol THIQ) as the condensation product of phenylacetaldehyde with dopamine; in silico study of 1-benz-6,7-diol-THIQ reveals modulation of dopamine receptor D1 and D2; and in vitro study of 1-benz-6,7-diol-THIQ for cytotoxicity and oxidative stress induction does not show any difference after 24 h contact for all tested concentrations. To conclude, our in vitro data do not support an eventual neurotoxic effect for 1-benz-6,7-diol-THIQ.
Asunto(s)
Alcaloides , Tetrahidroisoquinolinas , Tetrahidroisoquinolinas/toxicidad , Dopamina/metabolismo , Alcaloides/toxicidad , Encéfalo/metabolismoRESUMEN
Essential tremor (ET) is one of the most prevalent neurological disorders in the world. Environmental factors have been implicated in the pathogenesis of ET. In particular, epidemiological studies have suggested that neurotoxic agents, especially ß-carboline alkaloids (ßCAs), might be generated through Maillard-type reaction. ßCAs are molecules which are members of a large group of heterocyclic amines (HCAs, the so-called products of cooking meat). ßCAs are highly tremorogenic in animals, producing a marked generalized action tremor soon after systemic administration in a wide range of laboratory animals such as mice, rats and monkeys. Administration of ßCAs remains currently the main experimental model of ET. We review the pathogenesis of ET, with a focus on the biochemistry of ßCAs, their occurrence and biological activity, their endogenous biosynthesis, their formation in food, their toxicokinetics and their neurotoxicity. We highlight open questions regarding the effects of ßCAs in humans.