acacetin and tilianin

Agastache mexicana has been used in traditional medicine for relief of abdominal pain and treatment of other diseases. Two subspecies have been identified: A. mexicana ssp. mexicana (AMM) and A. mexicana ssp. xolocotziana (AMX) and both are used traditionally without distinction or in combination.. To determine the effect of methanol extracts of A. mexicana ssp. mexicana and A. mexicana ssp. xolocotziana on gut motility and their possible mechanism of action.. The effect of AMM and AMX methanol extracts were tested on the spontaneous activity in the isolated guinea pig ileum and on tissues pre-contracted with KCl, electrical field stimulation (EFS) or ACh. In addition, the possible mechanism of action of each subspecies on gut motility was analyzed in the presence of hexametonium, indomethacin, L-NAME, verapamil, atropine or pyrylamine. A comparative chromatographic profile of these extracts was also done to indicate the most abundant flavonoids presents in methanol extracts of both subspecies.. AMM, but not AMX, induced a contractile effect in the guinea pig ileum. This spasmogenic effect was partially inhibited by atropine, antagonist of muscarinic receptors; and pyrilamine, antagonist of H. These results suggest that in folk medicine only AMX should be used as spasmolytic, and not in combination with AMM as traditionally occurs, due to the spasmogenic effects of the latter. In addition, activation of nicotinic receptors, prostaglandins and calcium channels, but not nitric oxide mechanisms, could be responsible for the spasmolytic activity of AMX. On the other hand, release of ACh and histamine could be involved in the spasmogenic effect induced by AMM. Acacetin and tilanin are present in methanol extracts of both subspecies and both flavonoids were more abundant in AMX than AMM. Our findings contribute to the validation of the traditional use of Agastache mexicana in relieving gastrointestinal disorders, but indicate that the subspecie that should be used for this effect is A. mexicana ssp. xolocotziana.

Topics: Agastache; Animals; Flavones; Flavonoids; Flowers; Glycosides; Guinea Pigs; Ileum; In Vitro Techniques; Male; Methanol; Muscle Contraction; Muscle, Smooth; Parasympatholytics; Plant Extracts; Solvents

Triple recycling (i.e., enterohepatic, enteric and local recycling) plays a central role in governing the disposition of phenolics such as flavonoids, resulting in low systemic bioavailability but higher gut bioavailability and longer than expected apparent half-life. The present study aims to investigate the coexistence of these recycling schemes using model bioactive flavonoid tilianin and a four-site perfused rat intestinal model in the presence or absence of a lactase phlorizin hydrolase (LPH) inhibitor gluconolactone and/or a glucuronidase inhibitor saccharolactone. The result showed that tilianin could be metabolized into tilianin glucuronide, acacetin, and acacetin glucuronide, which are excreted into the bile and luminal perfusate (highest in the duodenum and lowest in the colon). Gluconolactone (20 mM) significantly reduced the absorption of tilianin and the enteric and biliary excretion of acacetin glucuronide. Saccharolactone (0.1 mM) alone or in combination of gluconolactone also remarkably reduced the biliary and intestinal excretion of acacetin glucuronide. Acacetin glucuronides from bile or perfusate were rapidly hydrolyzed by bacterial β-glucuronidases to acacetin, enabling enterohepatic and enteric recycling. Moreover, saccharolactone-sensitive tilianin disposition and glucuronide deconjugation, which was more active in the small intestine than the colon, points to the small intestinal origin of the deconjugation enzyme and supports the presence of local recycling scheme. In conclusion, our studies have demonstrated triple recycling of a bioactive phenolic (i.e., a model flavonoid), and this recycling may have an impact on the site and duration of polyphenols pharmacokinetics in vivo.

Topics: Administration, Oral; Animals; Bile; Biological Availability; Flavones; Flavonoids; Glucaric Acid; Gluconates; Glucuronidase; Glucuronides; Glycosides; Half-Life; Intestinal Mucosa; Lactase-Phlorizin Hydrolase; Lactones; Male; Rats; Rats, Sprague-Dawley

Flavonoids occur naturally as glucosides and aglycones. Their common phenolic hydroxyl groups may trigger extensive UDP-glucuronosyltransferase (UGT)- catalysed metabolism. Unlike aglycones, glucosides contain glucose moieties. However, the influence of these glucose moieties on glucuronidation of glucosides and aglycones remains unclear. In this study, the flavonoid glucoside tilianin and its aglycone acacetin were used as model compounds. The glucuronidation characteristics and enzyme kinetics of tilianin and acacetin were compared using human UGT isoforms, liver microsomes and intestinal microsomes obtained from different animal species. Tilianin and acacetin were metabolized into different glucuronides, with UGT1A8 produced as the main isoform. Assessment of enzyme kinetics in UGT1A8, human liver microsomes and human intestinal microsomes revealed that compared with tilianin, acacetin displayed lower Km (0.6-, 0.7- and 0.6-fold, respectively), higher Vmax (20-, 60- and 230-fold, respectively) and higher clearance (30-, 80- and 300-fold, respectively). Furthermore, glucuronidation of acacetin and tilianin showed significant species- and gender-dependent differences. In conclusion, glucuronidation of flavonoid aglycones is faster than that of glucosides in the intestine and the liver. Understanding the metabolism and species- and gender-dependent differences between glucosides and aglycones is crucial for the development of drugs from flavonoids.

Topics: Animals; Female; Flavones; Flavonoids; Glucosides; Glucuronosyltransferase; Glycosides; Glycosylation; Humans; Intestinal Mucosa; Isoenzymes; Kinetics; Male; Microsomes; Microsomes, Liver; Models, Molecular; Organ Specificity; Recombinant Proteins; Sex Factors; Species Specificity

To study the chemical constituents from the whole plant of Dracocephalum moldavica.. The compounds were isolated using RA polystyrene resin and silica gel column chromatography, and the structures were elucidated by means of spectral method.. Four compounds were identified as tilianin, agastachoside, acacetin and oleanolic acid.. All the compounds were isolated from this plant for the first time.

Topics: Flavones; Flavonoids; Glycosides; Lamiaceae; Oleanolic Acid; Plants, Medicinal