Subtitle: Bridging Traditional Phytochemistry and Modern Peptidomics for Functional Food Innovation

Once overshadowed by polysaccharides and saponins, bioactive peptides from Polygonatum are emerging as potent, targeted antioxidants with significant potential for functional foods and health supplements, validated by cutting-edge mass spectrometry and cellular studies.

For millennia, species of Polygonatum, known as Solomon’s Seal or Yellow Essence in traditional medicine, have been revered for their health-promoting properties. While modern research has long focused on its polysaccharides and saponins, a new frontier is being unlocked: Polygonatum peptides. Advanced peptidomics is now revealing that this medicinal herb harbors a rich repository of short-chain amino acid sequences with potent and specific bioactivities. These peptides, particularly from Polygonatum cyrtonema Hua, represent a paradigm shift—from broad-spectrum herbal extracts to precision bioactive molecules capable of interacting with cellular pathways to combat oxidative stress, a root cause of aging and chronic disease.

Scientific Characterization: From Endogenous Signals to Engineered Hydrolysates

The study of Polygonatum peptides involves two primary classes, each with distinct origins and implications:

• Endogenous Peptides: The Plant’s Native Toolkit
  These are short peptides naturally present within the plant tissue, produced by the plant’s own proteolytic systems. A landmark 2024 study utilized nano-LC-Q Exactive Plus mass spectrometry to perform an extensive characterization of these peptides in P. cyrtonema, identifying 2,571 unique endogenous peptide sequences. A key finding was that over 60% of these native peptides are very short, consisting of 4 to 6 amino acids. This small size is crucial, as bioinformatics and molecular docking analyses predicted that these shorter endogenous peptides possess significantly higher antioxidant potential than their longer counterparts, likely due to better bioavailability and interaction with molecular targets.
• Exogenous (Hydrolysate) Peptides: Unlocking Latent Potential
  This category involves peptides created by enzymatically breaking down (“hydrolyzing”) the larger storage proteins within Polygonatum. This process mimics digestion and is designed to liberate encrypted bioactive fragments that are not active in the parent protein. Research has optimized this hydrolysis to maximize antioxidant yield. Subsequent separation and identification work has successfully isolated and characterized specific antioxidant peptide sequences from these hydrolysates, marking a significant step from complex mixtures to defined actives.

The table below summarizes key bioactive peptides identified from Polygonatum cyrtonema Hua:

Biological Activities and Functional Food Applications

The primary and most compelling bioactivity documented for Polygonatum peptides is potent antioxidant capacity. Oxidative stress, resulting from an imbalance between free radicals and antioxidants, is implicated in cellular aging, inflammation, and numerous chronic conditions. Polygonatum peptides address this via multiple mechanisms:

1. Direct Free Radical Scavenging: In vitro assays demonstrate that purified peptide fractions from Polygonatum hydrolysates exhibit significant free radical scavenging rates, such as a 30.1% scavenging rate against ABTS⁺ radicals.
2. Cellular Protection: The most direct evidence comes from cell culture studies. The identified tripeptides QFLPF, FVPF, and FPNLF were tested on human HepG2 liver cells subjected to oxidative damage. At a concentration of 100 μg/mL, these peptides increased cell viability by 6.39%, 14.51%, and 9.98% respectively, compared to damaged cells not treated with the peptides. This proves a tangible cytoprotective effect.
3. Synergy with Traditional Use: These mechanisms provide a modern molecular explanation for the traditional use of Polygonatum in combating fatigue and supporting liver health. By protecting cells from oxidative damage, the peptides contribute to enhanced cellular resilience and function.

This robust scientific backing positions Polygonatum peptides perfectly for the functional food and nutraceutical market. They can be developed as:

• Core ingredients in dietary supplements targeting anti-aging, liver health, and overall vitality.
• Natural preservatives and functional additives in health foods and beverages, leveraging their antioxidant properties for both product stability and consumer health benefits.
• Precision nutrients in medical foods designed for conditions associated with high oxidative stress.

Future Outlook and Research Trajectory

The exploration of Polygonatum peptides is transitioning from discovery to application and deepening mechanistic understanding. The field is moving towards harnessing these valuable functional ingredients for disease prevention and health promotion.

Key future directions include:

• Mechanistic Deep Dive: While antioxidant activity is established, research must elucidate the exact signaling pathways involved (e.g., Keap1-Nrf2) and explore other potential bioactivities such as immunomodulation or metabolic regulation.
• Human Clinical Trials: Translating promising in vitro and cellular results into validated human health outcomes through rigorous clinical studies is the essential next step.
• Sustainable Production Optimization: Improving extraction and enzymatic hydrolysis protocols to enhance yield, potency, and economic viability for large-scale production. Research into the unique bioactive potential of different Polygonatum species also remains an open avenue.