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Current Pharmaceutical Analysis


ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Tissue Distribution of Active Principles from Alpiniae Oxyphyllae Fructus Extract: An Experimental Study in Rats

Author(s): Qi Wen, Hai-Long Li, Shi-Ying Mai, Yin-Feng Tan* and Feng Chen*

Volume 15, Issue 3, 2019

Page: [286 - 293] Pages: 8

DOI: 10.2174/1573412914666180910102909


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 active principles.

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.

Keywords: Alpiniae Oxyphyllae Fructus (Yizhi) extract, tissue distribution, gastrointestinal tissues, flavonoids, diarylheptanoids.

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Zhang, Q.; Cui, C.; Chen, C.Q.; Hu, X.L.; Liu, Y.H.; Fan, Y.H.; Meng, W.H.; Zhao, Q.C. Anti-proliferative and pro-apoptotic activities of Alpinia oxyphylla on HepG2 cells through ROS-mediated signaling pathway. J. Ethnopharmacol., 2016, 169, 99-108.
Park, M.H.; Hong, J.E.; Park, E.S.; Yoon, H.S.; Seo, D.W.; Hyun, B.K.; Han, S.B.; Ham, Y.W.; Hwang, B.Y.; Hong, J.T. Anticancer effect of tectochrysin in colon cancer cell via suppression of NF-kappaB activity and enhancement of death receptor expression. Mol. Cancer, 2015, 14, 124.
Park, M.H.; Hong, J.E.; Hwang, C.J.; Choi, M.; Choi, J.S.; An, Y.J.; Son, D.J.; Hong, J.T. Synergistic inhibitory effect of cetuximab and tectochrysin on human colon cancer cell growth via inhibition of EGFR signal. Arch. Pharm. Res., 2016, 39, 721-729.
Shi, S.H.; Zhao, X.; Liu, A.J.; Liu, B.; Li, H.; Wu, B.; Bi, K.S.; Jia, Y. Protective effect of n-butanol extract from Alpinia oxyphylla on learning and memory impairments. Physiol. Behav., 2015, 139, 13-20.
Zhao, H.; Ji, Z.H.; Liu, C.; Yu, X.Y. Neuroprotective mechanisms of 9-hydroxy epinootkatol against glutamate-induced neuronal apoptosis in primary neuron culture. J. Mol. Neurosci., 2015, 56, 808-814.
Zhang, Z.; Li, G.; Szeto, S.S.; Chong, C.M.; Quan, Q.; Huang, C.; Cui, W.; Guo, B.; Wang, Y.; Han, Y.; Michael, S.K.W.; Yuen, L.S.M.; Chu, I.K. Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease. Free Radic. Biol. Med., 2015, 84, 331-343.
Ha, H.; Shim, K.S.; Kim, T.; Lee, C.J.; Park, J.H.; Kim, H.S.; Ma, J.Y. Water extract of the fruits of Alpinia oxyphylla inhibits osteoclast differentiation and bone loss. BMC Complement. Altern. Med., 2014, 14, 352.
Wang, C.Z.; Yuan, H.H.; Bao, X.L.; Lan, M.B. In vitro antioxidant and cytotoxic properties of ethanol extract of Alpinia oxyphylla fruits. Pharm. Biol., 2013, 51, 1419-1425.
Lin, R.J.; Yen, C.M.; Chou, T.H.; Chiang, F.Y.; Wang, G.H.; Tseng, Y.P.; Wang, L.; Huang, T.W.; Wang, H.C.; Chan, L.P.; Ding, H.Y.; Liang, C.H. Antioxidant, anti-adipocyte differentiation, antitumor activity and anthelmintic activities against Anisakis simplex and Hymenolepis nana of yakuchinone A from Alpinia oxyphylla. BMC. Comp. Altern. Med., 2013, 13, 237.
He, Z.H.; Ge, W.; Yue, G.G.; Lau, C.B.; He, M.F.; But, P.P. Anti-angiogenic effects of the fruit of Alpinia oxyphylla. J. Ethnopharmacol., 2010, 132, 443-449.
Zhang, J.; Wang, S.; Li, Y.; Xu, P.; Chen, F.; Tan, Y.; Duan, J. Anti-diarrheal constituents of Alpinia oxyphylla. Fitoterapia, 2013, 89, 149-156.
Wang, S.; Zhao, Y.; Zhang, J.; Huang, X.; Wang, Y.; Xu, X.; Zheng, B.; Zhou, X.; Tian, H.; Liu, L.; Mei, Q. Antidiarrheal effect of Alpinia oxyphylla Miq. (Zingiberaceae) in experimental mice and its possible mechanism of action. J. Ethnopharmacol., 2015, 168, 182-190.
Yuan, Y.; Tan, Y.F.; Xu, P.; Li, H.; Li, Y.H.; Chen, W.Y.; Zhang, J.Q.; Chen, F.; Huang, G.J. Izalpinin from fruits of Alpinia oxyphylla with antagonistic activity against the rat bladder contractility. Afr. J. Tradit. Complement. Altern. Med., 2014, 11, 120-125.
Li, Y.H.; Tan, Y.F.; Cai, H.D.; Zhang, J.Q. Metabonomic study of the fruits of Alpinia oxyphylla as an effective treatment for chronic renal injury in rats. J. Pharm. Biomed. Anal., 2016, 124, 236-245.
Chen, F.; Li, H.L.; Tan, Y.F.; Li, Y.H.; Lai, W.Y.; Guan, W.W.; Zhang, J.Q.; Zhao, Y.S.; Qin, Z.M. Identification of known chemicals and their metabolites from Alpinia oxyphylla fruit extract in rat plasma using liquid chromatography/tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring. J. Pharm. Biomed. Anal., 2014, 97, 166-177.
Wen, Q.; Li, H.L.; Tan, Y.F.; Zhang, X.G.; Qin, Z.M.; Li, W.; Li, Y.H.; Zhang, J.Q.; Chen, F. LC-MS/MS-based method for simultaneous quantification of known chemicals and metabolites of Alpiniae oxyphyllae Fructus extract in rat plasma and its application in a pharmacokinetic study. Anal. Meth, 2016, 8, 2069-2081.
Chen, F.; Li, H.L.; Li, Y.H.; Tan, Y.F.; Zhang, J.Q. Quantitative analysis of the major constituents in Chinese medicinal preparation SuoQuan formulae by ultra fast high performance liquid chromatography/quadrupole tandem mass spectrometry. Chem. Cent. J., 2013, 7, 131.
Scaldaferri, F.; Pizzoferrato, M.; Pecere, S.; Forte, F.; Gasbarrini, A. Bacterial flora as a cause or treatment of chronic diarrhea. Gastroenterol. Clin. North Am., 2012, 41(3), 581-602.
Lee, S.L.; Dou, J.H.; Agarwal, R.; Temple, R.; Beitz, J.; Wu, C.; Mulberg, A.; Yu, L.X.; Woodcock, J. Evolution of traditional medicines to botanical drugs. Science, 2015, 347, S32-S34.
Castro, J.G.; Chin-Beckford, N. Crofelemer for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on anti-retroviral therapy. Expert Rev. Clin. Pharmacol., 2015, 8, 683-690.
Biswal, S. Crofelemer: In HIV associated diarrhea and secretory diarrhea-a patent perspective. In: Recent. Pat. Antiinfect. Drug Discov; , 2014; 9, pp. 136-143.
Tobin, P.J.; Beale, P.; Noney, L.; Liddell, S.; Rivory, L.P.; Clarke, S. A pilot study on the safety of combining chrysin, a non-absorbable inducer of UGT1A1, and irinotecan (CPT-11) to treat metastatic colorectal cancer. Cancer Chemother. Pharmacol., 2006, 57, 309-316.
Baggio, C.H.; Freitas, C.S.; Mayer, B.; Dos, S.A.C.; Twardowschy, A.; Potrich, F.B.; Cipriani, T.R.; de Souza, L.M.; Sassaki, G.L.; Iacomini, M.; Marques, M.C.; Mesia-Vela, S. Muscarinic-dependent inhibition of gastric emptying and intestinal motility by fractions of Maytenus ilicifolia Mart ex. Reissek. J. Ethnopharmacol., 2009, 123, 385-391.
Andersson, K.E.; Wein, A.J. Pharmacology of the lower urinary tract: basis for current and future treatments of urinary incontinence. Pharmacol. Rev., 2004, 56, 581-631.
Gonzalez-Arancibia, C.; Escobar-Luna, J.; Barrera-Bugueno, C.; Diaz-Zepeda, C.; Gonzalez-Toro, M.P.; Olavarria-Ramirez, L.; Zanelli-Massai, F.; Gotteland, M.; Bravo, J.A.; Julio-Pieper, M. What goes around comes around: novel pharmacological targets in the gut-brain axis. Therap. Adv. Gastroenterol., 2016, 9, 339-353.
Visschers, R.G.; Luyer, M.D.; Schaap, F.G.; Olde, D.S.W.; Soeters, P.B. The gut-liver axis. Curr. Opin. Clin. Nutr. Metab. Care, 2013, 16, 576-581.
Chen, F.; Wen, Q.; Jiang, J.; Li, H.L.; Tan, Y.F.; Li, Y.H.; Zeng, N.K. Could the gut microbiota reconcile the oral bioavailability conundrum of traditional herbs? J. Ethnopharmacol., 2016, 179, 253-264.
Nallu, A.; Sharma, S.; Ramezani, A.; Muralidharan, J.; Raj, D. Gut microbiome in chronic kidney disease: challenges and opportunities. Transl. Res., 2017, 179, 24-37.

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