Wang Dongpeng, Wang Xian-He, Yu Xiongjie, Cao Fengjun, Cai Xiaojun, Chen Ping, Li Minglun, Feng Yibin, Li Hongliang, Wang Xuanbin
Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China.
Biomedical Research Institute, Hubei Key Laboratory of Wudang Local Chinese Medicine Research and School of Pharmacy, Hubei University of Medicine, Shiyan, China.
Front Pharmacol. 2021 Apr 15;12:638993. doi: 10.3389/fphar.2021.638993. eCollection 2021.
Anthraquinones are bioactive natural products, some of which are active components in medicinal medicines, especially Chinese medicines. These compounds exert actions including purgation, anti-inflammation, immunoregulation, antihyperlipidemia, and anticancer effects. This study aimed to review the pharmacokinetics (PKs) of anthraquinones, which are importantly associated with their pharmacological and toxicological effects. Anthraquinones are absorbed mainly in intestines. The absorption rates of free anthraquinones are faster than those of their conjugated glycosides because of the higher liposolubility. A fluctuation in blood concentration and two absorption peaks of anthraquinones may result from the hepato-intestinal circulation, reabsorption, and transformation. Anthraquinones are widely distributed throughout the body, mainly in blood-flow rich organs and tissues, such as blood, intestines, stomach, liver, lung, kidney, and fat. The metabolic pathways of anthraquinones are hydrolysis, glycuronidation, sulfation, methylation/demethylation, hydroxylation/dehydroxylation, oxidation/reduction (hydrogenation), acetylation and esterification by intestinal flora and liver metabolic enzymes, among which hydrolysis, glycuronidation and sulfation are dominant. Of note, anthraquinones can be transformed into each other. The main excretion routes for anthraquinones are the kidney, recta, and gallbladder. Conclusion: Some anthraquinones and their glycosides, such as aloe-emodin, chrysophanol, emodin, physcion, rhein and sennosides, have attracted the most PK research interest due to their more biological activities and/or detectability. Anthraquinones are mainly absorbed in the intestines and are mostly distributed in blood flow-rich tissues and organs. Transformation into another anthraquinone may increase the blood concentration of the latter, leading to an increased pharmacological and/or toxicological effect. Drug-drug interactions influencing PK may provide insights into drug compatibility theory to enhance or reduce pharmacological/toxicological effects in Chinese medicine formulae and deserve deep investigation.
蒽醌类是具有生物活性的天然产物，其中一些是药物尤其是中药中的活性成分。这些化合物具有泻下、抗炎、免疫调节、降血脂和抗癌等作用。本研究旨在综述蒽醌类的药代动力学（PKs），其与药理和毒理作用密切相关。蒽醌类主要在肠道吸收。由于游离蒽醌的脂溶性较高，其吸收速率比其结合糖苷快。肝肠循环、重吸收和转化可能导致蒽醌类血药浓度波动及两个吸收峰。蒽醌类广泛分布于全身，主要在血流丰富的器官和组织，如血液、肠道、胃、肝脏、肺、肾脏和脂肪中。蒽醌类的代谢途径包括肠道菌群和肝脏代谢酶的水解、葡萄糖醛酸化、硫酸化、甲基化/去甲基化、羟基化/脱羟基化、氧化/还原（氢化）、乙酰化和酯化，其中水解、葡萄糖醛酸化和硫酸化占主导。值得注意的是，蒽醌类可相互转化。蒽醌类的主要排泄途径是肾脏、直肠和胆囊。结论：一些蒽醌类及其糖苷，如芦荟大黄素、大黄酚、大黄素、大黄素甲醚、大黄酸和番泻苷，因其具有更多生物活性和/或可检测性而吸引了最多的PK研究关注。蒽醌类主要在肠道吸收，大多分布于血流丰富的组织和器官。转化为另一种蒽醌可能会增加后者的血药浓度，导致药理和/或毒理作用增强。影响PK的药物相互作用可为中药方剂中增强或降低药理/毒理作用的药物配伍理论提供见解，值得深入研究。
