Curcumin for attention-deficit–hyperactivity disorder: a systematic review and preliminary behavioral investigation

Macedo, Lélia Lilianna Borges de Sousa; Antunes, Flavia Tasmin Techera; Alvarenga, Willyane de Andrade; Batista, Mara Cristina Carvalho; Moura, Mayara Storel Beserra de; Farias, Mariane Nunes Lima; Caminski, Emanuelle Sistherenn; Dallegrave, Eliane; Grivicich, Ivana; Souza, Alessandra Hübner de

doi:10.1007/s00210-022-02236-0

Cited by 4 publications

(3 citation statements)

References 63 publications

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“…Curiously, one month of ABA treatment increased spontaneous activity in lesioned females, whereas in males had the opposite effect, preventing the lesion-induced hyperactivity. Our results in males are in accordance with a recent study with hypertensive rats (considered a spontaneous ADHD model with regards to certain symptoms) that showed that curcumin could rescue hyperactive status in males [61]. Thus, our result suggests a different effect of the dopaminergic lesion in both sexes and a different response to ABA treatment.…”

Section: Discussionsupporting

confidence: 92%

Targeting neuroinflammation with Abscisic Acid reduces pain sensitivity in females and hyperactivity in males of an ADHD mice model

Meseguer-Beltrán

Sánchez-Sarasúa

Landry

et al. 2022

Preprint

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Aims: Attention deficit/ hyperactivity disorder (ADHD) is a neurodevelopmental syndrome characterized by dopaminergic dysfunction. In this study, we aimed to demonstrate the link between dopaminergic deficit and neuroinflammation underlying ADHD symptoms. Subjects and Treatment: We used a validated ADHD mice model, that involves perinatal 6-OHDA lesion. Animals were treated with 20mg/L (drinking water) of Abscisic acid (ABA) for one month. We tested behaviour (learning and memory, anxiety, social interactions, and pain) in both females and male mice, in all eight groups (control and lesioned, with/without ABA). Postmortem, we analyzed microglia morphology and Ape1 expression in specific brain areas related to the descending pain inhibitory pathway. Results: In females, dopaminergic deficit increased pain sensitivity, but not hyperactivity, in contrast to males. This behaviour was associated with inflammatory microglia and lower Ape1 levels in the anterior cingulate cortex (ACC) and posterior insula cortex (IC). ABA treatment reduced inflammation and alleviated pain. In males, ABA reduced hyperactivity, but had no significant effect on inflammation. Conclusions: This is the first study proving a sex-dependent association between dopamine dysfunction and inflammation in specific brain areas, leading to different behavior outcomes in a mouse model of ADHD. These findings provide new clues for potential treatments.

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Section: Discussionsupporting

confidence: 92%

Targeting neuroinflammation with Abscisic Acid reduces pain sensitivity in females and hyperactivity in males of an ADHD mice model

Meseguer-Beltrán

Sánchez-Sarasúa

Landry

et al. 2022

Preprint

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“…One month of ABA treatment reduced spontaneous locomotor activity in males, suggesting a potential beneficial effect in managing hyperactivity. This result aligns with the effect that curcumin, a well-known anti-inflammatory molecule, exerts an effect on a hypertensive rat model (considered a spontaneous ADHD model), also reducing hyperactivity in males [61]. However, we observed that ABA increased spontaneous activity in the lesioned females, suggesting an interaction between the lesion and ABA.…”

Section: Discussionsupporting

confidence: 89%

Targeting Neuroinflammation with Abscisic Acid Reduces Pain Sensitivity in Females and Hyperactivity in Males of an ADHD Mice Model

Meseguer-Beltrán

Sánchez-Sarasúa

Landry

et al. 2023

Cells

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Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome characterized by dopaminergic dysfunction. In this study, we aimed to demonstrate that there is a link between dopaminergic deficit and neuroinflammation that underlies ADHD symptoms. We used a validated ADHD mice model involving perinatal 6-OHDA lesions. The animals received abscisic acid (ABA), an anti-inflammatory phytohormone, at a concentration of 20 mg/L (drinking water) for one month. We tested a battery of behavior tests, learning and memory, anxiety, social interactions, and pain thresholds in female and male mice (control and lesioned, with or without ABA treatment). Postmortem, we analyzed microglia morphology and Ape1 expression in specific brain areas related to the descending pain inhibitory pathway. In females, the dopaminergic deficit increased pain sensitivity but not hyperactivity. In contrast, males displayed hyperactivity but showed no increased pain sensitivity. In females, pain sensitivity was associated with inflammatory microglia and lower Ape1 levels in the anterior cingulate cortex (ACC) and posterior insula cortex (IC). In addition, ABA treatment alleviated pain sensitivity concomitant with reduced inflammation and normalized APE1. In males, ABA reduced hyperactivity but had no significant effect on inflammation in these areas. This is the first study proving a sex-dependent association between dopamine dysfunction and inflammation in specific brain areas, hence leading to different behavioral outcomes in a mouse model of ADHD. These findings provide new clues for potential treatments for ADHD.

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“…Fiji Is Just ImageJ (Fiji) software was used to analyze the movement distance, speed, and time spent in the central area of the rats. The activity of each rat was observed for 5 min (Song et al, 2021;de Sousa Macedo et al, 2022). After the test, 75% alcohol was used to remove the odor.…”

Section: Open Field Test (Oft)mentioning

confidence: 99%

Network pharmacology, molecular docking, and experimental validation to explore the potential mechanism of Long Mu Qing Xin mixture for the treatment of attention deficit hyperactivity disorder

Xiao

et al. 2023

Front. Pharmacol.

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Background: Long Mu Qing Xin Mixture (LMQXM) has shown potentially positive effects in alleviating attention deficit hyperactivity disorder (ADHD); however, the action mechanism is still not fully understood. This study aimed to predict the potential mechanism of LMQXM for ADHD using network pharmacology and molecular docking, which were then validated using animal experiments.Methods: Network pharmacology and molecular docking techniques were used to predict the core targets and potential pathways of LMQXMQ for ADHD, and KEGG pathway enrichment analysis revealed the potential significance of dopamine (DA) and cyclic adenosine monophosphate (cAMP) signaling pathways. To verify the hypothesis, we conducted an animal experiment. In the animal experiment, the young spontaneously hypertensive rats (SHRs) were randomly divided into the model group (SHR), the methylphenidate hydrochloride group (MPH, 4.22 mg/kg), and 3 LMQXM groups (low-dose (LD) group, 5.28 ml/kg; medium-dose (MD) group, 10.56 ml/kg; and high-dose (HD) group, 21.12 ml/kg), and administered by gavage for 4 weeks; the WKY rats were set as the control group. The open field test and Morris water maze test were used to evaluate the behavioral performance of rats, high performance liquid chromatography mass spectrometry (LC-MS) was used to analyze DA levels in the prefrontal cortex (PFC) and striatum of rats, ELISA was used to detect cAMP concentrations in the PFC and striatum, and immunohistochemistry and qPCR were used to analyze positive cell expression and mRNA expression for indicators related to DA and cAMP pathways.Results: The results showed that beta-sitosterol, stigmasterol, rhynchophylline, baicalein, and formononetin might be key components of LMQXM for ADHD and that these components bind well to the core targets, DA receptors (DRD1 and DRD2). Furthermore, LMQXM might act through the DA and cAMP signaling pathways. In the animal experiment, we found that MPH and LMQXM-MD controlled hyperactivity and improved learning and memory in SHRs, while LMQXM-HD only controlled hyperactivity in SHRs; meanwhile, MPH and LMQXM-MD upregulated DA and cAMP levels, mean optical density (MOD) of cAMP, and MOD and mRNA expression of DRD1 and PKA in the prefrontal cortex (PFC) and striatum of SHRs, while LMQXM-LD and LMQXM-HD upregulated DA and cAMP levels in the striatum, MOD of cAMP in the PFC, and mRNA expression of PKA in the PFC. However, we did not find a significant regulatory effect of LMQXM on DRD2.Conclusion: To sum up, this study demonstrated that LMQXM may increase DA levels mainly by activating the cAMP/PKA signaling pathway through DRD1, thereby controlling the behavioral disorders of SHRs, which is most effective at moderate doses, and this may be a key mechanism for LMQXM in the treatment of ADHD.

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Curcumin for attention-deficit–hyperactivity disorder: a systematic review and preliminary behavioral investigation

Cited by 4 publications

References 63 publications

Targeting neuroinflammation with Abscisic Acid reduces pain sensitivity in females and hyperactivity in males of an ADHD mice model

Targeting neuroinflammation with Abscisic Acid reduces pain sensitivity in females and hyperactivity in males of an ADHD mice model

Targeting Neuroinflammation with Abscisic Acid Reduces Pain Sensitivity in Females and Hyperactivity in Males of an ADHD Mice Model

Network pharmacology, molecular docking, and experimental validation to explore the potential mechanism of Long Mu Qing Xin mixture for the treatment of attention deficit hyperactivity disorder

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