Protective and restorative effects of the traditional Chinese medicine Jitai tablet against methamphetamine-induced dopaminergic neurotoxicity

Xu, Shasha; Tu, Shaoang; Gao, Jinlong; Liu, Jia; Guo, Zhirui; Zhang, Jinming; Liu, Xingdang; Liang, Jing; Huang, Yiyun; Han, Mei

doi:10.1186/s12906-018-2094-z

Cited by 6 publications

(4 citation statements)

References 50 publications

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“…As expected, GQD treatment can significantly attenuate anxiety level in Meth-withdrawn mice. Although a few reports were concerning the roles of TCM (mostly monomer) in antagonizing Meth associated neuro-damages [ 38 – 42 ], this study, to our knowledge, firstly reported that GQD mitigated the Meth withdrawal neurobehavioral abnormalities. Recently, by improving the compositions of gut microbial, GQD shows a desirable therapeutic effect on diseases like diabetes, cancers, ulcerative colitis, obesity and hypertension [ 18 – 22 ].…”

Section: Discussionmentioning

confidence: 62%

Gegen-Qinlian decoction alleviates anxiety-like behaviors in methamphetamine-withdrawn mice by regulating Akkermansia and metabolism in the colon

et al. 2023

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Background Anxiety is a prominent withdrawal symptom of methamphetamine (Meth) addiction. Recently, the gut microbiota has been regarded as a promising target for modulating anxiety. Gegen-Qinlian decoction (GQD) is a classical Traditional Chinese Medicine applied in interventions of various gut disorders by balancing the gut microbiome. We aim to investigate whether GQD could alleviate Meth withdrawal anxiety through balancing gut microbiota and gut microenvironment. Methods Meth withdrawal anxiety models were established in mice. GQD were intragastric administrated into Meth-withdrawn mice and controls. Gut permeability and inflammatory status were examined in mice. Germ-free (GF) and antibiotics-treated (Abx) mice were used to evaluate the role of gut bacteria in withdrawal anxiety. Gut microbiota was profiled with 16s rRNA sequencing in feces. Metabolomics in colon tissue and in Akkermansia culture medium were performed. Results Meth withdrawal enhanced anxiety-like behaviors in wild-type mice, and altered gut permeability, and inflammatory status, while GQD treatment during the withdrawal period efficiently alleviated anxiety-like behaviors and improved gut microenvironment. Next, we found Germ-free (GF) and antibiotics-treated (Abx) mice did not develop anxiety-like behaviors by Meth withdrawal, indicating the essential role of gut bacteria in Meth withdrawal induced anxiety. Then, it was observed that gut microbiota was greatly affected in Meth-withdrawn mice, especially the reduction in Akkermansia. GQD can rescue the gut microbiota and reverse Akkermansia abundance in Meth-withdrawn mice. Meanwhile, GQD can also restore the Meth-impaired Akkermansia growth in vitro. Further, GQD restored several common metabolite levels both in colon in vivo and in Akkermansia in vitro. Conclusions We revealed a novel effect of GQD on Meth withdrawal anxiety and identified its pharmacological target axis as “Akkermansia-Akkermansia metabolites-gut metabolites-gut microenvironment”. Our findings indicated that targeting gut bacteria with TCM, such as GQD, might be a promising therapeutic strategy for addiction and related withdrawal symptoms.

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Section: Discussionmentioning

confidence: 62%

Gegen-Qinlian decoction alleviates anxiety-like behaviors in methamphetamine-withdrawn mice by regulating Akkermansia and metabolism in the colon

et al. 2023

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“…Recently, a Chinese herbal prescription was reported to upregulates the striatal DAT and attenuates stereotyped behavior of Tourette syndrome in rats [50]. In addition, another traditional Chinese medicine was noticed to exert the protective and restorative effects against methamphetamine-induced dopaminergic neurotoxicity: it attenuates the stereotyped responses and restores DAT expression to the normal level [51]. Together, it is a reliable belief that DAT inhibition, as well as the resulting DA accumulation, is a key mechanism underlying TD development.…”

Section: Discussionmentioning

confidence: 99%

Striatal Syntaixin 1A Plays a Protective Role Against Iminodipropionitrile Induced Tic Disorder Through Interaction with Dopamine Transporter

Liu¹,

Wang

2022

Preprint

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An important mechanism of Tic disorder (TD) is dysfunction in the dopamine (DA) system. Our pilot observation found the expression of Syntaxin 1A (STX1A), a presynaptic SNARE complex, changed in the striatum of TD animals. The present study aimed to clarify the biological role of striatal STX1A in the pathological state of TD and the specific mechanism of its regulation of the dopaminergic system. The TD rat model was established using iminodipropionitrile (IDPN). Adenovirus was used to modulate the expression of STX1A and dopamine transporter (DAT) in vivo and vitro. Primary culture of striatal dopaminergic neurons was performed for in-vitro observation of the DA reuptake, CO-IP analysis of the interaction between STX1A and DAT. First, using immunofluorescence staining, Western blotting, and qPCR, we found that the IDPN induced TD model had reduced striatal STX1A expression. In vitro, the DA content in the supernatant was significantly lower in the STX1A overexpressed group, and the intracellular DA content was significantly higher. Overexpression of STX1A in vivo partially counteracts the IDPN-induced TD-like behaviors, including bite time and head shaking time. Meanwhile, in-vivo knockdown of STX1A can aggravates TD-like behaviors. Further, DAT was overexpressed in vivo, and the TD-like behavior was alleviated. Interestingly, overexpression of DAT in the striatum resulted in increased levels of STX1A. In order to clarify the interaction between DAT and STX1A, the CO-IP analysis was conducted based on the protein of purified striatal dopaminergic neurons. Compared to the IgG control, the blots of DAT and STX1A showed significant binding of each other. Striatal STX1A expression is decreased in TD development, and STX1A plays an anti-TD role possibly through interaction with DAT, which maintains the DA reuptake. The exorbitant DA signal caused by STX1A inhibition drives the pathological stereotyped behavior.

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“…23 Jitai tablets were purchased as a positive control drug of Traditional Chinese Medicine from Wuhan Ezhong Pharmaceutical Co., Ltd. (Hubei, China). [24][25][26] OA, clonidine hydrochloride tablets, and Jitai tablets were all prepared as warm water suspensions. Morphine hydrochloride solution for injection was obtained from Shenyang No.1 Pharmaceutical Co., Ltd. of Northeast Pharmaceutical Group (Liaoning, China).…”

Section: Materials and Methods Chemicalsmentioning

confidence: 99%

Oleanolic Acid Attenuates Morphine Withdrawal Symptoms in Rodents: Association with Regulation of Dopamine Function

Shi¹,

Pan

Wang

et al. 2021

DDDT

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Introduction: Oleanolic acid (OA) has been shown to be useful for the treatment of mental disorders. Methods: In this study, we investigated the effects of OA in animal models of spontaneous withdrawal and naloxone-precipitated withdrawal and evaluated the effects of OA on the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference (CPP). Results: OA significantly improved symptoms of withdrawal, and significantly reduced the acquisition and reinstatement of morphine-induced conditioned place preference. Moreover, OA significantly reduced the serum content of 5-hydroxy tryptamine (5-HT) and dopamine (DA) in a dose-dependent manner, and reduced norepinephrine (NE) and 5-HT content in the frontal cortex (PFC), while significantly increasing endorphin content in rats. OA also significantly reduced serum DA content in mice. Conclusion:These results indicate that OA can improve the withdrawal symptoms of rats and mice by regulating the DA system and suggest that OA may be useful in treatment of morphine addiction.

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Protective and restorative effects of the traditional Chinese medicine Jitai tablet against methamphetamine-induced dopaminergic neurotoxicity

Abstract: Our results indicated that JTT protects against METH-induced neurotoxicity and restores the dopaminergic function, and thus might be a potential treatment for the dopaminergic deficits associated with METH abuse.

Cited by 6 publications

References 50 publications

Gegen-Qinlian decoction alleviates anxiety-like behaviors in methamphetamine-withdrawn mice by regulating Akkermansia and metabolism in the colon

Gegen-Qinlian decoction alleviates anxiety-like behaviors in methamphetamine-withdrawn mice by regulating Akkermansia and metabolism in the colon

Striatal Syntaixin 1A Plays a Protective Role Against Iminodipropionitrile Induced Tic Disorder Through Interaction with Dopamine Transporter

Oleanolic Acid Attenuates Morphine Withdrawal Symptoms in Rodents: Association with Regulation of Dopamine Function

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