Curcumin Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors via Restoring Changes in Oxidative Stress and the Activation of Nrf2 Signaling Pathway in Rats

Liao, Dehua; Lv, Chuanfeng; Cao, Lizhi; Yao, Dunwu; Wu, Yi; Long, Manmei; Liu, Geoffrey; Jiang, Pei

doi:10.1155/2020/9268083

Cited by 77 publications

(68 citation statements)

References 61 publications

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“…19 Furthermore, our results are in line with previous studies indicating the downregulation of both Nrf2 and its downstream protein HO-1 in a depression model. 61 Interestingly, increased levels of ROS and LPO, along with the downregulation of Nrf2/HO-1, were markedly recovered in carvacrol-treated animals, validating our proposed hypothesis that carvacrol exerts free-radical scavenging and antioxidant activity. We previously reported the antioxidant effect of a similar monoterpene carveol in ischemic stroke by targeting the Nrf2.…”

supporting

confidence: 80%

Natural Dietary Supplement, Carvacrol, Alleviates LPS-Induced Oxidative Stress, Neurodegeneration, and Depressive-Like Behaviors via the Nrf2/HO-1 Pathway

Naeem¹,

Kury²,

Nasar³

et al. 2021

JIR

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Major depressive disorder (MDD) is a debilitating human health condition characterized by mood swings and is associated with a high probability of suicide attempts. Several studies have reported a role of neuroinflammation in MMD, yet the efficacy of natural drug substances on neuroinflammation-associated depression has not been wellinvestigated. The present study examined the neuroprotective effects of carvacrol on lipopolysaccharide (LPS)-induced neuroinflammation, depression, and anxiety-like behavior. Methods: Male Sprague Dawley rats were divided into two experimental cohorts to determine the effects and the effective dose of carvacrol (whether 20 mg/kg or 50 mg/kg), and further demonstrate the mechanism of action of nuclear factor E2-related factor (Nrf2) in depression. Results: We found marked neuronal alterations in the cortex and hippocampus of LPSintoxicated animals that were associated with higher inflammatory cytokine expression such as cyclooxygenase (COX2), tumor necrosis factor-alpha (TNF-α), and c-Jun N-terminal kinase (p-JNK). These detrimental effects exacerbated oxidative stress, as documented by a compromised antioxidant system due to high lipid peroxidase (LPO). Carvacrol (20 mg/kg) significantly reverted these changes by positively modulating the antioxidant gene Nrf2, a master regulator of the downstream antioxidant pathway. To further investigate the role of Nrf2, an inhibitor of Nrf2 called all-trans retinoic acid (ATRA) was used, which further exacerbated LPS toxicity with a higher oxidative and inflammatory cytokine level. To further support our notion, we performed virtual docking of carvacrol with the Nrf2-Keap1 target and the resultant drug-protein interactions validated the in vivo findings. Conclusion: Collectively, our findings suggest that carvacrol (20 mg/kg) could activate the endogenous master antioxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating LPS-induced neuroinflammation and neurodegeneration.

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supporting

confidence: 80%

Natural Dietary Supplement, Carvacrol, Alleviates LPS-Induced Oxidative Stress, Neurodegeneration, and Depressive-Like Behaviors via the Nrf2/HO-1 Pathway

Naeem¹,

Kury²,

Nasar³

et al. 2021

JIR

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“…Inhibition of CaMKIIβ-ERK1/2-CREB signaling mediates the chronic ketamine use-associated cognitive impairments by restraining synaptic signaling ( Luo et al, 2020 ). Supplementation of curcumin increases the ratio of pCREB to CREB and corrects the depressive-like behaviors successfully in CUS-treated rats ( Liao et al, 2020 ). CREB signaling, which is inhibited by over-activated GluN2B, participates in the antidepressant-like effects of ketamine, and extrasynaptic CaMKIIα is also involved in the CREB signaling.…”

Section: Discussionmentioning

confidence: 99%

Latent Sex Differences in CaMKII-nNOS Signaling That Underlie Antidepressant-Like Effects of Yueju-Ganmaidazao Decoction in the Hippocampus

Yin

Qian

Chen

et al. 2021

Front. Behav. Neurosci.

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Previous studies have demonstrated that Yueju-Ganmaidazao (YG) decoction induces rapid antidepressant-like effects, and the antidepressant response is mostly dependent on the suppression of nitric oxide-cyclic guanosine monophosphate signaling in male mice. This study aimed to investigate the sex difference mediated by calcium/calmodulin-dependent protein kinase II (CaMKII)-neuronal nitric oxide synthase (nNOS) signaling involved in the antidepressant-like effect of YG in mice. We found that the immobility times in the tail suspension test (TST) were found to be decreased after the single injection of YG in male and female mice with the same dosage. Additionally, chronic administration for 4 days of subthreshold dosage of YG and escitalopram (ES) also significantly decreased the immobility time in mice of both sexes. Chronic subthreshold dosage of YG and ES in LPS-treated mice and in chronic unpredictable stress (CUS) mice both decreased the immobility time, which was increased by stress. Meanwhile, in CUS-treated mice, sucrose preference test, forced swimming test, and open field test were applied to further confirm the antidepressant-like effects of YG and ES. Moreover, CUS significantly decreased the expression of nNOS and CaMKII, and both YG and ES could enhance the expression in the hippocampus of female mice, which was opposite to that in male mice, while endothelial nitric oxide synthase expression was not affected by stress or drug treatment neither in male mice nor in female mice. Finally, subthreshold dosage of YG combined with 7-nitroindazole (nNOS inhibitor) induced the antidepressant-like effects both in female and in male mice, while the single use of YG or 7-NI did not display any effect. However, pretreatment with KN-93 (CaMKII inhibitor) only blocked the antidepressant-like effect of high-dosage YG in female mice. Meanwhile, in CUS mice, chronic stress caused NR1 overexpression and inhibited cAMP response element binding protein action, which were both reversed by YG and ES in male and female mice, implying that YG and ES produced the same antidepressant-like effect in mice of both sexes. The study revealed that chronic treatment with a subthreshold dose of YG also produced antidepressant-like effects in female mice, and these effects depended on the regulation of the CaMKII-nNOS signaling pathway.

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“…For example, it has been shown that HO-1 has proproliferative effects in endothelial cells and some tumor cells, while the antiproliferative effects in vascular and airway smooth muscle cells have also been proven [44][45][46][47]. NQO-1 and HO-1 are important antioxidant enzymes in the Nrf2-ARE pathway, and NQO-1 regulates the cellular stress response by reducing quinone [48,49]. Normally, Nrf2 is located in the cytoplasm and translocates into the nucleus after stimulation.…”

Section: Discussionmentioning

confidence: 99%

Study of the Mechanism by Which Curcumin Cooperates with Sestrin2 to Inhibit the Growth of Pancreatic Cancer

et al. 2021

Gastroenterology Research and Practice

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Background. Pancreatic carcinoma is a malignant tumor with a high fatality rate, and the increased resistance of pancreatic carcinoma to chemotherapy has become a difficult problem in clinical practice. Hence, it is imperative to develop an effective treatment for pancreatic cancer. Sestrins are a class of stress-induced proteins that have antioxidation functions, regulating cell growth and metabolism. Curcumin is a natural pigment isolated from turmeric. Several studies have also suggested that this molecule has multiple pharmacological effects, such as anti-inflammatory, antioxidant, and antitumor effects. However, there are insufficient studies on curcumin cooperating with the sestrin family to inhibit tumors, and the mechanism is still unclear. Our aim was to observe the potential anticancer effects of curcumin combined with the sestrin family on pancreatic carcinoma and probe its possible molecular mechanisms. Methods. Lentiviral infection, real-time fluorescence quantitative PCR assays, Cell Counting Kit-8 assays, real-time cell analysis technology, colony formation assays, wound healing assays, Transwell invasion assays, protein extraction, and western blots (WBs) were used to evaluate the effect of curcumin combined with sestrin2 on the proliferation, invasion, and migration of pancreatic carcinoma cells. Results. The results revealed that curcumin cooperated with sestrin2 to significantly suppress pancreatic cancer. In addition, we determined that sestrin2 cooperated with curcumin to inhibit pancreatic cancer by specifically targeting Nrf2/Keap1/HO-1/NQO-1. Conclusion. These findings clarify that curcumin-mediated synergistic targeting of sestrin2 is a potentially valuable treatment for pancreatic cancer.

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Curcumin Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors via Restoring Changes in Oxidative Stress and the Activation of Nrf2 Signaling Pathway in Rats

Cited by 77 publications

References 61 publications

Natural Dietary Supplement, Carvacrol, Alleviates LPS-Induced Oxidative Stress, Neurodegeneration, and Depressive-Like Behaviors via the Nrf2/HO-1 Pathway

Natural Dietary Supplement, Carvacrol, Alleviates LPS-Induced Oxidative Stress, Neurodegeneration, and Depressive-Like Behaviors via the Nrf2/HO-1 Pathway

Latent Sex Differences in CaMKII-nNOS Signaling That Underlie Antidepressant-Like Effects of Yueju-Ganmaidazao Decoction in the Hippocampus

Study of the Mechanism by Which Curcumin Cooperates with Sestrin2 to Inhibit the Growth of Pancreatic Cancer

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