Investigation and comparison of the protective activities of three functional proteins-lactoferrin, α-lactalbumin, and β-lactoglobulin-in cerebral ischemia reperfusion injury

J Dairy Sci. 2020 Jun;103(6):4895-4906. doi: 10.3168/jds.2019-17725. Epub 2020 Mar 27.

Abstract

The objective of this study was to evaluate the protection conferred by lactoferrin, α-lactalbumin, and β-lactoglobulin in cerebral ischemia reperfusion (I/R) injury. Rat pheochromocytoma (PC12) cells were used to construct an oxygen and glucose deprivation model in vitro, and ICR mice underwent carotid artery "ligation-relaxation" to construct a cerebral I/R injury model in vivo. The levels of toll-like receptor 4 (TLR4) and downstream factors including nuclear factor-κB, tumor necrosis factor-α, and IL-1β were measured. Metabonomics detection and data mining were conducted to identify the specific metabolic sponsor of the 3 proteins. The results showed that lactoferrin, α-lactalbumin, and β-lactoglobulin protected neurons from cerebral I/R injury by increasing the level of bopindolol and subsequently inhibiting the TLR4-related pathway to different degrees; β-lactoglobulin had the strongest activity of the 3 proteins. In summary, this study is the first to investigate and compare the protective effects of lactoferrin, α-lactalbumin, and β-lactoglobulin in a cerebral stroke model. The results implicate TLR4 as a novel target of the 3 bioactive proteins to prevent cerebral I/R injury.

Keywords: cerebral ischemia reperfusion; lactoferrin; toll-like receptor 4; α-lactalbumin; β-lactoglobulin.

MeSH terms

  • Animals
  • Glucose / metabolism
  • Interleukin-1beta / metabolism
  • Lactalbumin / metabolism
  • Lactalbumin / therapeutic use*
  • Lactoferrin / metabolism
  • Lactoferrin / therapeutic use*
  • Lactoglobulins / metabolism
  • Lactoglobulins / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / metabolism
  • Oxygen / metabolism
  • PC12 Cells
  • Rats
  • Reperfusion Injury / prevention & control*
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1beta
  • Lactoglobulins
  • NF-kappa B
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Lactalbumin
  • Lactoferrin
  • Glucose
  • Oxygen