Background. Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that commonly affects the health of many individuals. Esculentoside A (EsA), a saponin extracted from the roots of Phytolacca esculenta, has antioxidative and anti-inflammatory effects against various diseases. Nonetheless, its role in UC is undetermined. Hence, in this study, we examined the therapeutic effects of EsA in UC. Methods. Primary intestinal neuronal cells (in vitro) were treated with lipopolysaccharide (LPS) to induce inflammatory injury. An in vivo UC rat model was created by the administration of dextran sulfate sodium (DSS) to rats, which were subsequently treated with different doses of EsA. The effects of EsA on intestinal motility, histological score, inflammatory response, hydrogen sulfide (H2S)/cystathionine γ-lyase (CSE) system, NO/neuronal nitric oxide synthase (nNOS) system, and LPS-induced primary intestinal neuronal cell viability loss, proliferation inhibition, and apoptosis were detected. Results. In vitro, EsA treatment increased the number of DSS-inhibited bowel movements and body weight, improved the histological score of colitis, and inhibited the inflammatory response by reducing IL-6 and TNF-α levels in rats. More importantly, EsA reduced the NO and H2S levels in serum and CSE, CBS, and nNOS expressions in the colon tissue. In vivo, EsA treatment eased the viability loss, proliferation inhibition, and apoptosis of LPS-stimulated primary intestinal neuronal cells, as well as inhibited the expressions of IL-6, TNF-α, CSE, CBS, and nNOS in cells. Conclusion. EsA improved intestinal motility and suppressed inflammatory response in DSS-induced UC, which may be mediated by H2S/CSE and NO/nNOS systems.

Background: Esculentoside A (EsA) has had a remarkable curative effect on a variety of experimental acute and chronic inflammatory and autoimmune diseases. However, the role of EsA in the pathological process of ulcerative colitis (UC) is still unknown.Methods: Rat colonic smooth muscle cells (SMCs) were identified by immunofluorescence. The effect of EsA and/or lipopolysaccharide (LPS) on the viability, proliferation, and apoptosis of SMCs was explored via 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, and TdT-mediated dUTP nick end labeling (TUNEL) staining, respectively.The changes of apoptosis-related proteins were performed via western blotting. The expression and nuclear translocation of NF-κB were detected via western blotting, immunohistochemistry (IHC), and immunofluorescence staining, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of IL-6 and TNF-α. Results:The EsA treatment greatly up-regulated the viability of LPS-suppressed SMCs. The LPSinduced cell apoptosis was significantly reversed by EsA treatment, which was achieved via down-regulating Bax and cleaved caspase-3 expression and up-regulating Bcl-2 expression. In addition, LPS-induced IL-6, TNF-α expression and NF-κB activation were also largely decreased when treated with EsA. In vivo, the TNBS-induced colon injury including crypt destruction and crypt deformation, disorder, epithelial cell remains or complete destruction, and inflammatory cell infiltration was recovered by EsA treatment. The secretion of IL-6 and TNF-α in the serum of the model group was also down-regulated by EsA treatment.The expression of Bax, cleaved caspase-3, and Bcl-2 showed similar trends as those observed in the in vitro experiments.Conclusions: Our data provides supportive evidence that EsA can relieve the symptoms of UC and be used as a drug candidate for the treatment of UC.