# Physalin F, a Potent Inhibitor of Lymphocyte Function, Is a Calcineurin Inhibitor and Has Synergistic Effect with Dexamethasone

## TL;DR

Physalin F, a natural compound, suppresses immune responses and works better with dexamethasone, showing promise as a treatment for immune-related diseases.

## Contribution

Physalin F is identified as a calcineurin inhibitor with synergistic effects when combined with dexamethasone, offering a novel immunosuppressive strategy.

## Key findings

- Physalin F inhibits lymphocyte proliferation and reduces cytokine production in activated splenocytes.
- Combining physalin F with dexamethasone shows synergistic immunosuppressive effects in vitro.
- Physalin F reduces calcineurin activity and paw edema in a delayed-type hypersensitivity model in vivo.

## Abstract

The dysregulation of immune responses are responsible for the development of several diseases, such as allergic and autoimmune diseases. The medications used to treat these conditions have numerous side effects, creating the need for new drugs. Physalins are natural compounds with various pharmacological activities already described. Here, we aimed to investigate the immunomodulatory effects of physalin F in mouse splenocytes and in a delayed-type hypersensitivity (DTH) model. In a cytotoxicity assay, physalin F had low cytotoxicity to mouse splenocytes in concentrations equal to or below 2 µM. It significantly inhibited lymphocyte proliferation in a concentration-dependent manner and reduced the production of cytokines, including IL-2, IL-4, IL-10, and IFN-γ, in activated splenocytes. The combined therapy of physalin F with dexamethasone was investigated in vitro, showing a synergistic action of the two compounds. Mechanistically, physalin F reduced calcineurin activity in concanavalin A-stimulated splenocyte cultures. Finally, in vivo, the intraperitoneal administration of physalin F in a DTH model reduced paw edema induced by bovine serum albumin immunization. Our results demonstrate the potential of physalin F as an immunosuppressive agent, to be used alone or in combination with glucocorticoids.