Gynostemma pentaphyllum saponins attenuate inflammation in vitro and in vivo by inhibition of NF-κB and STAT3 signaling

// Wing-Yan Wong 1, * , Magnolia Muk-Lan Lee 1, * , Brandon Dow Chan 1, * , Victor Wan-San Ma 3 , Wenchun Zhang 2 , Timothy Tak-Chun Yip 3 , Wing-Tak Wong 1 and William Chi-Shing Tai 1, 2 1 Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong S.A.R., China 2 State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute of The Hong Kong Polytechnic University, Shenzhen, China 3 Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong S.A.R., China * These authors contributed equally to this work Correspondence to: William Chi-Shing Tai, email: william-cs.tai@polyu.edu.hk Keywords: gynostemma pentaphyllum saponins, inflammatory bowel disease, macrophages, colitis, anti-inflammation Received: May 24, 2017 Accepted: August 29, 2017 Published: September 18, 2017 ABSTRACT Recent advances in the development of anti-inflammatory agents have improved their therapeutic outcome in inflammatory bowel disease (IBD), however, the presence of side effects and limited effectiveness hinder their widespread use. Therefore, novel compounds with strong anti-inflammatory efficacy are still required. In this study, we investigated the anti-inflammatory effect and potential mechanisms of Gynostemma pentaphyllum (Thunb.) Makino saponins (GpS), a major component of the herbal medicine widely used in Asian countries. In in vitro studies, we demonstrated that GpS dose dependently suppressed activation of macrophages, one of the main effectors in IBD. GpS also suppressed cytokine production and the activation of NF-κB and STAT3 signaling in lipopolysaccharide-induced macrophages, without affecting their viability. Further in vivo studies demonstrated that GpS could ameliorate the weight loss, increased disease activity index, colon shortening and histological damage associated with dextran sulfate sodium (DSS)-induced colitis in mice. In agreement with results from our in vitro experiments, GpS suppressed cytokine production and activation of NF-κB and STAT3 signaling in the colons of DSS-induced mice. In this study, we present for the first time, evidence of the therapeutic effect of GpS in IBD, highlighting its potential as an effective therapeutic against the disease.