Anticancer Activity of Atractylodes lancea (Thunb.) DC in a Hamster Model and Application of PET-CT for Early Detection and Monitoring Progression of Cholangiocarcinoma

Plengsuriyakarn, Tullayakorn; Matsuda, Naoki; Karbwang, Juntra; Viyanant, Vithoon; Hirayama, Kenji; Na‐Bangchang, Kesara

doi:10.7314/apjcp.2015.16.15.6279

Cited by 20 publications

(21 citation statements)

References 29 publications

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“…Comparable anti-CCA activity and inhibitory activity on lung metastasis were also observed with BE. 19 In the hamster model, the promising anti-CCA activity of AL was observed at all dose levels, particularly at the highest oral dose level of 5,000 mg/kg body weight for 30 days. The median survival time was significantly prolonged (about two times) in mice treated with the extract at all dose levels compared with 5-FU treated and untreated control groups.…”

Section: Discussionmentioning

confidence: 88%

“…The median survival time was significantly prolonged (about two times) in mice treated with the extract at all dose levels compared with 5-FU treated and untreated control groups. 19 Altogether, results suggest that the three major compounds in the AL rhizomes play an important role in the anti-CCA activity of AL. The study supports synergistic interaction of the active ingredients observed in all animal models.…”

Section: Discussionmentioning

confidence: 92%

“… 16 – 18 It is noted however that, with the relatively low amounts of all the three constituents in the AL extract, its anti-CCA activity observed in the in vivo CCA-xenografted mouse and O. viverrini /dimethylnitrosamine-induced CCA hamster models was shown to be higher than the isolated compound BE alone. 17 – 19 Significant inhibitory effects of AL extract on CCA tumor growth (2% of untreated control) were observed at the dose levels of 1,000, 3,000 and 5,000 mg/kg body weight, while the inhibitory effect of only 70% was found in the 5-FU treated mice. 17 The survival time of mice was about 3–4 times more prolonged following all dose levels of AL extract compared with 5-FU and untreated control.…”

Section: Discussionmentioning

confidence: 99%

“…(AL) and its isolated compounds (β-eudesmol [BE], atractylodin [AT], atractylon, hinesol [HS], etc). 15 – 19 The interest of our research group has been focusing on research and development of AL as a potential chemotherapeutic for CCA. AL is the therapeutic plant growing in tropical and subtropical zones of Asia such as People’s Republic of China, Japan, and Thailand.…”

Section: Introductionmentioning

confidence: 99%

“…Results from a series of our study confirm anti-CCA potential and safety profiles of both the crude ethanolic extract and the purified compound BE both in vitro and in animal models. 16 – 19 The present study aimed to investigate the cytotoxic interactions on human CCA between the three major isolated compounds from the AL rhizome, ie, BE, AT, and HS.…”

Section: Introductionmentioning

confidence: 99%

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Bioactive constituents isolated from <em>Atractylodes lancea</em> (Thunb.) DC. rhizome exhibit synergistic effect against cholangiocarcinoma cell

Martviset

Chai่jaroenkul

Muhamad

et al. 2018

JEP

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BackgroundCholangiocarcinoma (CCA) is the primary type of bile duct cancer with high morbidity and mortality, particularly in patients with advanced-stage disease. Treatment of CCA remains unsatisfactory due to the lack of sensitive and specific diagnostic tool for early detection as well as effective chemotherapeutics.PurposeTo investigate cytotoxic interactions between the three major constituents of the rhizomes of Atractylodes lancea (Thunb.) DC., ie, β-eudesmol (BE), atractylodin (AT), and hinesol (HS), against CCA cell line.MethodsCytotoxic activities against the human CCA cells CL-6 of the dual (BE:AT, BE:HS, and AT:HS) and triple (BE:AT:HS) combinations were evaluated using MTT assay. The cytotoxic interaction of each dual combination was assessed at five concentration ratios (10:0, 7:3, 5:5, 3:7, and 0:10) using isobologram analysis. For triple combination, the concentration ratio used in the experiment was 1:1.5:2.5 (BE:AT:HS) and analysis of the interaction was performed using polygonogram analysis at the concentrations that inhibit cell growth by 50% and 90%, respectively.ResultsThe BE:AT combination produced the additive effect with sum fractional inhibitory concentration of 0.967±0.02 (mean ± SD). The BE:HS and AT:HS combinations produced a synergistic effect with sum fractional inhibitory concentrations of 0.685±0.08 and 0.767±0.09, respectively. The mixture of the three compounds produced synergistic interaction with combination index values of 0.519±0.10 and 0.65±0.17 (mean ± SD) at the concentrations that inhibit cell growth at the 50% and 90% leveled, respectively.ConclusionResults obtained would guide further development of Atractylodes lancea (Thunb.) DC. as potential anti-CCA chemotherapeutics concerning the appropriate pharmaceutical dosage form.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bioactive constituents isolated from <em>Atractylodes lancea</em> (Thunb.) DC. rhizome exhibit synergistic effect against cholangiocarcinoma cell

Martviset

Chai่jaroenkul

Muhamad

et al. 2018

JEP

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The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β‐eudesmol in human liver: Reaction phenotyping and enzyme kinetics

Muhamad,

Na‐Bangchang

2023

Pharmacology Res & Perspec

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Abstractβ‐eudesmol is a major bioactive component of Atractylodes lancea (AL). AL has been developed as the capsule formulation of standardized AL extract for treating cholangiocarcinoma (CCA). However, the complex constituents of herbal products increase the risk of adverse drug interactions. β‐eudesmol has demonstrated inhibitory effects on rCYP2C19 and rCYP3A4 in the previous research. This study aimed to identify the cytochrome P450 (CYP) isoforms responsible for the metabolism of β‐eudesmol and determine the enzyme kinetic parameters and the metabolic stability of β‐eudesmol metabolism in the microsomal system. Reaction phenotyping using human recombinant CYPs (rCYPs) and selective chemical inhibitors of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was performed, and enzyme kinetics and metabolic stability were investigated using human liver microsome (HLM). The results suggest that CYP2C19 and CYP3A4 play significant roles in β‐eudesmol metabolism. The disappearance half‐life (t1/2) and intrinsic clearance (CLint) of β‐eudesmol were 17.09 min and 0.20 mL/min·mg protein, respectively. Enzyme kinetic analysis revealed the Michaelis–Menten constant (Km) and maximum velocity (Vmax) of 16.76 μM and 3.35 nmol/min·mg protein, respectively. As a component of AL, β‐eudesmol, as a substrate and inhibitor of CYP2C19 and CYP3A4, has a high potential for drug–drug interactions when AL is co‐administered with other herbs or conventional medicines.

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Atractylodes lancea (Thunb.) DC.: Ethnobotany, Phytochemistry, Pharmacological Attributes, and Safety Profile

Sanyal¹,

Paul²,

Das³

et al. 2022

Medicinal Plants of the Asteraceae Family

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Anticancer Activity of Atractylodes lancea (Thunb.) DC in a Hamster Model and Application of PET-CT for Early Detection and Monitoring Progression of Cholangiocarcinoma

Abstract: Opisthorchis viverrini (OV)-induced cholangiocarcinoma (CCA) is an important cancer in the Great

Cited by 20 publications

References 29 publications

Bioactive constituents isolated from <em>Atractylodes lancea</em> (Thunb.) DC. rhizome exhibit synergistic effect against cholangiocarcinoma cell

Bioactive constituents isolated from <em>Atractylodes lancea</em> (Thunb.) DC. rhizome exhibit synergistic effect against cholangiocarcinoma cell

The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β‐eudesmol in human liver: Reaction phenotyping and enzyme kinetics

Atractylodes lancea (Thunb.) DC.: Ethnobotany, Phytochemistry, Pharmacological Attributes, and Safety Profile

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