Biophytis SA, Sorbonne Université, 4 Place Jussieu, F-75005 Paris, France.
Biophytis SA, Sorbonne Université, 4 Place Jussieu, F-75005 Paris, France; Metabrain Research, 19 Ave du Professeur Cadiot, 94700 Maisons-Alfort, France.
J Steroid Biochem Mol Biol. 2021 Sep;212:105897. doi: 10.1016/j.jsbmb.2021.105897. Epub 2021 Apr 20.
Ecdysteroids are not endogenous to mammals, but are normal components of the food intake of many mammalian species consuming phytoecdysteroid-containing plants. The most frequently encountered phytoecdysteroid is 20-hydroxyecdysone (20E). Several pharmaceutical effects have been observed after ecdysteroid injection or ingestion, but it is not clear to what extent metabolites generated in the mammalian body contribute to these effects. The C21-ecdysteroid poststerone (Post) is a metabolite of 20E in rodents. Post analogues are key intermediates in the metabolism of exogenous ecdysteroids possessing a C20/22-diol. The pharmacokinetics, bioavailability and metabolism of Post have been assessed in male rats after ingestion and injection. The bioavailability of Post is significantly greater than that of 20E and the presence of an efficient entero-hepatic cycle allows Post to be effectively metabolised to a wide range of metabolites which are excreted mainly in the faeces, but also to some extent in the urine. Several of the major metabolites in the bile have been identified unambiguously as 3-epi-poststerone, 16α-hydroxypoststerone, 21-hydroxypoststerone and 3-epi-21-hydroxypoststerone. Conjugates are also present. Parallels are drawn to the metabolism of endogenous vertebrate steroid hormones, to which Post bears more similarity than 20E.
蜕皮甾酮不是哺乳动物的内源性物质，但却是许多以含有植物蜕皮甾酮的植物为食的哺乳动物的正常食物成分。最常见的植物蜕皮甾酮是 20-羟基蜕皮甾酮（20E）。在注射或摄入蜕皮甾酮后，观察到了几种药物作用，但尚不清楚哺乳动物体内生成的代谢物在多大程度上促成了这些作用。C21-蜕皮甾酮后甾酮（Post）是啮齿动物中 20E 的代谢物。Post 类似物是具有 C20/22-二醇的外源性蜕皮甾酮代谢的关键中间体。在雄性大鼠中评估了摄入和注射后 Post 的药代动力学、生物利用度和代谢。Post 的生物利用度明显大于 20E，并且存在有效的肠肝循环，使得 Post 能够有效地代谢为广泛的代谢物，这些代谢物主要在粪便中排泄，但在一定程度上也在尿液中排泄。已明确鉴定出胆汁中几种主要代谢物为 3-差向-poststerone、16α-羟基-poststerone、21-羟基-poststerone 和 3-差向-21-羟基-poststerone。还存在共轭物。与内源性脊椎动物甾体激素的代谢进行了对比，Post 与 20E 相比更相似。
