Yinzhihuang Oral Liquid Ameliorates Hyperbilirubinemia Induced by δ-Aminolevulinic Acid and Novobiocin in Neonatal Rats.

Yinzhihuang oral liquid (YZH) is a traditional Chinese medicine that has been widely used in Asia to prevent and treat neonatal hyperbilirubinemia, but the published preclinical studies on its anti-hyperbilirubinemia effect are conducted in adult animals, partly due to the lack of preclinical neonatal hyperbilirubinemia animal models. In the present study, we tested six reagents to induce hyperbilirubinemia in neonatal rats, and established two appropriate neonatal hyperbilirubinemia rat models by subcutaneous injection of δ-Aminolevulinic acid (ALA, 200 mg/kg) or novobiocin (NOVO, 200 mg/kg). Oral treatment of YZH (80, 160 and 320 mg/kg) significantly decreased serum conjugated bilirubin levels in ALA-treated neonatal rats and serum unconjugated bilirubin levels in NOVO-treated neonatal rats, respectively. Additionally, pre-treatment of YZH also prevented the increase of serum bilirubin levels in both ALA- and NOVO-treated rats. Mechanistically, YZH significantly up-regulated the mRNA expression of genes involved in hepatic bilirubin disposition (organic anion-transporting polypeptide 1b2, Oatp1b2; multidrug resistance-associated protein 2, Mrp2) and bilirubin conjugation (UDP-glucuronosyltransferase 1a1, Ugt1a1). Additionally, YZH up-regulated the mRNA expression of cytochrome P450 1A1 (Cyp1a1), the target gene of aryl hydrocarbon receptor (AhR), and increased the nuclear protein levels of AhR in livers of neonatal rats. YZH and its two active ingredients, namely baicalin (BCL) and 4'-hydroxyacetophenone (4-HT), up-regulated the mRNA expression of AhR target genes (CYP1A1 and UGT1A1) and increased nuclear protein levels of AhR in HepG2 cells. In conclusion, the present study provides two neonatal hyperbilirubinemia animal models and evaluates the anti-hyperbilirubinemia effect and mechanisms of YZH in neonatal animals.

The Anti-Depression-Like Effects of Zhengtian Capsule via Induction of Neurogenesis and the Neurotrophic Signaling Pathway.

Oxidative stress that causes neural damages in neurodegenerative disorders has been widely studied for the pathogenesis and diagnostic measures. Zhengtian capsule (ZTC), a type of traditional Chinese medicine for headaches, has been found to have extra effects in recent years, such as promoting the release of serotonin and dopamine in the brain, but its specific mechanism has not been clearly elucidated. In this study, we focus on revealing whether ZTC can regulate key proteins of neurotrophic signaling pathway to alleviate depression-like behavior caused by oxidative stress. Experimental results show that ZTC (M 0.34 and H 0.7 g/kg) can elevate the proliferation of neural stem cells and GABAergic-type neurons in the hippocampus, promote the protein levels of BDNF, phosphorylated ERK1/2, and CREB, and inhibit the expression level of a key inflammation factor NFκB in a dose-dependent manner. These data suggest ZTC acts on multiple pathways to resist excessive oxidative stress, proving it to be a potential neurotrophic drug.