A Kinetic Study of the Main Guaco Metabolites Using Syrup Formulation and the Identification of an Alternative Route of Coumarin Metabolism in Humans

Abstract

For decades guaco species have been empirically used for the treatment of respiratory diseases. However, studies have shown that the toxic and therapeutic effects of the main guaco metabolites are dose-dependent, and none clinical study was done to evaluate the behavior of these substances in humans. In this work, a pilot study measuring the kinetic profile of the main guaco metabolites was performed leading to the knowledge of an alternative route of coumarin metabolism in humans. Initial screenings demonstrated that the administration of 60 mL of guaco syrup (single dose) did not provide sufficient levels of coumarin (COU), 7-hydroxycoumarin (7-HCOU), o-coumaric acid (OCA) and kaurenoic acid (KAU). The pharmacokinetic parameters were calculated by orally administering 60 mL of guaco syrup spiked with 1500 mg of COU. The kinetic study demonstrated that the plasmatic levels of 7-HCOU (considered the main metabolite of COU) were 10 times lower than the levels of COU, and the kinetic profile of 7-HCOU suggests sequential metabolism in the liver with low access of 7-HCOU to the systemic circulation. The study also demonstrated that OCA is one of the main bioavailable metabolites of COU. Therefore, the hydrolysis of the lactone ring forming a carboxylated compound is one of the possible routes of COU metabolism in humans. The half-lives of COU, 7-HCOU and OCA were approximately 4.0, 1.0 and 3.0 h, respectively and there was evidence that the recommended dosage of guaco syrup did not provide sufficient levels of COU, 7-HCOU or OCA to obtain a bronchodilation effect. Clinical studies are necessary to prove the efficacy and safety of products based on guaco.

Nanopartículas de prata biossintetizadas por Mikania glomerata Sprengel inibem o crescimento de Candida albicans e Staphylococcus aureus

“…A espécie Mikania glomerata Sprengel., pertence à família Asteraceae e é popularmente conhecida no Brasil como guaco. É uma planta trepadeira e terrestre, amplamente utilizada na medicina popular devido a propriedades farmacológicas como antimicrobiano, antiinflamatório, vasodilatador, espasmódica, anti-estresse, entre outros 8,9 . Neste estudo foi considerado o extrato aquoso das folhas de M. glomerata, uma vez que estudos fitoquímicos já identificaram diversos compostos secundários presentes nas folhas, como esteroides, cumarinas, taninos, saponinas e alcalóides 10 .…”

New Metabolites of Coumarin Detected in Human Urine Using Ultra Performance Liquid Chromatography/Quadrupole-Time-of-Flight Tandem Mass Spectrometry

“…Neither free coumarin nor o -coumaric acid were detected in the volunteers’ urine. This result indicates that coumarin was completely metabolized before excretion and that o -coumaric acid found in human plasma [ 7 ] underwent a new biotransformation prior to excretion in the urine. Among all the metabolites detected in human urine, only o -hydroxyphenylacetic acid could be a candidate for metabolite of o -coumaric acid, considering their structural similarity.…”

“…Coumarin is also used for medicinal purposes. It is the main active component present in the medicinal plant guaco, which is widely used as tea and as syrup for the treatment of respiratory tract disorders [ 7 ]. Furthermore, coumarin is utilized in low doses (8.0 mg) for the treatment of venous constriction or in high doses (7.0 g) for anticancer therapy [ 8 ].…”

“…Recently, a pharmacokinetic study in humans reported that o -coumaric acid is an important metabolite of coumarin (approximately 30% of the plasma levels of coumarin) [ 7 ]. The identification of this new metabolite shows that contrary to what was previously known, coumarin metabolism has not been completely elucidated, possibly due to the limitations of old technologies.…”

ent-Kaurenoic acid-rich extract from Mikania glomerata: In vitro activity against bacteria responsible for dental caries

“…Many of these properties are due to the higher content of kaurane diterpenes in this plant, being KA one of the major constituents of M. glomerata preparations [17,18,19,20]. Therefore, we have decided to develop a KA-rich M. glomerata extract (KAMg) and evaluate it as a new proposal of herbal ingredient to be used in oral care products.…”