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Recent clinical evidence demonstrates that berberine can significantly modulate Vascular Endothelial Growth Factor (VEGF) concentrations and improve vascular function parameters in patients with metabolic dysfunction ( 2.3.1 Comparative SAR and mitochondrial targeting of alkaloids The protoberberine alkaloids provide a fascinating paradigm of how the nitrogen oxidation state and specific ring substitutions dictate subcellular localization, pharmacokinetic profiles, and toxicity in sepsis-induced organ injury