Targeting GLP-1 signaling and barrier integrity with Leanskolin™, a standardized Coleus forskohlii extract: a Caco-2 cell-based study for metabolic health support

Abstract

Glucagon-like peptide-1 (GLP-1) is a key incretin hormone involved in glucose regulation and metabolic health. This study reports, for the first time, the GLP-1 enhancing potential of a standardized Coleus forskohlii extract (Leanskolin™, ≥ 10% forskolin) using differentiated Caco-2 cells. MTT assay was performed to assess the cytotoxicity of Leanskolin (25–500 µg/mL) in Caco-2 cells. Later, the cells were treated with non-cytotoxic concentrations (25, 50, and 100 µg/mL) for 24 h. Further, in vitro Dipeptidyl peptidase-4 (DPP-4) enzyme inhibition assay was performed. At 100 µg/mL, Leanskolin significantly upregulated Proglucagon (3.33-fold, p  < 0.001) and GLP-1R (3.32-fold, p  < 0.01) gene expression, indicating stimulation of endogenous GLP-1 signaling. The extract also markedly inhibited cellular DPP-4 activity and its gene expression ( p  < 0.05 vs. control). In vitro DPP-4 inhibition assay revealed an IC₅₀ of 262.5 µg/mL of Leanskolin, suggesting potential to prolong GLP-1 bioavailability. Furthermore, Leanskolin modulated bitter taste receptor genes ( TAS2R38 , TAS2R43 , TAS2R14 ) in a concentration-dependent manner ( p  < 0.05), implicating a role in nutrient sensing and enteroendocrine signaling. Leanskolin treatment (25–100 µg/mL, 24 h) did not alter TEER values but significantly reduced FITC-flux at 50 and 100 µg/mL ( p  < 0.01), indicating improved barrier integrity. Importantly, the extract enhanced the expression of tight junction (TJ) proteins ( p  < 0.05 vs. control). These findings highlight the multi-targeted potential of Leanskolin in promoting metabolic health via GLP-1 pathway activation, DPP-4 inhibition, and gut barrier support. This first report demonstrates integrated activity of this extract, offering promising insights into its therapeutic relevance for managing metabolic disorders.