Andrographolide (Compound 10), the bitter diterpene lactone, at 7.5 and 15 mg/kg exerted an anti-colitis and anti-tumor effect by lowering the expression of cleaved CASP1, IL-1β, and mitochondrial membrane potential collapse via the PIK3CA–AKT1–MTOR–RPS6KB1 pathway. Here, CASP1 is linked to colitis.