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Global Translational Medicine Traumatic memories in PTSD

Table 1. A summary of the natural inhibitors of PDK-1 and foods that contain these active ingredients
PDK1 inhibitor Mechanism of action Plant References
Kaempferol GSK-3β inhibitor Fruits, vegetables, and herbs 113
Quercetin Reduces lipid peroxidation Onions, kale, and broccoli 114
Myricetin Anticancer, antidiabetic, and antiobesity and Oranges, berries, tomatoes, nuts, and tea 115
cardiovascular protection
Epigallocatechin-3 gallate Immunoregulation and neuroprotection Green tea 116
Lupiwighteone isoflavone Cell cycle arrest and apoptosis and activates the Glycyrrhiza glabra; Lotus pedunculatus 117
Nrf2/ARE pathway
Delphinidin Antiangiogenic activities Citrus fruits 118
Honokiol Antidepressant and antitumorigenic Cherries, berries, and grapes 119
Rutin Reduces the formation of reactive oxygen Oranges, lemons, grapes, peaches, limes, 120
species and buckwheat

some individuals develop PTSD while others do not presence of mitochondrial DNA (mtDNA) in the cardiac
(vulnerability quantification). A recent study strictly circulation. 135
explored this aspect in veterans with war-related and Mitochondrial transplantation for rescuing neurons
unrelated stressors and demonstrated that cf-mtDNA from apoptosis or ferroptosis is now possible and was
levels reflect glucocorticoid sensitivity in individuals with performed successfully in both animals and humans.
PTSD, a measure of susceptibility. 130 Nevertheless, to the best of our knowledge, it has not been
Altogether, mitochondria serve as more than just attempted as a treatment for mental illness. 136
energy-producing batteries; their involvement in stress Rescuing the mitochondrion using MLR, kaempferol,
places them at the interface of biological and psychological and berberine is a strategy to prevent GSK-3β overactivation
stressors.
by toxic ceramides, oxysterols, or oxidized phospholipids.
As a former bacterium, the mitochondrion has Moreover, serotonin reuptake inhibitors (SSRIs) facilitate
retained the ability to communicate with intestinal mitochondrial transfer, emphasizing potential strategies
microbes, contributing to the gut–brain axis. For instance, for restoring neurometabolic homeostasis in SMI and
metabolites produced by gut microbes interact directly neurodegeneration.
with mitochondria in the brain, regulating their function.
In this regard, short-chain fatty acids by the gut microbiota 6.2. Mitochondrial transfer
cross the BBB, influencing the mitochondria and alleviating Under physiological or pathological conditions,
the symptoms of depression. 131 intercellular mitochondrial transfer can occur via tunneling
Mitochondria contain GSK-3β, a kinase implicated in nanotubes (TNTs) or extracellular vesicles (EVs).
SMI, including PTSD. Lithium, berberine, and kaempferol Non-canonical mitochondrial transfer can occur
inhibit the activity of GSK-3 β, thereby decreasing the through cell–cell fusion, synaptosomes, or dendritic
risk of death of the organelle. Furthermore, the transfer of networks. Cell–cell fusion can occur in senescent neurons
mitochondria from astrocytes to neurons ensures energy that reenter the cell cycle but cannot complete replication,
availability in the CNS. remaining indefinitely in a fused state.

6.1. Mitochondrial transplantation Besides its role in the intracellular compartment, a
growing body of evidence indicates that under physiological
Mitochondrial transplantation experiments started in the or pathological conditions, mitochondria can be secreted
1980s when naked organelles were coincubated with various
cell types to facilitate internalization. Using originally into the extracellular space, where they play a vital role in
132
137
HeLa cells and mesenchymal stem cells as mitochondrial regulating metabolism or immunity.
sources, this transplantation technique took 1 – 2 h to Pre-clinical research has shown that mitochondrial
supply organelles to the target, mitochondria-depleted transplantation decreases LPS-induced depression,
cells. 133,134 Successful mitochondrial transplantation is indicating its possible therapeutic application for PTSD or
138
currently possible on several cell types, and for instance, major depressive disorder (MDD). Antidepressant drugs
on cardiomyocytes, which can be confirmed by the belonging to the SSRI category improve mitochondrial

Volume 3 Issue 4 (2024) 8 doi: 10.36922/gtm.3974