Sennoside A differentially regulates mast cell activation and attenuates gut allergic inflammation
Year: 2026
Type: preprint
Abstract: ABSTRACT Introduction Mast cells are central effectors of IgE-mediated allergic responses and reside in barrier tissues where they encounter diverse environmental compounds. How naturally occurring bioactive compounds influence mast cell function under resting versus allergic conditions remains poorly defined. Methods We compared the effects of cholera toxin, aconitine, and sennoside A on viability, degranulation, and cytokine production in murine bone marrow-derived mast cell. We then examined the acute physiological effects of oral sennoside A and its effects in an ovalbumin-induced mouse model of food allergy. Results None of the compounds reduced mast cell viability at the concentrations tested. Sennoside A, but not cholera toxin or aconitine, induced modest degranulation in resting mast cells without increasing TNF-α or IL-6 secretion. In contrast, sennoside A markedly suppressed IgE-dependent antigen-induced degranulation, TNF-α and IL-6 secretion, and Il1b expression. Acute oral sennoside A induced dose-dependent diarrhea and hypothermia and increased colonic Tnfa , Il1b , Il33 , and Hdc expression. In allergic mice, sennoside A attenuated allergen-induced hypothermia, reduced duodenal Tpsab1 expression, and decreased circulating total IgE, OVA-specific IgE, and OVA-specific IgG1, while increasing Il5 expression. Conclusion Sennoside A differentially regulates mast cell responses according to activation state and attenuates features of experimental food allergy. These findings identify a previously unrecognized immunomodulatory effect of sennoside A on IgE-driven mast cell activation. However, the mechanisms and the contribution of mast cells to the in vivo phenotype remain to be defined.
Institutions: Mayo Clinic, Mayo Clinic in Arizona, Arizona State University
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7214616562