PI3K/AKT signaling pathway: Molecular mechanisms and therapeutic potential in depression

Pharmacological Research, Год журнала: 2024, Номер 206, С. 107300 - 107300

Опубликована: Июль 9, 2024

Depression is a serious global mental disorder. Numerous studies have found that depression may be closely related to decreased neurogenesis, neuroinflammation, neurotransmitter imbalance, and synaptic plasticity dysfunction. The pathogenesis of complex involves multiple signal transduction pathways molecular changes. PI3K/AKT pathway an essential signaling in neurons, which widely expressed emotion-related regions the brain. Therefore, play moderating role mood disorders. However, mechanism not been fully described. This review systematically summarized discussed its potential treatment depression. will help development antidepressants.

Язык: Английский

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The Role of Brain-Derived Neurotrophic Factor as an Essential Mediator in Neuronal Functions and the Therapeutic Potential of Its Mimetics for Neuroprotection in Neurologic and Psychiatric Disorders

Molecules, Год журнала: 2025, Номер 30(4), С. 848 - 848

Опубликована: Фев. 12, 2025

Among neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4/5), BDNF has been extensively studied for its physiological role in cell survival synaptic regulation the central nervous system's (CNS's) neurons. binds to TrkB (a tyrosine kinase) with high affinity, resulting downstream intracellular signaling cascades play crucial roles determining fate, neuronal differentiation maturation of CNS It well demonstrated that downregulation/dysregulation BDNF/TrkB system is implicated pathogenesis neurologic psychiatric disorders, such as Alzheimer's disease (AD) depression. Interestingly, effects mimetic compounds flavonoids, small molecules which can activate TrkB-mediated signaling, have investigated potential therapeutic strategies brain diseases, given p75NTR, a common neurotrophin receptor, also contributes death under variety pathological conditions neurodegeneration. Since downregulation associated pathophysiology neurodegenerative diseases understanding how alterations contribute progression could provide valuable insight prevention these diseases. The present review shows recent advances molecular mechanisms underlying plasticity, providing critical insights into impact mimetics

Язык: Английский

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Autophagy: A potential target for natural products in the treatment of ulcerative colitis

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116891 - 116891

Опубликована: Июнь 12, 2024

Ulcerative colitis (UC) is a chronic inflammatory bowel disease primarily affecting the mucosa of colon and rectum. UC characterized by recurrent episodes, often necessitating lifelong medication use, imposing significant burden on patients. Current conventional advanced treatments for have disadvantages insufficient efficiency, susceptibility to drug resistance, notable adverse effects. Therefore, developing effective safe drugs has become an urgent need. Autophagy intracellular degradation process that plays important role in intestinal homeostasis. Emerging evidence suggests aberrant autophagy involved development UC, modulating can effectively alleviate experimental colitis. A growing number studies established interplay with endoplasmic reticulum stress, gut microbiota, apoptosis, NLRP3 inflammasome, all which contribute pathogenesis UC. In addition, variety epithelial cells, including absorptive goblet Paneth as well other cell types like neutrophils, antigen-presenting stem cells gut, mediate through autophagy. To date, many found natural products hold potential exert therapeutic effects regulating This review focuses possible pharmacological mechanisms target recent years, aiming provide basis new development.

Язык: Английский

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Investigating the Antidepressant Mechanisms of Polygonum sibiricum Polysaccharides via Microglial Polarization

Nutrients, Год журнала: 2024, Номер 16(3), С. 438 - 438

Опубликована: Фев. 1, 2024

Polygonum sibiricum, with its medicinal and edibility dual properties, has been widely recognized utilized throughout Chinese history. As a kind of effective component, sibiricum polysaccharides (PSP) have reported to be promising novel antidepressant agent. Meanwhile, the precise mechanisms underlying action remain elusive. The polarization state transition microglia is intricately linked neuroinflammation, indicating crucial involvement in pathophysiology depression. Researchers are vigorously pursuing exploration this potential treatment strategy, aiming comprehend mechanisms. Hence, current study was designed investigate PSP via Microglial M1/M2 Polarization, based on lipopolysaccharide (LPS)-induced BV2 cell activation model. results indicate that significantly inhibited NO LDH release reduced ROS levels LPS-induced cells. could reduce protein expression level Iba-1, decreased mRNA TNF-α, IL-1β, IL-6, increased IL-10. also CD16/32 CD206, fluorescence intensity iNOS, those Arg-1. However, pretreatment reversed alterations BDNF/TrkB/CREB Notch/Hes1 pathways These suggested exerted anti-inflammatory effects by inhibiting M1 phenotype promoting toward M2 phenotype, regulation may associated modulating pathways.

Язык: Английский

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Antidepressant Activity of Agarwood Essential Oil: A Mechanistic Study on Inflammatory and Neuroprotective Signaling Pathways

Pharmaceuticals, Год журнала: 2025, Номер 18(2), С. 255 - 255

Опубликована: Фев. 14, 2025

Background: Depression ranks among the most severe mental health conditions, and poses a burden on global health. Agarwood, an aromatic medicinal plant, has shown potential for improving symptoms. As common folk medicine, agarwood been applied as alternative method disorders such depression through aromatherapy. Previous studies have found that therapeutic effects of aromatherapy are primarily related to its volatile components. This study aimed examine antidepressant properties underlying mechanisms essential oil (AEO), collection components utilized inhalation injection administration in mice. Methods: A lipopolysaccharide (LPS)-induced inflammatory model was used evaluate AEO depression-like Behavioral assessments included open-field, tail suspension, forced swimming tests. Western blot (WB) ELISA techniques were further verify mechanistic insights. Results: In LPS-induced model, significantly improved symptoms, decreased immobility duration both suspension tests mice, reduced levels cytokines IL-1β, IL-6, TNF-α. WB experiments demonstrated inhibited NF-κB/IκB-α pathway activated BDNF/TrkB/CREB hippocampus LPS-depression Notably, extracted by hydrodistillation more effective alleviating depressive-like behaviors than using supercritical CO2 fluid extraction. Conclusions: Both exerted notable effects, potentially associated with reducing inflammation brain, downregulating NF-κB/IκB-α, upregulating neuroprotective signaling pathway. future, it is necessary determine pharmacodynamic components, key targets specific molecular AEO's so provide support research plants.

Язык: Английский

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Stimulation of microglia leads to a rapid antidepressant effect by triggering astrocytic P2Y1Rs and promoting BDNF-mediated neurogenesis in the hippocampus

Brain Behavior and Immunity, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Therapeutic Targets and Molecular Mechanisms of Calycosin in the Treatment of Depression: Insights From Chronic Mild Stress Animal Models

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(4)

Опубликована: Апрель 1, 2025

ABSTRACT Background Depression is a complex psychiatric disorder with limited therapeutic options and various side effects. Calycosin, bioactive compound derived from Astragalus membranaceus , possesses multiple pharmacological properties. This study aimed to investigate the antidepressant effects of calycosin in chronic mild stress (CMS) animal models depression elucidate its underlying mechanisms. Methods The were assessed vivo using CMS depression, including grooming frequency test, sucrose intake tail suspension open field test. Neurogenic evaluated by measuring levels BDNF, GDNF, NGF isolated hippocampus tissues. hepatoprotective liver enzyme levels. molecular mechanisms calycosin's explored vitro PC12 cells. Results Calycosin exhibited potent antidepressant‐like activities depression. Treatment significantly alleviated depressive symptoms improved neurogenic Additionally, displayed modulating enzymes vitro. are mediated stimulation TrkB–MEK–Erk1/2–CREB signaling pathway. Conclusion In conclusion, shows promise as novel agent for due diverse Further studies warranted exact targets assess efficacy safety clinical settings.

Язык: Английский

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Antidepressant-like activity of Bezafibrate in mice models of depression: a behavioral and neurobiological characterization

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 30, 2025

Depression represents a major global public health challenge, inflicting profound suffering on patients while imposing substantial socioeconomic burdens families and healthcare systems. Although monoamine-based antidepressants remain first-line pharmacotherapy, accumulating clinical evidence reveals several limitations of these medications, including delayed pharmacodynamics low remission rates. Therefore, it is necessary to search for new drugs develop effective strategies depression treatment. Bezafibrate (BEZ), which can activate proliferator-activated receptor (PPARα), exhibit various biological functions, such as improving mitochondrial function, reducing neuroinflammation, cognitive function. This study explore whether BEZ has antidepressant-like effects its potential mechanisms. The antidepressant mechanisms were assessed by using forced swim test, tail suspension sucrose preference Western blot, gene interference, immunofluorescence in the chronic unpredictable mild stress (CUMS) models depression. Results showed that treatment significantly reversed depressive behavior CUMS mice. administration obviously promoted expression PPAR, enhanced BDNF signaling pathway, hippocampal neurogenesis In addition, pharmacologcial inhibitors GW6471 K252a prevented effect BEZ. Furthermore, knockdown PPARα or AAV-PPARα-shRNA-EGFP AAV-BDNF-shRNA-EGFP, remarkably inhibit Collectively, behavioral neurobiological results demonstrate exhibits activity through PPARα/BDNF pathway may use antidepressant.

Язык: Английский

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The effect of esketamine on postoperative anxiety and depression in patients with thyroid cancer: A randomized, double-blind, placebo-controlled, parallel-group trial

Medicine, Год журнала: 2025, Номер 104(18), С. e42284 - e42284

Опубликована: Май 2, 2025

Background: This study aimed to investigate the effects of a single intravenous injection esketamine during general anesthesia on postoperative anxiety and depression in patients with thyroid cancer. Methods: In this randomized, double-blind, placebo-controlled, parallel-group trial, eighty female cancer were scheduled undergo surgery under anesthesia. The randomly divided into an group (group E) control C), 40 each group. During induction period anesthesia, E received (0.5 mg/kg), while C 0.9% sodium chloride. Zung Self-Rating Anxiety Scale Depression scores for all evaluated day before second after surgery. At same time point, venous blood was collected twice from patients, levels serum factors, such as mature brain-derived neurotrophic factor (mBDNF), 5-hydroxytryptamine (5-HT), insulin-like growth factor-1 (IGF-1), irisin, measured. Intraoperative vital signs situation recorded patients. Results: Compared C, showed significant decrease ( P < .05). increase mBDNF 5-HT .05), IGF-1 level significantly lower proportion who pump infusion vasopressors reduced Conclusion: Intravenous 0.5 mg/kg can prevent alleviate cancer, its mechanism may be related increased levels. time, hemodynamics are more stable.

Язык: Английский

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Neuroinflammation and Natural Antidepressants: Balancing Fire with Flora

Biomedicines, Год журнала: 2025, Номер 13(5), С. 1129 - 1129

Опубликована: Май 7, 2025

Background/Objectives: Major depressive disorder (MDD) is a major global health concern that intimately linked to neuroinflammation, oxidative stress, mitochondrial dysfunction, and complicated metabolic abnormalities. Traditional antidepressants frequently fall short, highlighting the urgent need for new, safer, more acceptable therapeutic techniques. Phytochemicals, i.e., natural derived from plants, are emerging as powerful plant-based therapies capable of targeting many pathogenic pathways at same time. Summary: This narrative review synthesizes evidence preclinical clinical studies on efficacy phytochemicals such curcumin, polyphenols, flavonoids, alkaloids in lowering depressed symptoms. Consistent data show these substances have neuroprotective, anti-inflammatory, antioxidant properties, altering neuroimmune interactions, reducing damage, improving resilience. Particularly, polyphenols flavonoids great potential because their capacity penetrate blood–brain barrier, inhibit cytokine activity, encourage neuroplasticity mediated by brain-derived neurotrophic factor (BDNF). Despite promising results, heterogeneity study designs, phytochemical formulations, patient demographics highlights importance thorough, standardized studies. Conclusions: identifies compelling adjuvant or independent depression treatment, providing multimodal mechanisms enhanced tolerability. Additional research into improved dosage, pharmacokinetics, long-term safety, integrative therapy approaches essential. Using phytotherapeutics could considerably improve holistic customized care, encouraging new routes neuroscience psychiatry.

Язык: Английский

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