title: Comparative tissue distribution and excretion study of alkaloids from Herba Ephedrae-Radix Aconiti Lateralis extracts in rats.
abstract: Herba Ephedrae-Radix Aconiti Lateralis, composed of Ephedrae (Mahuang in Chinese) and Radix Aconiti Lateralis (Fuzi in Chinese), is a classical herbal combination proven to be effective in treating common cold, asthma, and rheumatoid arthritis. Alkaloids, bioactive components of the herbal extract, have been associated with many side effects. Nine alkaloids, including norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine, were simultaneously quantified within 14.5min, by a validated ultra-performance liquid chromatography-tandem mass spectrometry method in various rat tissues, urine, and feces after oral administration of Mahuang-Fuzi and single-herb extracts. The results indicated that the alkaloids were widely distributed in the heart, liver, spleen, lung, kidney, and brain. Lower bioavailability and higher clearance of some alkaloids were observed for the herbal combination, but hypaconitine showed a longer residence time and lower clearance. Elimination kinetics demonstrated that ephedra and aconitum alkaloids were mainly excreted in urine and feces, respectively. The tissue distribution and excretion of ephedra and aconitum alkaloids are comprehensively reported for the first time for the Mahuang-Fuzi combination. Compared with single-herb extracts, lower extraction efficiencies of alkaloids in vitro were observed which may result in their lower intake. However, the combination showed a prolonged residence time and delayed elimination of aconitum alkaloids, which increases the risk of drug accumulation. The study demonstrated potential risks of intoxication with aconitum alkaloids, associated with the use of Fuzi in combination with Mahuang. Mahuang-Fuzi is a classical combination used in clinics, further investigation is needed.
authors.affiliation: Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Mengyue
authors.initials: M
authors.lastname: Ren
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, China; School of Pharmacy, Anhui Medical University, Hefei 230000, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Song
authors.affiliation: Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Dedong
authors.initials: D
authors.lastname: Liang
authors.affiliation: Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Weiting
authors.initials: W
authors.lastname: Hou
authors.affiliation: Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. Electronic address: tanxm_smu@163.com.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Tan
authors.affiliation: Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. Electronic address: ljb@smu.edu.cn.
authors.forename: Jiabo
authors.initials: J
authors.lastname: Luo
mesh_terms: D031841:Aconitum; D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D004365:Drugs, Chinese Herbal / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000502:physiology
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal
keywords: Alkaloids; Distribution; Excretion; Mahuang-Fuzi; UPLC-MS-MS