Adaptogens in Long-Lasting Brain Fatigue: An Insight from Systems Biology and Network Pharmacology

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 261 - 261

Published: Feb. 15, 2025

Long-lasting brain fatigue is a consequence of stroke or traumatic injury associated with emotional, psychological, and physical overload, distress in hypertension, atherosclerosis, viral infection, aging-related chronic low-grade inflammatory disorders. The pathogenesis linked to disrupted neurotransmission, the glutamate-glutamine cycle imbalance, glucose metabolism, ATP energy supply, which are multiple molecular targets signaling pathways neuroendocrine-immune blood circulation systems. Regeneration damaged tissue long-lasting multistage process, including spontaneously regulating hypothalamus-pituitary (HPA) axis-controlled anabolic-catabolic homeostasis recover harmonized sympathoadrenal system (SAS)-mediated function, deregulated gene expression rehabilitation. driving mechanism spontaneous recovery regeneration cross-talk mediators neuronal, microglia, immunocompetent, endothelial cells collectively involved neurogenesis angiogenesis, plant adaptogens can target. Adaptogens small molecules origin that increase adaptability organisms stress by interaction HPA axis SAS (neuroendocrine-immune cardiovascular complex), targeting adaptive GPCR pathways. Two major groups comprise (i) phenolic phenethyl phenylpropanoid derivatives (ii) tetracyclic pentacyclic glycosides, whose chemical structure be distinguished as related correspondingly monoamine neurotransmitters (epinephrine, norepinephrine, dopamine) steroid hormones (cortisol, testosterone, estradiol). In this narrative review, we discuss multitarget integrated pharmacological activity botanical ischemic stroke, fatigue; time-dependent dual response physiological regulatory systems support overload; (iii) dose-dependent reversal (hormetic) effect adaptogens. This review shows adaptogenic concept cannot reduced rectified various effects on selected specific modes action without estimating their interactions within networks complex that, turn, regulates other (cardiovascular, gastrointestinal, reproductive systems) due numerous intra- extracellular communications feedback regulations. These result polyvalent pleiotropic adaptogens, essential for characterizing distinct types botanicals. They trigger defense leads extension limits resilience inducing mental For first time, justifies potential particularly hybrid preparation (BHP) Arctic Root Ashwagandha, providing rationale use individuals experiencing fatigue. provided insight into future research network pharmacology preventing rehabilitating following trauma, infections.

Language: Английский

Signaling by latrophilin adhesion-GPCRs in synapse assembly

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Synaptic Gα12/13 signaling establishes hippocampal PV inhibitory circuits

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(52)

Published: Dec. 18, 2024

Combinatorial networks of cell adhesion molecules and surface receptors drive fundamental aspects neural circuit establishment function. However, the intracellular signals orchestrated by these complexes remain less understood. Here, we report that Gα12/13 pathway lies downstream several GPCRs with critical synaptic functions. Impairment in postnatal hippocampal neurons diminishes inhibitory inputs without altering neuronal morphology or excitatory transmission. signaling CA1 vivo selectively regulates PV interneuron connectivity, supporting an synapse subtype-specific function this pathway. Our studies establish as a node shapes circuitry.

Language: Английский