Suppression of Vascular Endothelial Growth Factor via Inactivation of Eukaryotic Elongation Factor 2 by Alkaloids in <i>Coptidis rhizome</i> in Hepatocellular Carcinoma

Tan, Hor Yue; Wang, Ning; Tsao, Sai‐Wah; Zhang, Zhangjin; Feng, Yibin

doi:10.1177/1534735413513635

Cited by 35 publications

(25 citation statements)

References 31 publications

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“…Rhizoma coptidis , commonly known as Huang Lian in China, has been one of the most important medicinal plants used for the treatment of various diseases in traditional Chinese medicine for more than 2000 years. In recent years, numerous scientific studies have demonstrated that Rhizoma coptidis and its main active constituents display a variety of activities including anti‐bacterial, anti‐cancer, anti‐hyperglycemic, anti‐hyperlipidemic, anti‐diabetic, anti‐obesity, anti‐inflammatory, radio‐protective and hepato‐protective effects . Moreover, Rhizoma coptidis and its isolated alkaloids have been reported to have cardio‐protective and neuro‐protective properties.…”

Section: Introductionmentioning

confidence: 99%

Metabolic profile of Rhizoma coptidis in human plasma determined using ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry

Zhang

Wang

Han

et al. 2017

Rapid Comm Mass Spectrometry

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Rationale: Rhizoma coptidis extract and its alkaloids show various pharmacological activities, but its metabolic profile in human plasma has not been thoroughly investigated. In the present research, the metabolism of Rhizoma coptidis at a clinical dose (5 g/60 kg/day) was systematically analyzed to determine its biotransformation processes in human plasma.Methods: In this research, the metabolites of Rhizoma coptidis in human plasma after oral administration of Rhizoma coptidis extract at a clinical dose were investigated using ultrahigh-performance liquid chromatography (UHPLC) coupled with high-resolution LTQ-Orbitrap mass spectrometry. The structural elucidation of the constituents was confirmed by comparing their retention times (t R ) and MS n fragments with those of standards and literature reports.Results: In total, two prototypes and twelve metabolites were detected in human plasma. The two prototypes were confidently identified using reference standards. Of the compounds detected, M7 (berberrubinen-9-O-glucuronide) was the most abundant based on its peak area, which indicates that this compound might be a pharmacokinetic marker for Rhizoma coptidis alkaloids in humans. Based on the metabolites detected in human plasma, a possible metabolic pathway for Rhizoma coptidis in vivo was proposed. Conclusions:The results indicated that the alkaloids in Rhizoma coptidis were extensively biotransformed in vivo mainly via conjugation with glucuronic acid (GluA) or sulfuric acid (SulA) to form phase II metabolites, and the GluA metabolites are likely the dominant form in human plasma. To the best of our knowledge, this is the first in vivo evaluation of the metabolic profile of the whole Rhizoma coptidis extract in human plasma, which is essential for determining the chemicals responsible for the pharmacological activities of Rhizoma coptidis in vivo. Moreover, it would be beneficial for us to further systematically study the pharmacokinetic behavior of Rhizoma coptidis in humans.

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Section: Introductionmentioning

confidence: 99%

Metabolic profile of Rhizoma coptidis in human plasma determined using ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry

Zhang

Wang

Han

et al. 2017

Rapid Comm Mass Spectrometry

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“…1A), similar to other cancers after treatment of 100 µg/ml CR (17)(18)(19). In addition, we assessed the cell viability in other melanoma cell lines, M14 (BRAF V600E), Malme3M (BRAF V600E), MeWo (no mutation in BRAF and NRAS), and SK-MEL-2 (NRAS Q61R), with a different genetic background (Fig.…”

Section: Cr Inhibits the Cell Viability In Some Melanoma Cell Linesmentioning

confidence: 99%

Coptidis Rhizoma induces intrinsic apoptosis through BAX and BAK activation in human melanoma

Yokoyama

Hayakawa

et al. 2017

Oncology Reports

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Abstract. Malignant melanoma has exhibited a rising incidence in recent years worldwide. Although various molecular targeted drugs are being researched and developed for melanoma patients, their efficacy appears to be unsatisfactory. Over the past few years, several reports have demonstrated that Coptidis Rhizoma water extracts (CR) or its major active chemical component, berberine, has anticancer activities in various types of cancer, including melanoma. However, their underlying mechanisms have not been well understood. In the present study, we determined that CR suppressed melanoma cell viability, which was mainly mediated through apoptosis. In addition, the expression levels of anti-apoptotic proteins, BCL2A1, MCL1 and BCL-w, were strongly suppressed by CR treatment. Furthermore, multi-domain pro-apoptotic proteins BAX and BAK were activated by CR treatment and were also required for the CR-induced apoptosis. Collectively, CR or some formulations containing CR, may be effective safe treatment strategies for human melanoma.

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“…Three batches of HLJDD were analyzed and the common chemical profile of the decoction was generated by recognizing relevant peaks on the chromatogram. Analysis of any heavy metals and organic pesticides contamination were conducted with methods described in our previous study (Tan et al, 2013).…”

Section: Chemical Analysismentioning

confidence: 99%

Inhibition of eukaryotic elongation factor-2 confers to tumor suppression by a herbal formulation Huanglian-Jiedu decoction in human hepatocellular carcinoma

Wang

Feng

Tan

et al. 2015

Journal of Ethnopharmacology

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Suppression of Vascular Endothelial Growth Factor via Inactivation of Eukaryotic Elongation Factor 2 by Alkaloids in Coptidis rhizome in Hepatocellular Carcinoma

Abstract: Our study postulates the antiangiogenic effect of CRAE on hepatocellular carcinoma via an eEF2-driven pathway.

Cited by 35 publications

References 31 publications

Metabolic profile of Rhizoma coptidis in human plasma determined using ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry

Metabolic profile of Rhizoma coptidis in human plasma determined using ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry

Coptidis Rhizoma induces intrinsic apoptosis through BAX and BAK activation in human melanoma

Inhibition of eukaryotic elongation factor-2 confers to tumor suppression by a herbal formulation Huanglian-Jiedu decoction in human hepatocellular carcinoma

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