Coptisine from Rhizoma coptidis exerts an anti-cancer effect on hepatocellular carcinoma by up-regulating miR-122

Chai, Fangni; Ma, Wenxue; Zhang, Jian; Xu, Huiqin; Li, Yuanfeng; Q, Zhou; Li, Xuegang; Ye, Xiaoli

doi:10.1016/j.biopha.2018.04.052

Cited by 45 publications

(17 citation statements)

References 28 publications

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“…CR, the dried rhizome of Coptis chinensis Franch, mainly containing alkaloids such as berberine, coptisine, and palmatine, has been used in China for thousands of years to treat diarrhea. Moreover, recent researches have showed that CR has anti-bacterial [ 14 ], anti-cancer [ 15 ] activities, etc. Especially, berberine has been shown to possess remarkable effects on lowering blood glucose and promoting the secretion of insulin [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway

Cui

Qian

Jiang

et al. 2018

IJMS

183

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Aim Scutellariae Radix (SR) and Coptidis Rhizoma (CR) have often been combined to cure type 2 diabetes mellitus (T2DM) in the clinical practice for over thousands of years, but their compatibility mechanism is not clear. Mitogen-activated protein kinase (MAPK) signaling pathway has been suggested to play a critical role during the process of inflammation, insulin resistance, and T2DM. This study was designed to investigate their compatibility effects on T2DM rats and explore the underlying mechanisms by analyzing the metabolic profiling and MAPK/PI3K/Akt signaling pathway. Methods The compatibility effects of SR and CR were evaluated with T2DM rats induced by a high-fat diet (HFD) along with a low dose of streptozocin (STZ). Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to discover potential biomarkers. The levels of pro-inflammatory cytokines; biochemical indexes in serum, and the activities of key enzymes related to glycometabolism in liver were assessed by ELISA kits. qPCR was applied to examine mRNA levels of key targets in MAPK and insulin signaling pathways. Protein expressions of p65; p-p65; phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K); phosphorylated-PI3K (p-PI3K); protein kinase B (Akt); phosphorylated Akt (p-Akt) and glucose transporter 2 (Glut2) in liver were investigated by Western blot analysis. Results Remarkably, hyperglycaemia, dyslipidemia, inflammation, and insulin resistance in T2DM were ameliorated after oral administration of SR and CR, particularly their combined extracts. The effects of SR, CR, low dose of combined extracts (LSC) and high dose of combined extracts (HSC) on pro-inflammatory cytokine transcription in T2DM rats showed that the MAPK pathway might account for the phenomenon with down-regulation of MAPK (P38 mitogen-activated protein kinases (P38), extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK)) mRNA, and protein reduction in p-P65. While mRNA levels of key targets such as insulin receptor substrate 1 (IRS1), PI3K, Akt2, and Glut2 in the insulin signaling pathway were notably up-modulated, phosphorylations of PI3K, Akt, and expression of Glut2 were markedly enhanced. Moreover, the increased activities of phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), glucose 6-phosphatase (G6Pase), and glycogen phosphorylase (GP) were highly reduced and the decreased activities of glucokinase (GK), phosphofructokinase (PFK), pyruvate kinase (PK), and glycogen synthase (GS) in liver were notably increased after treatment. Further investigation indicated that the metabolic profiles of plasma and urine were clearly improved in T2DM rats. Fourteen potential biomarkers (nine in plasma and five in urine) were identified. After intervention, these biomarkers returned to normal level to some extent. Conclusion The results showed that SR, CR, and combined extract groups were normalized. The effects of combined extracts were more remarkable than single herb treatm...

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Section: Introductionmentioning

confidence: 99%

Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway

Cui

Qian

Jiang

et al. 2018

IJMS

183

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“…Rhizoma coptidis, which is called as ”Huang Lian” in China, is an important herbal medicine that contains alkaloids, such as berberine, coptisine, palmatine, jatrorrhizine [ 10 ]. As reported, Coptisine exhibited numerous pharmacological activities, such as antibacterial, anti-hyperlipidemic, anticachectic, and antitumor properties [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Coptisine Suppresses Mast Cell Degranulation and Ovalbumin-Induced Allergic Rhinitis

Wang

et al. 2018

Molecules

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Coptisine is one of the main components of isoquinoline alkaloids in the coptidis rhizome. The effect of coptisine on allergic rhinitis has not been investigated. In this study, we report the effects and mechanisms of coptisine using monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA)-stimulated rat basophilic leukemia cells (RBL-2H3 cells) in vitro and an ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. The results showed that coptisine markedly decreased the levels of β-hexosaminidase, histamine, interleukin (IL)-4, and tumor necrosis factor (TNF)-α. Coptisine also prevented morphological changes, such as restoring an elongated shape, inhibiting granule release on toluidine blue staining, and reorganizing inhibited filamentous actins (F-actin). Additionally, coptisine blocked the phosphorylation of phosphoinositide3-kinase (PI3K)/Akt (as known as protein kinase B(PKB)) in RBL-2H3 cell. Furthermore, the results showed that coptisine suppressed OVA-induced allergic rhinitis symptoms, such as nasal rubbing and OVA-specific IgE, and histamine, IL-4 and TNF-α levels in the serum of AR mice. These data suggested that coptisine should have inhibitory effects on the inflammatory responses of mast cells, and may be beneficial for the development of coptisine as a potential anti-allergic drug.

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“…Numerous studies have elucidated the mechanisms underlying the extinction of drug-associated memories (McNally, 2014). One key target of interests is AMPA receptors that play an important role in persistence of memory across time, and extinction of drug-associated memory (Watterson and Olive, 2013;Trent et al, 2017;Chai et al, 2018). Several manipulations, including GluR2 overexpression and NMDA receptor partial agonist D -cycloserine administration, effectively promote extinction of drug seeking A B C FIGURE 6 | The effect of berberine treatment and extinction training on the expression of BDNF, GluA1, and GluA2 in the NAc (A) The experimental timeline of the CPP training and tests, drug treatments, and tissues collection (B) Representative image of GluA1, GluA2, and BDNF expression detected by Western blot analysis (for original full image see supplementary files, Figure S2) (C) The expressions of BDNF, GluA1, and GluA2 (fold of control-no extinction group) in the NAc.…”

Section: Discussionmentioning

confidence: 99%

Berberine Facilitates Extinction of Drug-Associated Behavior and Inhibits Reinstatement of Drug Seeking

et al. 2020

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A high rate of relapse is a major clinical problem among drug-addicted individuals. Persistent traces of drug-associated reward memories contribute to intense craving and often trigger relapse. A number of interventions on drug-associated memories have shown significant benefits in relapse prevention. Among them are pre-or post-extinction pharmacological manipulations that facilitate the extinction of drug-associated behavior. Berberine, a bioactive isoquinoline alkaloid, has been recently reported to provide therapeutic benefits for a number of central nervous system (CNS) disorders, including morphine addiction. The present study aimed to investigate whether berberine could serve as a post-extinction pharmacological intervention agent to reduce risks of reinstatement of drug seeking. We found that an intragastric administration of berberine at doses of 25 and 50 mg/kg during the critical time window significantly facilitated the extinction of morphine-reward related behavior in free access and confined conditioned place preference (CPP) extinction paradigms, and subsequently, it prevented reinstatement and spontaneous recovery of morphine-induced CPP in mice. Intriguingly, the berberine treatment with or without extinction training altered expression of plasticity-related proteins such as brain-derived neurotrophic factor (BDNF), AMPA receptors (GluA1 and GluA2) in the nucleus accumbens (NAc). Moreover, the post-extinction berberine treatment significantly reduced reinstatement of cocaine-induced CPP and operant intravenous self-administration (IVSA) memories in rats. Altogether, our findings suggest that extinction training combined with the postextinction berberine treatment can facilitate extinction of drug-associated behavior making it an attractive therapeutic candidate in relapse prevention.

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Coptisine from Rhizoma coptidis exerts an anti-cancer effect on hepatocellular carcinoma by up-regulating miR-122

Cited by 45 publications

References 28 publications

Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway

Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway

Coptisine Suppresses Mast Cell Degranulation and Ovalbumin-Induced Allergic Rhinitis

Berberine Facilitates Extinction of Drug-Associated Behavior and Inhibits Reinstatement of Drug Seeking

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