Anti-Depressant-Like Effect of Sinomenine on Chronic Unpredictable Mild Stress-Induced Depression in a Mouse Model

Liu, Shengbing; Xu, Shuiling; Wang, Zhijian; Guo, Yanjun; Pan, Weiwei; Shen, Zhong‐Fei

doi:10.12659/msm.908422

Cited by 66 publications

(31 citation statements)

References 35 publications

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“…As previously described [25], mice were separately suspended in a cage (25 cm × 25 cm × 30 cm) by their tails 15 cm above the cage bottom with adhesive tape on day 0, day 21, and day 28. The total duration of the immobile time measured over the last 4 min of the 6-min test period was the dependent variable.…”

Section: Methodsmentioning

confidence: 99%

Chaihu-Shugan-San Reinforces CYP3A4 Expression via Pregnane X Receptor in Depressive Treatment of Liver-Qi Stagnation Syndrome

Fan

Zhang

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Backgrounds. Chaihu-Shugan-San (CSS) is a classic traditional Chinese herbal prescription for treating depression. However, the underlying mechanism of the Chinese syndrome-specific efficacy of CSS is poorly understood. Aim of the Study. From traditional Chinese medicine and pharmacogenetics perspectives, the present study aimed to investigate the antidepressant effects of CSS on a mouse model of Liver-Qi Stagnation (LQS) syndrome and its underlying mechanisms. Methods and Materials. We used two main mouse models of depressive syndromes in the study, including LQS and liver stagnation and spleen deficiency (LSSD) syndrome. Tail suspension and forced swimming tests were used to evaluate the effects of CSS on animal behaviour. The expression level of the CYP450 enzyme from liver microsomes was analysed by western blot (WB) analysis and quantitative real-time polymerase chain reaction (qRT-PCR). More specifically, we analysed the key compounds of CSS that are responsible for CYP450 regulation via bioinformatics. Ultimately, luciferase assays were employed to confirm the prediction in vitro. Results. CSS remarkably reduced the immobile time in LQS rather than in LSSD mice. Although CSS significantly upregulated CYP2C9 in mice with both syndromes, activated translation of CYP3A4 induced by CSS was only observed in the LQS group. Bioinformatics analysis revealed that the unique regulation of CYP3A4 was responsible for the effects of glycyrrhetinic acid (GA) from CSS. Further luciferase assays confirmed the enhancement of CYP3A4 expression via the pregnane X receptor (PXR) pathway in vitro. Conclusions. CSS specifically upregulates the translation of CYP3A4 via the PXR pathway in depressed LQS mice. GA, a bioactive compound that originates from CSS, contributes to this activation. This work provides novel insight into Chinese syndrome-based therapy for depression.

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Section: Methodsmentioning

confidence: 99%

Chaihu-Shugan-San Reinforces CYP3A4 Expression via Pregnane X Receptor in Depressive Treatment of Liver-Qi Stagnation Syndrome

Fan

Zhang

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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“…In addition, high-efficacy 5-HT 1A receptor agonists such as F13640 can produce intra- and postoperative analgesic effect 35 . Because sinomenine can attenuate CUMS-induced NE and 5-HT reduction in the mouse brain 36 . So, a dose of 1 mg/kg 5-HT 1A receptor antagonist WAY100635, which sufficiently blocks 5-HT 1A receptors 19 , 37 , was used to investigate whether 5-HT 1A receptor mediates N -demethylsinomenine-induced anti-allodynia.…”

Section: Discussionmentioning

confidence: 97%

N-Demethylsinomenine, an active metabolite of sinomenine, attenuates chronic neuropathic and inflammatory pain in mice

Zhou

Qiu

et al. 2021

Sci Rep

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Chronic pain is a significant public health problem that afflicts nearly 30% of the global population, but current pharmacotherapies are insufficient. Previous report indicated that N-demethylsinomenine, an active metabolite of sinomenine, is efficacious against postoperative pain. The present study investigated whether N-demethylsinomenine is effective for chronic painful conditions or whether repeated treatment alters its effect. Both chronic constriction injury (CCI) surgery and complete Freund’s adjuvant (CFA) intraplantar injection induced significant and reliable mechanical allodynia at least for 7 days. Acute treatment with N-demethylsinomenine (10–40 mg/kg, i.p.) dose-dependently attenuated the mechanical allodynia both in CCI-induced neuropathic pain and CFA-induced inflammatory pain in mice. The potency of N-demethylsinomenine for reducing CFA-induced mechanical allodynia was slightly higher than sinomenine. During the period of repeated treatment, N-demethylsinomenine maintained its anti-allodynic effect against both neuropathic and inflammatory pain without producing carry-over effect. Pretreatment with bicuculline, a selective γ-aminobutyric acid type A (GABAA) receptor antagonist, almost completely blocked the anti-allodynia of N-demethylsinomenine (40 mg/kg) both in CCI and CFA-treated mice. Our findings indicated that N-demethylsinomenine exhibits GABAA receptor-mediated anti-allodynic effects in mouse models of neuropathic and inflammatory pain, suggesting it may be a useful novel pharmacotherapy for the control of chronic pain.

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“…Regarding the effect of surgery on hippocampal NA, Ying Xu et al reported that rats with depression caused by olfactory bulbectomy showed a decrease of hippocampal NA two weeks after the surgery [34]. Liu et al demonstrated that chronic unpredictable mild stress for 6 weeks caused depressive behaviors accompanied by a decrease of hippocampal NA in mice [35]. According to these findings, we considered that the surgical stress in the T2DM model mice induced the decrease of hippocampal NA and that it might be associated with suppression of behavior in the T2DM model mice after surgery.…”

Section: Discussionmentioning

confidence: 99%

Suppression of behavioral activity and hippocampal noradrenaline caused by surgical stress in type 2 diabetes model mice

Nishimura

Nomura

Egi

et al. 2020

Preprint

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Background: There has been much discussion recently about the occurrence of neuropsychological complications during the perioperative period. Diabetes is known to be one of the metabolic risk factors. Although the number of patients with diabetes mellitus (DM) has been increasing, the pathophysiology of postoperative neuropsychological dysfunction in DM patients is still unclear. Recently, a deficiency of neurotransmitters, such as monoamines, was reported to be associated with mental disorders. Therefore, we investigated the effects of surgical stress on behavioral activity and hippocampal noradrenaline (NA) level in type 2 diabetes mellitus model (T2DM) mice.Methods: Eighty-four 6-week-old male C57BL/6J mice were divided into four groups (non-diabetes, non-diabetes with surgery, T2DM, and T2DM with surgery groups). T2DM mice were established by feeding a high-fat diet (HFD) for 8 weeks. At 14 weeks of age, fifteen mice in each group underwent a series of behavioral tests including an open field (OF) test, a novel object recognition (NOR) test and a light-dark (LD) test. In the surgery groups, open abdominal surgery with manipulation of the intestine was performed 24 hours before the behavioral tests as a surgical stress. Hippocampal noradrenaline (NA) concentration was examined in six mice in each group by high-performance liquid chromatography. The data were analyzed by the Mann-Whitney U test, and p values less than 0.05 were considered significant.Results: The T2DM group showed significantly increased explorative activity in the NOR test (P = 0.0016) and significantly increased frequency of transition in the LD test (P = 0.043) compared with those in the non-diabetic group before surgery. In T2DM mice, surgical stress resulted in decreased total distance in the OF test, decreased explorative activity in the NOR test, and decreased frequency of transition in the LD test (OF: P = 0.015, NOR: P = 0.009, LD: P = 0.007) and decreased hippocampal NA (P = 0.015), but such differences were not observed in the non-diabetic mice.Conclusions: Mice with T2DM induced by feeding an HFD showed increased behavioral activities, and surgical stress in T2DM mice caused postoperative hypoactivity and reduction of the hippocampal NA level.

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Anti-Depressant-Like Effect of Sinomenine on Chronic Unpredictable Mild Stress-Induced Depression in a Mouse Model

Cited by 66 publications

References 35 publications

Chaihu-Shugan-San Reinforces CYP3A4 Expression via Pregnane X Receptor in Depressive Treatment of Liver-Qi Stagnation Syndrome

Chaihu-Shugan-San Reinforces CYP3A4 Expression via Pregnane X Receptor in Depressive Treatment of Liver-Qi Stagnation Syndrome

N-Demethylsinomenine, an active metabolite of sinomenine, attenuates chronic neuropathic and inflammatory pain in mice

Suppression of behavioral activity and hippocampal noradrenaline caused by surgical stress in type 2 diabetes model mice

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