A Combination of Psidium guajava and Seriphium plumosum Modulates Glucose Metabolism and Reduces Hepatic GLUT2 Expression Through Additive-to-Synergistic Interactions
Abstract
Background: Type 2 diabetes mellitus (T2DM) remains a major global health challenge, prompting interest in plant-based interventions with multi-target metabolic effects. This study evaluated the individual and combined effects of Psidium guajava (PG) and Seriphium plumosum (SP) on hepatic and skeletal muscle glucose metabolism. Methods: HepG2 hepatocytes and differentiated C2C12 myotubes were treated with PG, SP, and a 1:1 PG+SP combination. Cell viability, glucose uptake, GLUT2 expression, glycogen content, and AMP levels were assessed. Interactions were evaluated using Bliss Independence, Combination Index (CI), Loewe Additivity, and Zero Interaction Potency (ZIP) models. Results: SP exhibited minimal cytotoxicity, whereas PG induced concentration-dependent reductions in HepG2 viability. The PG+SP combination maintained higher viability than PG alone and demonstrated additive-to-synergistic interactions (CI = 0.51-0.89). In HepG2 cells, all treatments significantly enhanced glucose uptake relative to controls (p p p Conclusions: The PG+SP combination co-ordinately modulated glucose uptake, glycogen storage, GLUT2 expression, and AMP-related energy status across hepatic and skeletal muscle models. These findings provide mechanistic support for further investigation of this botanical combination as a potential multi-target strategy for T2DM and metabolic dysfunction.
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