Herbal hepatoprotective drugs modulate Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-like spheroids and psoriasis-like keratinocytes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common comorbidity of psoriasis, a chronic non-communicable inflammatory skin disease. This research project aimed at investigating the effect of herbal hepatoprotective drugs and silymarin on chronic inflammation in cellular models of MASLD and psoriasis. Three-dimensional (3D) liver spheroids were obtained from HepG2/LX-2 cells, and 3D multicellular liver spheroids were generated from human primary hepatocytes, Kupffer cells and liver endothelial cells. The spheroids were transformed to steatotic and inflamed MASLD-like spheroids by treating them with free fatty acids, fructose and LPS. Then the MASLD-like spheroids were treated with the herbal drugs Hepar SL™ and Iberogast™, the flavonolignan silymarin, the monoclonal anti-IL-17A antibody ixekizumab, and the acetyl-CoA carboxylase inhibitor firsocostat. Subsequently, the degree of steatosis and release of pro-inflammatory cytokines was assessed. In vitro generated psoriasis-like keratinocytes were treated with the same compounds or were exposed to conditioned media (CM) from MASLD-like spheroids. The herbal compounds demonstrated various anti-inflammatory effects in both MASLD-like spheroids and psoriasis-like keratinocytes. Silymarin also displayed an anti-steatotic effect in MASLD-like spheroids. In psoriasis-like keratinocytes, some herbal compounds reduced the psoriatic phenotype and inflammation markers, as did CM from MASLD-like spheroids treated with herbal compounds. This indicates that hepatoprotective herbal drugs, particularly silymarin, can modulate steatosis and inflammatory markers in in‑vitro models of MASLD and psoriasis. The clinical relevance of these findings remains to be established in dedicated pharmacokinetic and clinical studies.