Background: Alpiniae Oxyphyllae Fructus (Yizhi in Chinese) have been widely used as an
herbal medicine for the treatment of diuresis, enuresis and diarrhea in China. Many studies have deciphered
some potential underlying mechanisms for its anti-diarrheal effects. However, tissue distribution
of Yizhi constituents is warranted because pharmacological receptors are frequently located in tissues.
Moreover, it is also interesting to know about the potential correlation between behavior in drug distribution
and the observed pharmacological response. The aim of this study is to investigate tissue distribution
behaviors of Yizhi constituents after oral administration of Yizhi extract to rats, focusing on 10
Methods: Twenty four male Sprague Dawley rats were given orally the Yizhi extract and fourteen tissue
samples were collected after being killed by bleeding from the abdominal aorta under ether anesthesia
at different time-points. The resulting tissues were excised and homogenized. Based on our previous
reports, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to quantify
the target analytes, as well as phase II metabolites, in the various biosamples.
Results: Almost all the targeted Yizhi active principles and some glucuronidated metabolites were
qualitatively measured in rat stomach, small intestine, large intestine, as well as liver. Nootkatone,
yakuchinone A and tectochrysin were observed in the rat brain. In other rat tissues, these analytes had
lower exposure or could not be detected. Consistently, quantitative analysis revealed that the Yizhi active
principles dominantly distributed into gastrointestinal tissues followed by liver, the overall exposure
levels ranking as follows: stomach > small intestine > large intestine > liver. Tissue concentrationtime
profiles of the test active principles in rat stomach, small intestine, and large intestine were bimodal
with two concentration peaks occurring at 0.5 and 4h after oral administration, respectively. The
exposure levels in rat kidney and bladder were quite low.
Conclusion: The active principles of Yizhi were specially distributed into gastrointestinal tissues after
oral administration of its ethanol extract to rats. The tissue distribution behaviors partly supported its
anti-diarrheal effects from a pharmacokinetic opinion. This paper will be useful as the starting point for
studying the pharmacological activities of this traditional herb.