Content area
Full Text
Introduction
Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder, which occurs predominantly during the third trimester of pregnancy (1). ICP is characterized by pruritus, jaundice, high serum bile acid levels and abnormal liver function, which adversely affects fetal health (1). Although the etiology of ICP is not fully understood, previous results have suggested that female hormones may have a causative role (2).
Previous findings have indicated an etiologic role for estrogens in the initiation of ICP (3). ICP typically occurs in the last trimester, when estrogen levels are highest (4). In addition, ICP is more common in multiple pregnancies compared with single pregnancies (5). The estrogen oral contraceptive used among women with a personal or family history of ICP may result in clinical features of ICP, including pruritus, elevated serum aminotransferases and bile acid levels, particularly when former high-dose preparations were used (6).
The synthetic estrogen 17α-ethinylestradiol (EE) has been demonstrated to reduce bile flow formation in experimental animals (7). In vitro studies have reported that EE impairs the expression and function of hepatocyte transporters, including multidrug resistance-associated protein 2 (MRP2) and the bile salt export pump (BSEP), which have important roles in bile salt-dependent component of bile flow (BSDF) and bile salt-independent flow (BSIF) (8–10). Furthermore, ICP induced by EE in rodents is an established animal model to assess the mechanisms of estrogen-induced cholestasis (11).
Herb decoction of Chinese medicine is an effective method and has been used in the clinic to treat ICP (12,13). Yin Huang Mixture (YHHJ; patent no. 200910031240.7) is a clinical experiential decoction that was formulated in the Maternal and Child Health Medical Institute (Obstetrics and Gynecology Hospital, Nanjing, China) and was predominantly composed of Artemisia capillaries Thunb, Hypericum japonicum Thunb, Eucommia ulmoides Oliver, Rheum officinale Baill, Gardenia jasminoides Ellis, Poria cocos Wolf and Dictamnus dasycarpus Turcz. YHHJ has been used to treat ICP in clinic for decades. YHHJ has previously been revealed to ameliorate itching and reduce serum bile acid levels, is well tolerated by pregnant women and has no adverse effects in mothers or newborns (14,15). However, the molecular mechanism of YHHJ on ICP remains to be elucidated.
The present study focused on the action of YHHJ in regulating membrane transporters, particularly MRP2, which transports lipophilic substances...