title: Pharmacokinetics of hesperetin and naringenin in the Zhi Zhu Wan, a traditional Chinese medicinal formulae, and its pharmacodynamics study.
abstract: Zhi Zhu Wan (ZZW), a classical Chinese medical formulae consisted of Atractylodes Rhizome and Fructus Citrus Immaturus, has been commonly used for treatment of gastrointestinal diseases. Hesperetin and naringenin are the main components of ZZW, and both can alleviate intestinal tract disorders. In this work, plasma pharmacokinetics and pharmacodynamics characteristics of ZZW after oral administration were investigated using a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry method with an electrospray ionization source in positive ion mode. Biosamples were prepared using methanolic precipitation, and the separation of hesperetin and naringenin was achieved on a Waters ACQUITY HSS BEH (2.1 mm × 5 mm, 1.7 µm) column by linear gradient elution, and the total run time was only 3 min. Data were analyzed and estimated using WinNonlin Professional version 5.1. With pharmacokinetic analysis, the estimated pharmacokinetic parameters (i.e. C(max), area under the concentration-time curve (AUC) and t(1/2)), were C(max)  = 776.06 ng/mL, AUC = 9473 ng/mL·h, t1/2 = 5.26 h for hesperetin and C(max)  = 2910.6 ng/mL, AUC = 40607.9 ng/mL·h, t1/2 = 4.69 h for naringenin, respectively. In the present study, we have also valuated and clarified the effect of ZZW on small intestinal movement. It was found that ZZW can accelerate intestinal motility in mice and may hold a promising treatment for intestinal diseases.
authors.affiliation: National TCM Key Lab of Serum Pharmacochemistry, Heilongjiang University of Chinese Medicine, and Key Pharmacometabolomics Platform of Chinese Medicines, Heping Road 24, Harbin 150040, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Tianwei
authors.initials: T
authors.lastname: Dong
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Yang
authors.forename: Guangli
authors.initials: G
authors.lastname: Yan
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sakurai
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Xijun
authors.initials: X
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D031174:Atractylodes / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods; D002957:Citrus / Q000737:chemistry; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics* / Q000494:pharmacology; D044950:Flavanones / Q000493:pharmacokinetics* / Q000494:pharmacology; D005769:Gastrointestinal Motility; D006569:Hesperidin / Q000493:pharmacokinetics* / Q000494:pharmacology; D007422:Intestines / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010949:Plasma / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D004365:Drugs, Chinese Herbal; D044950:Flavanones; D006569:Hesperidin; C005273:naringenin; C013015:hesperetin