Planta Med
DOI: 10.1055/s-0043-113447
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Anti-Inflammatory Effects of Boldine and Reticuline Isolated from Litsea cubeba through JAK2/STAT3 and NF-κB Signaling Pathways

Xinyao Yang, *, Xiaoli Gao, *, Yuan Cao, Qiang Guo, Shanshan Li, Zhixiang Zhu, Yunfang Zhao, Pengfei Tu, Xingyun Chai
  • Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
Further Information

Publication History

received 07 December 2016
revised 10 May 2017

accepted 07 June 2017

Publication Date:
26 June 2017 (eFirst)

Abstract

The anti-inflammatory effects of boldine and reticuline isolated from Litsea cubeba were evaluated by using xylene-induced ear edema and carrageenan-induced paw edema in mice and rats. Our results demonstrated that intragastric administration with boldine and reticuline significantly mitigated ear weight in mice and decreased paw volume in rats. A combination administration of boldine (0.5 mg/kg) + reticuline (0.25 mg/kg) resulted in a potentiated inhibition in these two models. In parallel, boldine or reticuline reduce the infiltration of neutrophil leukocytes in rat paw tissue, respectively, and the combination of the two groups performed a better anti-inflammatory activity as shown in histopathologies. Boldine, reticuline, and their combination notably inhibited mRNA expressions of TNF-α, and IL-6 and reduced the phosphorylation levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Beyond that, their combination also can reduce the phosphorylation levels of p65 and IκBα in the pathological tissues of animals, as observed by real-time PCR and western blot analyses, respectively. These findings indicate for the first time that boldine and reticuline have not only anti-inflammatory activity but also potential synergistic effects in vivo. The underlying mechanism may relate to the inhibition on the expression of pro-inflammatory cytokines, such as TNF-α and IL-6, which may be a consequence of JAK2/STAT3 and NF-κB pathway involvements. This study provides useful data for further exploration and application of boldine and reticuline as potential anti-inflammatory medicines.

* The first two authors contributed to the paper equally.


Supporting Information