1 | INTRODUCTION
The liver plays central roles in the maintenance of body homeostasis and is important to multiple metabolic functions and physiological processes such as bile production, energy generation, vitamin storage, and the metabolism of carbohydrates, proteins, and lipids [1]. Fatty liver disease is becoming progressively prevalent in numerous parts of the world, affecting about 25% of people globally [2]. High concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in hepatocytes are used as biochemical indicators of hepatocellular disease [3]. Results from several studies suggest that certain vitamins, herbs and dietary supplements may help lessen liver fat and reduce the risk of liver disease progression [4]. Furthermore, among supplements that may ameliorate fatty liver, silymarin; berberine has been great of interest [5-9]. BBR is an isoquinoline derivative alkaloid isolated from Rhizoma Coptidis (RC). The composition of BBR in RC is about 5.2% to 7.7%. BBR has been widely used as a drug in traditional Indian and Chinese medicinal plants [10, 11]. This plant is useful as cholesterol-lowering action and anti-hyperglycemic effect [12-16]. But BBR due to the presence of P-glycoprotein (P-gp) have low oral bioavailability. It has been recently formulated along with silymarin, and this component rich in flavolignanes (60–80%) and flavolignanes inhibits the transport of P-gp substrates, thus improving oral bioavailability of BBR [17]. Then, silymarin considered a fine candidate for combine with berberis aristate to improve the efficacy of liver function [18].
BBR by anti-dyslipidemic [19, 20], anti-hyperglycemic [20] and anti-inflammatory effect [21-25] may play a role in improving the nonalcoholic fatty liver disease (NAFLD). Silymarin has anti-inflammatory effect such as reduction of Tumor Necrosis Factor Alpha (TNF-α) [26, 27], and alleviate oxidative stress by (Superoxide Dismutase (SOD), Glutathione (GSH), Glutathione Peroxidase (GPx) activity) [28], antifibrotic activity [26]. Also BBR inhibited the 5-lipoxygenase pathway [29]. In the past study we observed improve in lipid and glucose profile with silymarin; berberine [30]. Also, BBR [31, 32] and silymarin [33-36] lonely effect on the liver function and improve in liver enzymes.
The aim of our meta‐analysis was to systematically summarize the effects of the BBR–silymarin supplementation on liver enzymes using randomized controlled trials (RCTs).