Spirulina-derived peptide-calcium chelates: Process optimization, structural stability, and synergistic lipid regulation via host-microbiota modulation.
This study developed a novel peptide-calcium chelate (SPH-Ca) from Spirulina platensis hydrolysates with the aim of improving peptide stability and enhancing lipid-lowering activity. The chelation process was optimized by response surface methodology, yielding a calcium binding capacity of 52.9% under the optimal conditions of 60.1 °C, 40.4 min, and pH 5.1. Structural analyses using FT-IR and XRD confirmed the successful coordination of calcium ions with carboxyl and amino groups in peptides, forming a stable complex. SPH-Ca exhibited potent pancreatic lipase inhibitory activity with an IC50 of 2.02 mg/mL and functioned via a non-competitive inhibition mechanism (Ki = 0.82 mM). Notably, it retained 68.7% of its inhibitory activity after in vitro simulated gastrointestinal digestion, demonstrating significantly improved stability. In a high-fat diet-induced Caenorhabditis elegans model, SPH-Ca treatment reduced triglyceride levels by up to 75% (from 0.756 mmol/gprot in the model group to 0.195 mmol/gprot) and total cholesterol by up to 55% (from 0.795 mmol/gprot to 0.350 mmol/gprot), with 100% survival rate confirming the absence of toxicity. Further mechanistic studies in C. elegans revealed that the lipid-lowering effect was mediated through activation of the AMPK signaling pathway and modulation of gut microbiota, particularly an enrichment of Paracoccus marcusii. These findings highlight SPH-Ca as a stable and effective lipid-lowering agent with potential for further development.