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  • br Financial support This work was supported by


    Financial support This work was supported by Fondation pour la Recherche Médicale (Equipe labellisée, DEQ20150331724), Inserm, University of Lille, and Agence Nationale pour la Recherche (ANR-10-LBEX-46 and ANR-10-INBS-08; ProFI project, “Infrastructures Nationales en Biologie et Santé”; “Investissements d'Avenir” call); FP7-Health Resolve 305707. CM received a PhD fellowship from the French Ministry of Research. BS is a recipient of an Advanced ERC Grant (694717).
    Conflict of interest Please refer to the accompanying ICMJE disclosure forms for further details.
    Authors’ contribution
    Introduction Bile acids (BAs) homeostasis have crucial role in lipid, glucose and energy metabolism (Houten et al., 2006, Kuipers et al., 2014, Verkade et al., 1995). Enzymatic oxidation of cholesterol generates various distinct bile acids in the liver, secreted with phospholipids, cholesterol, drugs, and toxic metabolites into gallbladder to maintain the size and composition of the BA pool (Chiang, 2013, Marin et al., 2015). Primary BAs, under the deconjugation and dehydroxylation of gut microbial enzymes, are metabolized to unconjugated BAs and secondary BAs. BAs act as hormones to activate four distinct receptors including, farnesoid X receptor (FXR), pregnane X receptor (PXR), vitamin D receptor (VDR) and one G-protein-coupled receptor (TGR5) (de Aguiar Vallim et al., 2013). FXR in the ileum and liver are considered as the most essential transcriptional regulator to modulate BA synthesis, influx, efflux, and detoxification along the enterohepatic axis (Mazuy et al., 2015). Bile MK-4827 hydrochloride disorders are associated with metabolic diseases such as hepatobiliary diseases (Crosignani et al., 1991, Stanimirov et al., 2015), gallstones (Berr et al., 1992), and gastrointestinal cancers (Bernstein et al., 2005). Recent studies demonstrated that BAs act as biomarkers in liver diseases (Masubuchi et al., 2016). BAs were more sensitive than some traditional assays for liver disease than clinical chemistry, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) (Anwer and Meyer, 1995, Kurumiya et al., 2003). Polygonum multiflorum Thunb, also known as Heshouwu (HSW) in China, has been used as an anti-aging agent in oriental countries for centuries. processed HSW is often used for nourishing liver and kidney, supplementing essence and blood, strengthening bones and muscles (Lei et al., 2015). HSW is always used in different herbal formulas, or can be used as a single herb (Lin et al., 2015). Pharmaceutically active chemical compounds isolated from HSW have been shown to possess various bioactivities, including, anti-tumor (Chen et al., 2011), anti-inflammatory (Lin et al., 2017), anti-oxidant (Lv et al., 2014), and anti-diabetic (Yang et al., 2017). However, previous studies and clinical data showed that overconsumption of HSW agents can lead to liver damage with clinical symptoms such as jaundice, fatigue, anorexia, and yellow or tawny urine (Lei et al., 2015). The occurrence of hepatotoxicity cases linked to HSW has raised serious concerns regarding HSW safety.
    Materials and methods
    Discussion The occurrence of hepatotoxicity cases linked to HSW has raised serious concerns regarding HSW safety. HSW may cause liver toxicity and liver damage without age or gender orientation (Lei et al., 2015, Teschke et al., 2014). It is demonstrated that processed HSW exhibited lower toxicity than raw HSW. Acetone extract of processed HSW (100 g/kg/day of the crude material) displayed no toxicity or death during the 14 consecutive days of administration (Wu et al., 2012). However, in clinical cases, the duration of use varied greatly. Toxic hepatitis would have developed in patients who had ingested it only for 1 or 2 days (Jung et al., 2011). Our results indicated that high dose of HSW, 3.825 g/kg in a mouse equals 108 g HSW intake per day for a 60-kg human individual, 9 times of the upper dosage for human recommended in Chinese Pharmacopoeia (0.2 g/kg), did not cause liver damage within one week. It has been shown previously that bile secretion pathway was associated with HSW induced liver injury, which suggested that HSW may cause bile acid disruptions (Y.Y. Wang et al., 2017). The present data suggest that HSW treatment within a short time could not cause a liver damage. However, the concentration of BAs was decreased in both liver and serum in mice treated with HSW.