Insulin plant (Costus igneus) extract alleviates steatosis and adiposity in a murine MASLD model by modulating hepatic lipogenesis and the CD9-CFD immunoregulatory axis.

Metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent liver condition associated with obesity and type 2 diabetes mellitus, can progress to severe metabolic dysfunction-associated steatohepatitis (MASH). Notwithstanding recent advances in pharmacotherapy of MASH with fibrosis, treatments for early-stage disease remain limited. This study investigates the therapeutic potential of an ethanolic extract of Costus igneus, the "insulin plant powder" (IPP), in MASLD. Phytochemically, the IPP extract was rich in flavonoids (rutin, naringin, and apigenin) known for antioxidative and anti-inflammatory properties. In cultured HepG2 cells, IPP significantly attenuates lipid accumulation induced by oleic acid and modulates intracellular calcium dysregulation caused by palmitic acid. In a 12-week study on C57BL/6 J mice fed a high-fat/high-fructose/high-cholesterol diet (HF-HFC), IPP mitigated body mass gain, adiposity, fasting glucose levels, and steatosis. Furthermore, IPP reduced liver triglycerides and serum alanine aminotransferase, indicating improved liver function. IPP downregulated lipid metabolism and inflammation markers, including Srebp-1c and Tgf-β. Focused Nanostring analysis revealed complement factor D as the principal upregulated gene in mice on HF-HFC (25x vs. control). IPP treatment reduced its level to half while also increasing Cd9 transcripts. Hepatic CFD and CD9 protein levels were significantly increased after IPP treatment. These findings show the potential of IPP as a supplemental therapeutic option modulating the immune-metabolic axis and underscoring the value of polypharmacology in the management of MASLD. The beneficial effects of IPP are likely due to the synergistic anti-inflammatory actions of its bioactive compounds and warrant further investigation in a clinical setting.