title: Pharmacokinetic difference of berberine between normal and chronic visceral hypersensitivity irritable bowel syndrome rats and its mechanism.
abstract: Berberine is one of active alkaloids from Rhizoma coptidis in traditional Chinese medicine. The pharmacokinetics of berberine in rat plasma were compared between normal and chronic visceral hypersensitivity irritable bowel syndrome rats (CVH-IBS) established by mechanical colon irritation using angioplasty balloons for 2 weeks after oral administration of berberine hydrochloride (25 mg/kg) with the equivalent dose of 22 mg/kg for berberine according to body weight. Immunohistochemical analysis of c-fos and myosin light chain kinase (MLCK) and immunofluorescence analysis of MLCK in rat colon were conducted. Quantification of berberine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. The great different pharmacokinetic behavior of berberine was observed between normal and CVH-IBS model rats. Compared with normal group, T1/2 and AUC(0-t) of berberine in the model group were significantly increased, respectively (573.21 ± 127.53 vs 948.22 ± 388.57 min; 8,657.19 ± 1,562.54 vs 11,415.12 ± 1,670.72 min.ng/ml). Cl/F of berberine in the model group significantly decreased, respectively (13.89 ± 1.69 vs 9.19 ± 2.91 L/h/kg). Additionally, the expressions of c-fos and MLCK in model group were higher than those in normal group. The pharmacokinetic behavior of berberine was significantly altered in CVH-IBS pathological conditions, which indicated the dosage modification of berberine hydrochloride in CVH-IBS were necessary. Especially, improved exposure to berberine in rat plasma in CVH-IBS model rats was attributed to increased the expression of MLCK.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No.16, Dongzhimen Nei Nanxiao Road, Dongcheng District, Beijing, 100700, People's Republic of China.|Provincial Key Laboratory of Pharmaceutics in Guizhou Province, School of Pharmacy, Guiyang Medical University, No.9, Beijing Road, Yunyan District, Guiyang, 550004, People's Republic of China.
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No.16, Dongzhimen Nei Nanxiao Road, Dongcheng District, Beijing, 100700, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No.16, Dongzhimen Nei Nanxiao Road, Dongcheng District, Beijing, 100700, People's Republic of China.
authors.forename: Ruijie
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No.16, Dongzhimen Nei Nanxiao Road, Dongcheng District, Beijing, 100700, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No.16, Dongzhimen Nei Nanxiao Road, Dongcheng District, Beijing, 100700, People's Republic of China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No.16, Dongzhimen Nei Nanxiao Road, Dongcheng District, Beijing, 100700, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No.16, Dongzhimen Nei Nanxiao Road, Dongcheng District, Beijing, 100700, People's Republic of China.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No.16, Dongzhimen Nei Nanxiao Road, Dongcheng District, Beijing, 100700, People's Republic of China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Weng
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No.16, Dongzhimen Nei Nanxiao Road, Dongcheng District, Beijing, 100700, People's Republic of China.
authors.forename: Xuchen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No.16, Dongzhimen Nei Nanxiao Road, Dongcheng District, Beijing, 100700, People's Republic of China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No.16, Dongzhimen Nei Nanxiao Road, Dongcheng District, Beijing, 100700, People's Republic of China. zhuxiaoxin@icmm.ac.cn.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Guang'an Men Hospital, China Academy of Chinese Medical Sciences, No.5, Beixiange Road, Xicheng District, Beijing, 100053, People's Republic of China. dongyu250541@sina.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001599:Berberine / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006207:Half-Life; D043183:Irritable Bowel Syndrome / Q000503:physiopathology*; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D001599:Berberine; D009219:Myosin-Light-Chain Kinase
keywords: Berberine; Chronic visceral hypersensitivity irritable bowel syndrome; Myosin light chain kinase; Pharmacokinetic; Systemic exposure