3,5,6,7,8,3′,4′-Heptamethoxyflavone Ameliorates Depressive-Like Behavior and Hippocampal Neurochemical Changes in Chronic Unpredictable Mild Stressed Mice by Regulating the Brain-Derived Neurotrophic Factor: Requirement for ERK Activation

Sawamoto, Atsushi; Okuyama, Satoshi; Amakura, Yoshiaki; Yoshimura, Manabu; Yamada, Takashi; Yokogoshi, Hidehiko; Nakajima, Miki; Furukawa, Yoshiko

doi:10.3390/ijms18102133

Cited by 39 publications

(24 citation statements)

References 45 publications

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“…Truth be told, it has as of late been exhibited that orally administered 3,5,6,7,8,3′,4′-heptamethoxyflavone (9) is beneficial for the upregulation of BDNF in the hippocampus via the ERK1/2/MAP system. These information ought to be identified with the antidepressant effects of this compound [ 147 ].…”

Section: Resultsmentioning

confidence: 99%

Antidepressant Flavonoids and Their Relationship with Oxidative Stress

Hrițcu

Ionita

Postu

et al. 2017

Oxidative Medicine and Cellular Longevity

102

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Depression is a serious disorder that affects hundreds of millions of people around the world and causes poor quality of life, problem behaviors, and limitations in activities of daily living. Therefore, the search for new therapeutic options is of high interest and growth. Research on the relationship between depression and oxidative stress has shown important biochemical aspects in the development of this disease. Flavonoids are a class of natural products that exhibit several pharmacological properties, including antidepressant-like activity, and affects various physiological and biochemical functions in the body. Studies show the clinical potential of antioxidant flavonoids in treating depressive disorders and strongly suggest that these natural products are interesting prototype compounds in the study of new antidepressant drugs. So, this review will summarize the chemical and pharmacological perspectives related to the discovery of flavonoids with antidepressant activity. The mechanisms of action of these compounds are also discussed, including their actions on oxidative stress relating to depression.

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Section: Resultsmentioning

confidence: 99%

Antidepressant Flavonoids and Their Relationship with Oxidative Stress

Hrițcu

Ionita

Postu

et al. 2017

Oxidative Medicine and Cellular Longevity

102

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“…BDNF is the most widely-distributed neurotrophic factor in the central nervous system and, importantly, activated CREB directly regulates the transcription of BDNF [ 38 ]. Increased expression of BDNF in the hippocampus and cortex produces an antidepressant-like effect in both corticosterone and chronic unpredictable mild stress-induced depression-like animal models [ 39 ]. In order to investigate the effect of FCPR03 on the expression of BDNF, LPS-treated mice were pretreated with 0.5 and 1 mg/kg FCPR03, and BDNF was detected by Western blot.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Phosphodiesterase 4 by FCPR03 Alleviates Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of p38 and JNK Signaling Pathways

Zou

Zhang

et al. 2018

IJMS

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Inflammatory responses induced by peripheral administration of lipopolysaccharide (LPS) triggers depressive-like behavioral syndrome in rodents. Inhibition of phosphodiesterase 4 (PDE4) produces a robust anti-inflammatory effect in inflammatory cells. Unfortunately, archetypal PDE4 inhibitors cause intolerable gastrointestinal side-effects, such as vomiting and nausea. N-isopropyl-3-(cyclopropylmethoxy)-4-difluoromethoxy benzamide (FCPR03) is a novel, selective PDE4 inhibitor with little, or no, emetic potency. Our previous studies show that FCPR03 is effective in attenuating neuroinflammation in mice treated with LPS. However, whether FCPR03 could exert antidepressant-like effect induced by LPS is largely unknown. In the present study, mice injected intraperitoneally (i.p.) with LPS was established as an in vivo animal model of depression. The antidepressant-like activities of FCPR03 were evaluated using a tail suspension test, forced swimming test, and sucrose preference test. We demonstrated that administration of FCPR03 (1 mg/kg) produced antidepressant-like effects in mice challenged by LPS, as evidenced by decreases in the duration of immobility in the forced swim and tail suspension tests, while no significant changes in locomotor activity were observed. FCPR03 also increased sucrose preference in mice treated with LPS. In addition, treatment with FCPR03 abolished the downregulation of brain-derived neurotrophic factor induced by LPS and decreased the level of corticosterone in plasma. Meanwhile, periphery immune challenge by LPS induced enhanced phosphorylation of p38-mitogen activated protein kinase (p38) and c-Jun N-terminal kinase (JNK) in both the cerebral cortex and hippocampus in mice. Interestingly, treatment with FCPR03 significantly blocked the role of LPS and reduced the levels of phosphorylated p38 and JNK. Collectively, these results indicate that FCPR03 shows antidepressant-like effects in mice challenged by LPS, and the p38/JNK signaling pathway is possibly involved in this process. Our findings suggest that FCPR03 is a potential compound for the prevention or treatment of depression.

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“…In our present study, we found that BDNF expression significantly increased after CPA in parallel with a decreased expression in ERK and no changes in CREB or pro‐BDNF expression in DG and BLA. Although it has been demonstrated a dual and directional regulatory mechanism between BDNF/ERK/CREB (for review, see Sawamoto et al), other factors could be implicated in the modulation of the BDNF pathway. It is known that BDNF undergoes both retrograde and anterograde transport, so BNDF could be transported from VTA to BLA or DG, without changes in pCREB and ERK in these areas.…”

Section: Discussionmentioning

confidence: 99%

Conditioned aversive memory associated with morphine withdrawal increases brain‐derived neurotrophic factor in dentate gyrus and basolateral amygdala

et al. 2019

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Morphine has been shown to increase the expression of brain‐derived neurotrophic factor (BDNF) in the brain. However, little is known about the effect of conditioned naloxone‐precipitated morphine withdrawal on BDNF and its precursor protein, proBDNF. We used the conditioned place aversion (CPA) paradigm to evaluate the role of corticotropin‐releasing factor (CRF)/CRF1 receptor signaling on the BDNF expression and corticosterone plasma levels after CPA expression and extinction. Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone‐associated compartment. The expression of BDNF and proBDNF in the dentate gyrus (DG) and basolateral amygdala (BLA) was measured in parallel with the corticosterone plasma levels with and without CRF1 receptor blockade. Mice subjected to conditioned naloxone‐induced morphine withdrawal showed an increased expression of BDNF (in DG and BLA) in parallel with an enhancement of corticosterone plasma levels. These results demonstrated that BDNF expression together with the increased activity of hypothalamic‐pituitary‐adrenocortical (HPA) axis are critical to the acquisition of aversive memory. However, we have observed a decrease in corticosterone plasma levels and BDNF expression after CPA extinction reaffirming the importance of BDNF in the maintenance of aversive memory. In addition, the pre‐treatment with the CRF1 receptor antagonist CP‐154 526 before naloxone conditioning session impaired morphine withdrawal‐induced aversive memory acquisition, the increased corticosterone plasma levels, and the expression of BDNF observed after CPA expression in the DG and BLA. Altogether, present results are suggesting a clear connection between HPA axis and BDNF in the formation and extinction of aversive memory.

show abstract

3,5,6,7,8,3′,4′-Heptamethoxyflavone Ameliorates Depressive-Like Behavior and Hippocampal Neurochemical Changes in Chronic Unpredictable Mild Stressed Mice by Regulating the Brain-Derived Neurotrophic Factor: Requirement for ERK Activation

Cited by 39 publications

References 45 publications

Antidepressant Flavonoids and Their Relationship with Oxidative Stress

Antidepressant Flavonoids and Their Relationship with Oxidative Stress

Inhibition of Phosphodiesterase 4 by FCPR03 Alleviates Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of p38 and JNK Signaling Pathways

Conditioned aversive memory associated with morphine withdrawal increases brain‐derived neurotrophic factor in dentate gyrus and basolateral amygdala

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