Anti-colitic Effects of Physalin B on Dextran Sodium Sulfate-Induced BALB/c Mice by Suppressing Multiple Inflammatory Signaling Pathways

Ethnopharmacological relevance: Physalin B is one of the main active withanolide existed in Physalis alkekengi L. var. franchetii (Mast.) Makino, a famous traditional Chinese food and herbal medicine, which has been widely used as heat-clearing and toxin-resolving medicine for the treatment of various inflammatory disease, such as cough, excessive phlegm, pharyngitis, sore throat, pemphigus, eczema, and jaundice.

Aim of the study: We aimed to confirm the therapeutic effects of Physalin B on ulcerative colitis (UC) and enrich the further application of its traditional anti-inflammatory effect.

Materials and methods: The anti-UC effects of Physalin B were evaluated in Balb/c mice with dextran sulfate sodium (DSS) induction. The body weight, colon length, disease activity index (DAI) and pathological changes of colon tissue were measured. Cytokine levels were detected by ELISA. NF-κB pathway and protein levels of related pathways, such as signal transducer and activator of transcription 3 (STAT3), β-arrestin1 and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome were detected by western blot.

Results: The dose of Physalin B that is not cytotoxic could dramatically reduce the levels of TNF-α, IL-6 and IL-1β on LPS-stimulated RAW 264.7 cells. Meanwhile, Physalin B dramatically improved clinical signs and symptoms, alleviated body weight loss and colon length shortening in DSS-induced UC mice. Meanwhile, Physalin B also dramatically relieved the pathological damage, reduced in the activity of myeloperoxidase (MPO) and reestablished the balance of pro-inflammatory cytokines. Physalin B could suppress DSS-induced activation of NF-κB. Moreover, Physalin B also markedly suppressed the activation of STAT3, β-arrestin1 and NLRP3 inflammasome.

Conclusion: This study preliminary confirmed the therapeutic effect of Physalin B on experimental acute UC mice and provided robust evidence support for the anti-inflammatory effect of Physalin B, suggesting that Physalin B might be a potential agent for the therapeutic efficacy on UC.

Keywords: DSS; NF-κB; NLRP3; Physalin B; The list of chemical compounds using PubChem CID'S immediately: Physalin B (PubChem CID:431000); Ulcerative colitis; β-arrestin1.