Abstract

Background Amidst the rising global prevalence of diabetes, exploring novel anti-diabetic agents remains a crucial 
endeavor. This study investigated the biochemical mechanism of action of a poly-herbal formulation (PHF5) on 
HepG2 cell lines as well as molecular interactions between bioactive compounds of PHF5 and PKB/Akt, AMPK. PHF5 
was formulated from leaves of Ocimum gratissimum, Vernonia amygdalina, Gongronema latifolium, Gnetum africanum, 
and Aloe barbadensis.
Method The study employed an experimental design encompassing both in vitro and in silico analysis. HepG2 
cells were treated with PHF5 in in vitro studies that looked at parameters like cell viability, glucose uptake, and lipid 
accumulation. Also, glycation and fructosamine formation were studied in bovine serum albumin (BSA) that had been 
exposed to fructose and PHF5. In silico investigations utilized virtual screening and molecular docking simulations to 
elucidate the interactions of phytochemicals from PHF5 with key target enzymes involved in glucose metabolism.
Results It was found that PHF5 contained key phenolics such as quercetic, rutin etc. through HPLC profiling. In 
silico modeling demonstrated favorable binding of rutin and quercetin in PHF5 to PKB/Akt and AMPK, key proteins 
involved in glucose metabolism. The finding here suggests an antidiabetic action of PHF5, which is mediated via 
activation of the P13K/Akt pathway leading to trafficking of GLUT4 and simulation of insulin secretion. The findings 
also revealed significant enhancements in cell viability and glucose uptake, coupled with reduced lipid accumulation 
in HepG2 cells following treatment with PHF5. Additionally, PHF5 demonstrated a mitigating effect on glycation and 
fructosamine formation.
Conclusion This study sheds light on the diverse phytochemical composition of PHF5, highlighting potential 
interactions with crucial enzymes involved in glucose metabolism. The observed promising outcomes points at the 
potential of PHF5 as a valuable anti-diabetic agent.