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Article ; Online: Targeting autophagy and neuroinflammation pathways with plant-derived natural compounds as potential antidepressant agents.

Mokhtari, Tahmineh

2022 Volume 36, Issue 9, Page(s) 3470–3489

Abstract: Major depressive disorder (MDD) is a life-threatening disease that presents several characteristics. The pathogenesis of depression still remains poorly understood. Moreover, the mechanistic interactions of natural components in treating depression to ... ...

Abstract	Major depressive disorder (MDD) is a life-threatening disease that presents several characteristics. The pathogenesis of depression still remains poorly understood. Moreover, the mechanistic interactions of natural components in treating depression to target autophagy and neuroinflammation are yet to be evaluated. This study overviewed the effects of plant-derived natural components in regulating critical pathways, particularly neuroinflammation and autophagy, associated with depression. A list of natural components, including luteolin, apigenin, hyperforin, resveratrol, salvianolic acid b, isoliquiritin, nobiletin, andrographolide, and oridonin, have been investigated. All peer-reviewed journal articles were searched by Scopus, MEDLINE, PubMed, Web of Science, and Google Scholar using the appropriated keywords, including depression, neuroinflammation, autophagy, plant, natural components, etc. The neuroinflammation and autophagy dysfunction are critically associated with the pathophysiology of depression. Natural components with higher efficiency and lower complications can be used for targeting neuroinflammation and autophagy. These components with different doses showed the beneficial antidepressant properties in rodents. These can modulate autophagy markers, mainly AMPK, LC3II/LC3I ratio, Beclin-1. Moreover, they can regulate the NLRP3 inflammasome, resulting in the suppression of proinflammatory cytokines (e.g., IL-1β and IL-18). Future in vitro and in vivo studies are required to develop novel therapeutic approaches based on plant-derived active components to treat MDD.
MeSH term(s)	Antidepressive Agents/pharmacology ; Antidepressive Agents/therapeutic use ; Autophagy ; Depressive Disorder, Major/drug therapy ; Humans ; Inflammasomes/metabolism ; Neuroinflammatory Diseases
Chemical Substances	Antidepressive Agents ; Inflammasomes
Language	English
Publishing date	2022-07-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.7551
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Article: Targeting autophagy and neuroinflammation pathways with plant‐derived natural compounds as potential antidepressant agents

Mokhtari, Tahmineh

Phytotherapy research. 2022 Sept., v. 36, no. 9

2022

Abstract: Major depressive disorder (MDD) is a life‐threatening disease that presents several characteristics. The pathogenesis of depression still remains poorly understood. Moreover, the mechanistic interactions of natural components in treating depression to ... ...

Abstract	Major depressive disorder (MDD) is a life‐threatening disease that presents several characteristics. The pathogenesis of depression still remains poorly understood. Moreover, the mechanistic interactions of natural components in treating depression to target autophagy and neuroinflammation are yet to be evaluated. This study overviewed the effects of plant‐derived natural components in regulating critical pathways, particularly neuroinflammation and autophagy, associated with depression. A list of natural components, including luteolin, apigenin, hyperforin, resveratrol, salvianolic acid b, isoliquiritin, nobiletin, andrographolide, and oridonin, have been investigated. All peer‐reviewed journal articles were searched by Scopus, MEDLINE, PubMed, Web of Science, and Google Scholar using the appropriated keywords, including depression, neuroinflammation, autophagy, plant, natural components, etc. The neuroinflammation and autophagy dysfunction are critically associated with the pathophysiology of depression. Natural components with higher efficiency and lower complications can be used for targeting neuroinflammation and autophagy. These components with different doses showed the beneficial antidepressant properties in rodents. These can modulate autophagy markers, mainly AMPK, LC3II/LC3I ratio, Beclin‐1. Moreover, they can regulate the NLRP3 inflammasome, resulting in the suppression of proinflammatory cytokines (e.g., IL‐1β and IL‐18). Future in vitro and in vivo studies are required to develop novel therapeutic approaches based on plant‐derived active components to treat MDD.
Keywords	andrographolide ; antidepressants ; apigenin ; autophagy ; hyperforin ; inflammasomes ; interleukin-18 ; luteolin ; mental depression ; pathogenesis ; pathophysiology ; phytotherapy ; research ; resveratrol ; salvianolic acid
Language	English
Dates of publication	2022-09
Size	p. 3470-3489.
Publishing place	John Wiley & Sons, Ltd.
Document type	Article
Note	REVIEW
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.7551
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Role of NLRP3 Inflammasome in Post-Spinal-Cord-Injury Anxiety and Depression: Molecular Mechanisms and Therapeutic Implications.

Mokhtari, Tahmineh / Uludag, Kadir

ACS chemical neuroscience

2023 Volume 15, Issue 1, Page(s) 56–70

Abstract: The majority of research on the long-term effects of spinal cord injury (SCI) has primarily focused on neuropathic pain (NP), psychological issues, and sensorimotor impairments. Among SCI patients, mood disorders, such as anxiety and depression, have ... ...

Abstract	The majority of research on the long-term effects of spinal cord injury (SCI) has primarily focused on neuropathic pain (NP), psychological issues, and sensorimotor impairments. Among SCI patients, mood disorders, such as anxiety and depression, have been extensively studied. It has been found that chronic stress and NP have negative consequences and reduce the quality of life for individuals living with SCI. Our review examined both human and experimental evidence to explore the connection between mood changes following SCI and inflammatory pathways, with a specific focus on NLRP3 inflammasome signaling. We observed increased proinflammatory factors in the blood, as well as in the brain and spinal cord tissues of SCI models. The NLRP3 inflammasome plays a crucial role in various diseases by controlling the release of proinflammatory molecules like interleukin 1β (IL-1β) and IL-18. Dysregulation of the NLRP3 inflammasome in key brain regions associated with pain processing, such as the prefrontal cortex and hippocampus, contributes to the development of mood disorders following SCI. In this review, we summarized recent research on the expression and regulation of components related to NLRP3 inflammasome signaling in mood disorders following SCI. Finally, we discussed potential therapeutic approaches that target the NLRP3 inflammasome and regulate proinflammatory cytokines as a way to treat mood disorders following SCI.
MeSH term(s)	Humans ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Depression/etiology ; Depression/metabolism ; Quality of Life ; Spinal Cord Injuries/drug therapy ; Anxiety/metabolism ; Neuralgia
Chemical Substances	Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein
Language	English
Publishing date	2023-12-18
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.3c00596
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Article ; Online: Effect of using different strips on reducing the most common error in panoramic imaging: A randomised controlled trial on palatoglossal air space shadow.

Mokhtari, Andisheh / Razi, Sedigheh / Rahimipour, Kasra / Razi, Tahmineh

Journal of medical radiation sciences

2024

Abstract: Introduction: Panoramic radiography quality can be impaired by some errors such as positioning errors. Palatoglossal air space shadow error is one of the most common positioning errors and it is due to the tongue not sticking to the roof of the palate. ... ...

Abstract	Introduction: Panoramic radiography quality can be impaired by some errors such as positioning errors. Palatoglossal air space shadow error is one of the most common positioning errors and it is due to the tongue not sticking to the roof of the palate. Techniques used to deal with this error might help prevent unnecessary radiation to patients and save them time and money. The study aimed to investigate the effects of using celluloid matrix and edible tapes (fruit leather and chewing gum) on reducing the palatoglossal air space shadow error in panoramic imaging. Methods: In our study, 270 patients referred to the Department of Radiology were randomised into three groups: a control group, a celluloid matrix group and an edible tapes group. Before panoramic imaging, all patients were instructed to adhere their tongues to the roof of their mouths, with the distinction that for the celluloid matrix and edible tapes groups, patients were asked to place celluloid tapes, fruit leathers, or chewing gums on their tongues before doing so. The routine imaging process was then performed, and the results were compared across groups to evaluate the incidence of palatoglossal air space shadow error. Results: The number of error-free images in each fruit leather, chewing gum and celluloid tape group were significantly higher than the control group (all cases P < 0.05). The chances of error-free images in the fruit leather groups were the highest (9.57 times). The age (P = 0.136) and gender (P = 0.272) of patients had no significant effect on the results of interventions. Conclusion: The application of fruit leathers, chewing gums and celluloid tapes reduced the palatoglossal air space shadow error of panoramic imaging.
Language	English
Publishing date	2024-02-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2734841-6
ISSN	2051-3909 ; 2051-3909
ISSN (online)	2051-3909
ISSN	2051-3909
DOI	10.1002/jmrs.753
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Article ; Online: Stress, pain, anxiety, and depression in endometriosis-Targeting glial activation and inflammation.

Mokhtari, Tahmineh / Irandoost, Elnaz / Sheikhbahaei, Fatemeh

International immunopharmacology

2024 Volume 132, Page(s) 111942

Abstract: Endometriosis (EM) is a gynecological inflammatory disease often accompanied by stress, chronic pelvic pain (CPP), anxiety, and depression, leading to a diminished quality of life. This review aims to discuss the relationship between systemic and local ... ...

Abstract	Endometriosis (EM) is a gynecological inflammatory disease often accompanied by stress, chronic pelvic pain (CPP), anxiety, and depression, leading to a diminished quality of life. This review aims to discuss the relationship between systemic and local inflammatory responses in the central nervous system (CNS), focusing on glial dysfunctions (astrocytes and microglia) as in critical brain regions involved in emotion, cognition, pain processing, anxiety, and depression. The review presents that EM is connected to increased levels of pro-inflammatory cytokines in the circulation. Additionally, chronic stress and CPP as stressors may contribute to the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, depleting the production of inflammatory mediators in the circulatory system and the brain. The systemic cytokines cause blood-brain barrier (BBB) breakdown, activate microglia in the brain, and lead to neuroinflammation. Furthermore, CPP may induce neuronal morphological alterations in critical regions through central sensitization and the activation of glial cells. The activation of glial cells, particularly the polarization of microglia, leads to the activation of the NLRP3 inflammasome and the overproduction of inflammatory cytokines. These inflammatory cytokines interact with the signaling pathways involved in neural plasticity. Additionally, persistent inflammatory conditions in the brain lead to neuronal death, which is correlated with a reduced volume of key brain regions such as the hippocampus. This review highlights the involvement of glial cells in the pathogenesis of the mental comorbidities of EM (i.e., pain, anxiety, and depression) and to discuss potential therapeutic approaches for targeting the inflammation and activation of microglia in key brain regions.
MeSH term(s)	Humans ; Female ; Endometriosis/immunology ; Endometriosis/pathology ; Depression/immunology ; Depression/etiology ; Depression/metabolism ; Anxiety/immunology ; Animals ; Neuroglia/immunology ; Inflammation/immunology ; Stress, Psychological/immunology ; Cytokines/metabolism ; Brain/immunology ; Brain/pathology ; Brain/metabolism
Chemical Substances	Cytokines
Language	English
Publishing date	2024-04-02
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2024.111942
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Article ; Online: Corrigendum to "Potential anxiolytic and antidepressant-like effects of luteolin in a chronic constriction injury rat model of neuropathic pain: Role of oxidative stress, neurotrophins, and inflammatory factors" [Int. Immunopharmacol. 122 (2023) 110520].

Mokhtari, Tahmineh / Lu, Min / El-Kenawy, Ayman El-Meghawry

International immunopharmacology

2023 Volume 127, Page(s) 111288

Language	English
Publishing date	2023-12-23
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2023.111288
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Article ; Online: Therapeutic potential of thymoquinone and its nanoformulations in neuropsychological disorders: a comprehensive review on molecular mechanisms in preclinical studies.

Saadat, Maryam / Dahmardeh, Narjes / Sheikhbahaei, Fatemeh / Mokhtari, Tahmineh

Naunyn-Schmiedeberg's archives of pharmacology

2023

Abstract: Thymoquinone (THQ) and its nanoformulation (NFs) have emerged as promising candidates for the treatment of neurological diseases due to their diverse pharmacological properties, which include anti-inflammatory, antioxidant, and neuroprotective effects. ... ...

Abstract	Thymoquinone (THQ) and its nanoformulation (NFs) have emerged as promising candidates for the treatment of neurological diseases due to their diverse pharmacological properties, which include anti-inflammatory, antioxidant, and neuroprotective effects. In this study, we conducted an extensive search across reputable scientific websites such as PubMed, ScienceDirect, Scopus, and Google Scholar to gather relevant information. The antioxidant and anti-inflammatory properties of THQ have been observed to enhance the survival of neurons in affected areas of the brain, leading to significant improvements in behavioral and motor dysfunctions. Moreover, THQ and its NFs have demonstrated the capacity to restore antioxidant enzymes and mitigate oxidative stress. The primary mechanism underlying THQ's antioxidant effects involves the regulation of the Nrf2/HO-1 signaling pathway. Furthermore, THQ has been found to modulate key components of inflammatory signaling pathways, including toll-like receptors (TLRs), nuclear factor-κB (NF-κB), interleukin 6 (IL-6), IL-1β, and tumor necrosis factor alpha (TNFα), thereby exerting anti-inflammatory effects. This comprehensive review explores the various beneficial effects of THQ and its NFs on neurological disorders and provides insights into the underlying mechanisms involved.
Language	English
Publishing date	2023-11-27
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	121471-8
ISSN	1432-1912 ; 0028-1298
ISSN (online)	1432-1912
ISSN	0028-1298
DOI	10.1007/s00210-023-02832-8
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Article ; Online: Exogenous melatonin alleviates neuropathic pain-induced affective disorders by suppressing NF-κB/ NLRP3 pathway and apoptosis.

Mokhtari, Tahmineh / Yue, Lu-Peng / Hu, Li

Scientific reports

2023 Volume 13, Issue 1, Page(s) 2111

Abstract: In this study, we aimed to evaluate the anti-inflammatory and anti-apoptotic effects of melatonin (MLT) on neuropathic pain (NP)-induced anxiety and depression in a rat model. Adult male rats were separated into four groups, i.e., Sham-VEH: healthy ... ...

Abstract	In this study, we aimed to evaluate the anti-inflammatory and anti-apoptotic effects of melatonin (MLT) on neuropathic pain (NP)-induced anxiety and depression in a rat model. Adult male rats were separated into four groups, i.e., Sham-VEH: healthy animals received a vehicle, Sham-MLT (10 mg/kg), and chronic constrictive injury (CCI)-VEH: nerve ligation received the vehicle, and CCI-MLT. Next, we used behavioral tests to evaluate pain severity, anxiety, and depression. Finally, rats were sacrificed for molecular and histopathological studies. Behavioral tests showed that NP could induce depressive- and anxiety-like behaviors. NP activated NF-κB/NLRP3 inflammasome pathways by upregulating NF-κB, NLRP3, ASC, active Caspase-1, also enhancing the concentrations of cytokines (IL-1β and IL-18) in the prefrontal cortex (PFC) and hippocampus (HC). NP upregulated Bax, downregulated Bcl2, and increased cell apoptosis in the HC and PFC. The rats treated with MLT eliminated the effects of NP, as the reduced pain severity, improved anxiety- and depressive-like behaviors, ameliorated NF-κB/NLRP3 inflammasome pathways, and modulated levels of cytokines in the HC and PFC. MLT could promote cell survival from apoptosis by modulating Bax and Bcl2. Therefore, it might be inferred that its anti-inflammatory and anti-apoptotic properties mediate the beneficial effects of MLT in NP-induced affective disorders.
MeSH term(s)	Rats ; Male ; Animals ; NF-kappa B/metabolism ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Melatonin/pharmacology ; Melatonin/therapeutic use ; bcl-2-Associated X Protein ; Apoptosis ; Anti-Inflammatory Agents/pharmacology ; Cytokines/metabolism ; Neuralgia/drug therapy
Chemical Substances	NF-kappa B ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Melatonin (JL5DK93RCL) ; bcl-2-Associated X Protein ; Anti-Inflammatory Agents ; Cytokines ; Nlrp3 protein, rat
Language	English
Publishing date	2023-02-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-28418-1
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Article ; Online: Potential anxiolytic and antidepressant-like effects of luteolin in a chronic constriction injury rat model of neuropathic pain: Role of oxidative stress, neurotrophins, and inflammatory factors.

Mokhtari, Tahmineh / Lu, Min / El-Kenawy, Ayman El-Meghawry

International immunopharmacology

2023 Volume 122, Page(s) 110520

Abstract: This study aimed to examine the effects of luteolin (LUT) on chronic neuropathic pain (NP)-induced mood disorders (i.e., anxiety and depression) by regulating oxidative stress, neurotrophic factors (NFs), and neuroinflammation. Chronic constrictive ... ...

Abstract	This study aimed to examine the effects of luteolin (LUT) on chronic neuropathic pain (NP)-induced mood disorders (i.e., anxiety and depression) by regulating oxidative stress, neurotrophic factors (NFs), and neuroinflammation. Chronic constrictive injury (CCI) was used to induce NP in the animals. Animals in the treatment groups received LUT in three doses of 10, 25, and 50 mg/kg for 21 days. The severity of pain and mood disorders were examined. Finally, animals were sacrificed, and their brain tissue was used for molecular and histopathological studies. CCI led to cold allodynia and thermal hyperalgesia. Mood alterations were proven in the CCI group, according to the behavioral tests. Levels of glial cell-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), B-cell lymphoma-2 (Bcl2), superoxide dismutase (SOD), catalase (CAT), and nuclear factor erythroid-2-related factor 2 (Nrf2) were reduced in the hippocampus (HPC) and prefrontal cortex (PFC). Furthermore, the levels of MDA, Bcl-2-associated X protein (Bax), and inflammatory markers, including nuclear factor kappa B (NF-κB), NLR family pyrin domain containing 3 (NLRP3), interleukin-1β (IL-1β), IL-18, IL-6, and tumor necrosis factor-α (TNF-α) significantly increased in the HPC and PFC following CCI induction. LUT treatment reversed the behavioral alterations via regulation of oxidative stress, neurotrophines, and inflammatory mediators in the HPC and PFC. Findings confirmed the potency of LUT in the improvement of chronic pain-induced anxiety- and depressive-like symptoms, probably through antioxidant, anti-inflammatory, and neuroprotective properties in the HPC and PFC.
MeSH term(s)	Rats ; Animals ; Anti-Anxiety Agents/pharmacology ; Anti-Anxiety Agents/therapeutic use ; Luteolin/pharmacology ; Luteolin/therapeutic use ; Nerve Growth Factors/metabolism ; Constriction ; Antidepressive Agents/therapeutic use ; Oxidative Stress ; NF-kappa B/metabolism ; Hyperalgesia/drug therapy ; Hyperalgesia/pathology ; Neuralgia/drug therapy ; Neuralgia/pathology
Chemical Substances	Anti-Anxiety Agents ; Luteolin (KUX1ZNC9J2) ; Nerve Growth Factors ; Antidepressive Agents ; NF-kappa B
Language	English
Publishing date	2023-07-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2023.110520
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Article ; Online: Exogenous melatonin alleviates neuropathic pain-induced affective disorders by suppressing NF-κB/ NLRP3 pathway and apoptosis

Tahmineh Mokhtari / Lu-Peng Yue / Li Hu

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 15

Abstract: Abstract In this study, we aimed to evaluate the anti-inflammatory and anti-apoptotic effects of melatonin (MLT) on neuropathic pain (NP)-induced anxiety and depression in a rat model. Adult male rats were separated into four groups, i.e., Sham-VEH: ... ...

Abstract	Abstract In this study, we aimed to evaluate the anti-inflammatory and anti-apoptotic effects of melatonin (MLT) on neuropathic pain (NP)-induced anxiety and depression in a rat model. Adult male rats were separated into four groups, i.e., Sham-VEH: healthy animals received a vehicle, Sham-MLT (10 mg/kg), and chronic constrictive injury (CCI)-VEH: nerve ligation received the vehicle, and CCI-MLT. Next, we used behavioral tests to evaluate pain severity, anxiety, and depression. Finally, rats were sacrificed for molecular and histopathological studies. Behavioral tests showed that NP could induce depressive- and anxiety-like behaviors. NP activated NF-κB/NLRP3 inflammasome pathways by upregulating NF-κB, NLRP3, ASC, active Caspase-1, also enhancing the concentrations of cytokines (IL-1β and IL-18) in the prefrontal cortex (PFC) and hippocampus (HC). NP upregulated Bax, downregulated Bcl2, and increased cell apoptosis in the HC and PFC. The rats treated with MLT eliminated the effects of NP, as the reduced pain severity, improved anxiety- and depressive-like behaviors, ameliorated NF-κB/NLRP3 inflammasome pathways, and modulated levels of cytokines in the HC and PFC. MLT could promote cell survival from apoptosis by modulating Bax and Bcl2. Therefore, it might be inferred that its anti-inflammatory and anti-apoptotic properties mediate the beneficial effects of MLT in NP-induced affective disorders.
Keywords	Medicine ; R ; Science ; Q
Subject code	150
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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