Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Am J Chin Med. 2022;50(6):1475-1527. doi: 10.1142/S0192415X2250063X. Epub 2022 Jul 23.
Nakai (AGN) root is a medicinal herbal widely used in traditional medicine in Korea. AGN root ethanolic extract dietary supplements are marketed in the United States for memory health and pain management. We comprehensively reviewed the anticancer, analgesic, pro-memory and other bio-activities of AGN extract and its signature phytochemicals decursin, decursinol angelate, and decursinol a decade ago in 2012 and updated their anticancer activities in 2015. In the last decade, significant progress has been made for understanding the pharmacokinetics (PK) and metabolism of these compounds in animal models and single dose human PK studies have been published by us and others. In addition to increased knowledge of the known bioactivities, new bioactivities with potential novel health benefits have been reported in animal models of cerebral ischemia/stroke, anxiety, sleep disorder, epilepsy, inflammatory bowel disease, sepsis, metabolic disorders, osteoporosis, osteoarthritis, and even male infertility. Herein, we will update PK and metabolism of pyranocoumarins, review bioactivities from animal models and human studies, and critically appraise the relevant active compounds, the cellular and molecular pharmacodynamic targets, and pertinent mechanisms of action. Knowledge gaps include whether human pyranocoumarin PK metrics are AGN dose dependent and subjected to metabolic ceiling, or metabolic adaptation after repeated use. Critical clinical translation challenges include sourcing of AGN extracts, product consistency and quality control, and AGN dose optimization for different health conditions and disease indications. Future research directions are articulated to fill knowledge gaps and address these challenges.
中田（AGN）根是一种在韩国传统医学中广泛使用的药用草药。AGN 根的乙醇提取物膳食补充剂在美国被销售用于记忆健康和疼痛管理。十年前，即 2012 年，我们全面综述了 AGN 提取物及其标志性植物化学物质紫花前胡苷、紫花前胡苷醇酯和紫花前胡甲素的抗癌、镇痛、促记忆等生物活性，并在 2015 年更新了它们的抗癌活性。在过去的十年中，人们在理解这些化合物在动物模型中的药代动力学（PK）和代谢方面取得了重大进展，我们和其他人已经发表了关于这些化合物的单剂量人体 PK 研究。除了对已知生物活性的认识不断增加外，在脑缺血/中风、焦虑、睡眠障碍、癫痫、炎症性肠病、败血症、代谢紊乱、骨质疏松症、骨关节炎，甚至男性不育症的动物模型中，也报道了具有潜在新型健康益处的新生物活性。在此，我们将更新吡喃香豆素的 PK 和代谢，综述来自动物模型和人体研究的生物活性，并批判性地评价相关的活性化合物、细胞和分子药效学靶点以及相关的作用机制。知识空白包括人体吡喃香豆素 PK 指标是否与 AGN 剂量有关，是否受代谢上限或重复使用后的代谢适应的影响。关键的临床转化挑战包括 AGN 提取物的来源、产品的一致性和质量控制，以及针对不同健康状况和疾病适应症的 AGN 剂量优化。未来的研究方向旨在填补知识空白并解决这些挑战。
