Naringin Targets NFKB1 to Alleviate Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in PC12 Cells Via

Wei Cao1, She-Jun Feng2, Min-Chen Kan3

  • 1Neurology Ward 3, Affiliated Hospital of Hebei University, Baoding, 071000, Hebei, China.

Insights

Naringin protects PC12 cells from oxygen-glucose deprivation/reoxygenation injury by targeting NFKB1. This flavonoid promotes cell proliferation and reduces apoptosis by regulating NFKB1, reactive oxygen species, and the HIF-1α/AKT/mTOR pathway.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cell Biology

Background:

  • Cerebral ischemia-reperfusion (I/R) injury is a significant cause of neurological damage.
  • Oxygen-glucose deprivation/reoxygenation (OGD/R) is a common in vitro model to study I/R injury.
  • Naringin, a natural flavonoid, has shown potential therapeutic effects, but its mechanism in I/R injury requires elucidation.

Purpose of the Study:

  • To investigate the protective effects of naringin against OGD/R-induced injury in PC12 cells.
  • To identify the molecular targets and signaling pathways involved in naringin's mechanism of action.
  • To explore the role of NFKB1 in OGD/R injury and its interaction with naringin.

Main Methods:

  • Bioinformatics analysis to identify naringin's target gene and pathways.
  • Establishment of an OGD/R model using PC12 cells.
  • Assessment of cell proliferation (CCK-8) and apoptosis (flow cytometry).
  • Measurement of NFKB1 expression (qRT-PCR), protein levels (Western blot), and reactive oxygen species (ROS) (DCF-DA kit).

Main Results:

  • NFKB1 was identified as a target gene of naringin and was upregulated in OGD/R-treated cells.
  • Naringin alleviated OGD/R-induced injury by increasing cell proliferation and decreasing apoptosis.
  • Naringin regulated NFKB1 expression, apoptosis-associated proteins, and ROS levels.
  • NFKB1 depletion enhanced naringin's protective effects and modulated apoptosis.
  • Naringin and NFKB1 depletion upregulated HIF-1α, p-AKT, and p-mTOR, suggesting activation of the HIF-1α/AKT/mTOR pathway.

Conclusions:

  • Naringin exerts neuroprotective effects against OGD/R-induced injury in PC12 cells.
  • The mechanism involves targeting NFKB1 and modulating the HIF-1α/AKT/mTOR signaling pathway.
  • Naringin's ability to regulate NFKB1, apoptosis, ROS, and key pathway proteins offers potential for treating cerebral I/R injury.

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
9.7K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.2K
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
2.2K
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.9K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K