College of Veterinary Medicine, Hunan Agricultural University, 1 Nongda Rd, District Furong, Changsha 410128, China.
Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, 1 Nongda Rd, District Furong, Changsha 410128, China.
Molecules. 2022 Apr 18;27(8):2605. doi: 10.3390/molecules27082605.
() is a toxic flowering plant in the family Loganiaceae used to treat skin diseases, neuralgia and acute pain. The high toxicity of restricts its development and clinical applications, but in veterinary applications, has been fed to pigs as a feed additive without poisoning. However, until now, the in vivo processes of the multiple components of have not been studied. This study investigates the excretion, metabolism and tissue distribution of the multiple components of after feeding it to pigs in medicated feed. Pigs were fed 2% powder in feed for 45 days. The plasma, urine, bile, feces and tissues (heart, liver, lung, spleen, brain, spinal cord, adrenal gland, testis, thigh muscle, abdominal muscle and back muscle) were collected 6 h after the last feeding and analyzed using high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Five natural products in plasma, twelve natural products and five metabolites in urine, and three natural products in feces were characterized, suggesting that multiple components from were excreted in the urine. However, ten natural products and four metabolites were detected in bile samples, which suggested that is involved in enterohepatic circulation in pigs. A total of seven of these metabolites were characterized, and four metabolites were glucuronidated metabolites. Ten natural products and six metabolites were detected in the tissues, which indicates that is widely distributed in tissues and can cross the blood-brain barrier. Among the characterized compounds, a highly toxic gelsedine-type alkaloid from was the main compound detected in all biological samples. This is the first study of the excretion, metabolism and tissue distribution of multiple components from in pigs. These data can provide an important reference to explain the efficacy and toxicity of . Additionally, the results of the tissue distribution of are of great value for further residue depletion studies and safety evaluations of products of animals fed .
() 是夹竹桃科的一种有毒开花植物，用于治疗皮肤病、神经痛和急性疼痛。 的高毒性限制了它的发展和临床应用，但在兽医应用中， 已作为饲料添加剂喂给猪而没有中毒。然而，到目前为止， 中多种成分的体内过程尚未被研究。本研究调查了在饲料中给猪喂食 后， 中多种成分的排泄、代谢和组织分布。猪用 2% 的 粉饲料喂养 45 天。最后一次喂养后 6 小时收集血浆、尿液、胆汁、粪便和组织（心、肝、肺、脾、脑、脊髓、肾上腺、睾丸、大腿肌肉、腹部肌肉和背部肌肉），并使用高效液相色谱-四极杆飞行时间质谱联用进行分析。在血浆中鉴定了 5 种天然产物，尿液中鉴定了 12 种天然产物和 5 种代谢产物，粪便中鉴定了 3 种天然产物，提示 中的多种成分从尿液中排泄。然而，在胆汁样本中检测到 10 种天然产物和 4 种代谢产物，这表明 在猪中涉及肠肝循环。共鉴定出 7 种代谢产物，其中 4 种为葡萄糖醛酸代谢产物。在组织中检测到 10 种天然产物和 6 种代谢产物，这表明 广泛分布于组织中，可以穿过血脑屏障。在所鉴定的化合物中， 是从 中提取的一种高毒性的冬凌草型生物碱，是所有生物样本中检测到的主要化合物。这是首次研究 在猪体内的排泄、代谢和组织分布。这些数据可为解释 的疗效和毒性提供重要参考。此外， 组织分布的结果对于进一步研究动物饲料产品的残留消除和安全性评估具有重要价值。
