Abstract:

An optimized formulation of milk powder containing the pepsin hydrolysate of milk casein rich in bioactive
peptides with sleep-improving and anti-fatigue functions was developed. Human feeding trails of the functional milk formula
and whole milk powder (as a control) were carried out on healthy volunteer subjects. Changes in the serum concentrations
of 38 cytokines before and after consumption were examined. The results showed that whole milk significantly stimulated
the expression levels of TNF-α, whereas the functional milk formula significantly reduced the expression levels of TNF-α,
VEGF, G-CSF, IL-17, IL-1ra and IFN-γ. To quantitatively evaluate these effects, the international authoritative database
was retrieved to query the cytokine-secreting cells and target cells to build intercellular wireless communication networks
in response to the consumption of the functional milk formula and whole milk powder. Through the directed weighted
networks, we could not only visually compare the changing levels and patterns of intercellular wireless communication
before and after the consumption of the tested materials, but also could quantitatively evaluate these changes by the outstrength(
Sout), the into-strength (Sin) and the total strength (Stotal) of the nodes, and overall network strength (Snetwork). The
network from the consumption of whole milk powder had 15 nodes and 108 edges, with an Snetwork of 34.2, showing that whole
milk plays a significant role in promoting the intercellular wireless communication network. The network from the functional milk
formula had 23 nodes and 304 edges, with an Snetwork of －885.7, showing that the functional milk formula plays a major role in
down-regulating the activity of intercellular communication network, the immune system, and the physiological and metabolic
levels, and this inhibitory effect was significantly stronger than the promoting effect of whole milk. The mathematical network
models can be used as a new method for the quantitative evaluation in vivo of functional foods.

Key words: functional milk formula, cytokines, intercellular wireless communication network, directed weighted network