TY - JOUR T1 - Berberine decreased iNOS mRNA stability through negative regulation of HuR in LPS-induced macrophages JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.115.231043 SP - jpet.115.231043 AU - Ji-Sun Shin AU - Hye-Eun Choi AU - SeungHwan Seo AU - Jung-Hye Choi AU - Nam-In Baek AU - Kyung-Tae Lee Y1 - 2016/01/01 UR - http://jpet.aspetjournals.org/content/early/2016/05/12/jpet.115.231043.abstract N2 - Berberine, a major isoquinoline alkaloid found in medicinal herbs, has been reported to possess anti-inflammatory effects. However, the underlying mechanisms responsible for its actions are poorly understood. In the present study, the authors investigated the inhibitory effects of berberine and the molecular mechanisms involved in LPS-treated RAW 264.7 and THP-1 macrophages and its effects in LPS-induced septic shock in mice. In both macrophage cell types, berberine inhibited the LPS-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) protein expression, but had no effect on iNOS mRNA transcription. Suppression of LPS-induced iNOS protein expression by berberine occurred via a human antigen R (HuR)-mediated reduction of iNOS mRNA stability. Molecular data revealed that the suppression on the LPS-induced HuR binding to iNOS mRNA by berberine was accompanied by a reduction in nucleocytoplasmic HuR shuttling. Pretreatment with berberine reduced LPS-induced iNOS protein expression, the cytoplasmic translocation of HuR in liver tissues and increased the survival rate of mice with LPS-induced endotoxemia. These results show that the suppression of iNOS protein expression by berberine under LPS-induced inflammatory conditions is associated with a reduction in iNOS mRNA stability due to inhibition of the cytoplasmic translocation of HuR. ER -