Development of oral pharmaceutical formulation of standardized crude ethanolic extract of Atractylodes lancea (Thunb) DC.

Rattanathada, Thananchanoke; Plengsuriyakarn, Tullayakorn; Asasujarit, Rathapon; Cheoymang, Anurak; Karbwang, Juntra; Na‐Bangchang, Kesara

doi:10.5246/jcps.2020.04.027

Cited by 4 publications

(2 citation statements)

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“…The CMC capsule formulation of the crude ethanolic rhizome extract of AL (CMC-AL) was prepared by Khaolaor Laboratories Co. Ltd. under the GMP standard [ 10 ]. Water suspension of CMC-AL was prepared at three different dose levels, i.e., 1,000 (low-dose), 3,000 (medium-dose), and 5,000 (high-dose) mg/kg body weight [ 8 ].…”

Section: Methodsmentioning

confidence: 99%

“…The studies in CCA-xenografted nude mice [ 8 ] and Opisthorchis viverrini /dimethylnitrosamine-induced CCA hamsters [ 9 ] confirmed the safety and anti-CCA activity of the crude ethanolic extract of AL at all dose levels, with a significant reduction in tumor size, prolongation of survival time, and inhibition of lung metastasis, compared with 5-FU and the untreated control. Based on this non-clinical information, the capsule formulation (CMC: Chemistry, Manufacturing, and Control) of standardized extract of the crude ethanolic extract of AL was further developed for clinical studies [ 10 ]. Phase I clinical trial in healthy subjects administering a single and multiple dosing of this capsule formulation confirmed its safety profile at the maximum recommended strat dose (MRSD) [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Preclinical studies of toxicity and anti-cholangiocarcinoma activity of the standardized capsule formulation of Atractylodes lancea (Thunb.) DC

Plengsuriyakarn¹,

Kotawong²,

Karbwang³

et al. 2023

BMC Complement Med Ther

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Background Cholangiocarcinoma (CCA), the adenocarcinoma of the biliary duct, is commonly reported in Asia, with the highest incidence in northeastern Thailand. Chemotherapy of CCA has been limited by the lack of effective chemotherapeutic drugs. A series of previous in vitro and in vivo studies support further research and development of Atractylodes lancea (Thunb.) DC. (AL) as a potential candidate for treating CCA as a crude ethanolic extract. In the present study, we evaluated the toxicity and anti-CCA activity of the CMC (Chemistry, Manufacturing, and Control) capsule formulation of the ethanolic rhizome extract of AL (CMC-AL) in animals. Methods Major steps included acute, subchronic and chronic toxicity testing in Wistar rats and anti-CCA activity in a CCA-xenografted nude mouse model. The safety of CMC-AL was determined based on the maximum tolerated dose (MTD) and no-observed-adverse-effect level (NOAEL) according to the OECD guideline. The anti-CCA activity of CMC-AL in nude mice was evaluated after transplantation of CL-6 cells to evaluate inhibitory effects on tumor size progression and metastasis and survival time prolongation. Safety assessments included hematology, biochemistry parameters and histopathological examination. Lung metastasis was investigated using VEGF ELISA kit. Results All evaluations confirmed satisfactory pharmaceutical properties of oral formulation and safety profile of the CMC-AL with no overt toxicity up to the MTD and NOAEL of 5,000 and 3,000 mg/kg body weight, respectively. CMC-AL exhibited potent anti-CCA efficacy with regard to inhibitory activity on tumor progression and lung metastasis. Conclusions CMC-AL is safe and should be further investigated in a clinical trial as a potential therapy for CCA patients.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preclinical studies of toxicity and anti-cholangiocarcinoma activity of the standardized capsule formulation of Atractylodes lancea (Thunb.) DC

Plengsuriyakarn¹,

Kotawong²,

Karbwang³

et al. 2023

BMC Complement Med Ther

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The Role of Herbal Medicine in Cholangiocarcinoma Control: A Systematic Review

2022

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The growing incidence of cholangiocarcinoma (bile duct cancer) and limited treatment options stimulate a pressing demand for research and the development of new chemotherapeutics against cholangiocarcinoma. This study aimed to systematically review herbs and herb-derived compounds or herbal formulations that have been investigated for their anti-cholangiocarcinoma potential. Systematic literature searches were conducted in three electronic databases: PubMed, ScienceDirect, and Scopus. One hundred and twenty-three research articles fulfilled the eligibility critera and were included in the analysis (68 herbs, isolated compounds and/or synthetic analogs, 9 herbal formulations, and 119 compounds that are commonly found in several plant species). The most investigated herbs were Atractylodes lancea (Thunb.) DC. (Compositae) and Curcuma longa L. (Zingiberaceae). Only A. lancea (Thunb.) DC. (Compositae) has undergone the full process of nonclinical and clinical development to deliver the final product for clinical use. The extracts of A. lancea (Thunb.) DC. (Compositae), Garcinia hanburyi Hook.f. (Clusiaceae), and Piper nigrum L. (Piperaceae) exhibit antiproliferative activities against human cholangiocarcinoma cells (IC50 < 15 µg/mL). Cucurbitacin B and triptolide are herbal isolated compounds that exhibit the most promising activities (IC50 < 1 µM). A series of experimental studies (in vitro, in vivo, and humans) confirmed the anti-cholangiocarcinoma potential and safety profile of A. lancea (Thunb.) DC. (Compositae) and its active compounds atractylodin and β-eudesmol, including the capsule pharmaceutical of the standardized A. lancea (Thunb.) DC. (Compositae) extract. Future research should be focused on the full development of the candidate herbs to deliver products that are safe and effective for cholangiocarcinoma control.

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Atractylodes lancea for cholangiocarcinoma: Modulatory effects on CYP1A2 and CYP3A1 and pharmacokinetics in rats and biodistribution in mice

2022

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Atractylodes lancea (Thunb.) DC. (A. lancea: AL) is a promising candidate for the treatment of cholangiocarcinoma (bile duct cancer). The study investigated (i) the propensity of capsule formulation of the standardized extract of AL (formulated AL) to modulate mRNA and protein expression and activities of CYP1A2 and CYP3A1 in rats after long- and short-term exposure, (ii) the pharmacokinetics of atractylodin (ATD: active constituent) after long-term administration of formulated AL, and (iii) the biodistribution of atractylodin-loaded polylactic-co-glycolic acid (ATD-PLGA-NPs) in mice. To investigate CYP1A2 and CYP3A1 modulatory activities following long-term exposure, rats of both genders received oral doses of the formulated AL at 1,000 (low dose), 3,000 (medium dose), and 5,000 (high dose) mg/kg body weight daily for 12 months. For short-term effects, male rats were orally administered the formulated AL at the dose of 5,000 mg/kg body weight daily for 1, 7, 14 and 21 days. The pharmacokinetic study was conducted in male rats after administration of the formulated AL at the dose of 5,000 mg/kg body weight daily for 9 months. The biodistribution study was conducted in a male mouse receiving ATD-PLGA-NPs at the equivalent dose to ATD of 100 mg/kg body weight. The high dose of formulated AL produced an inducing effect on CYP1A2 but an inhibitory effect on CYP3A1 activities in male rats. The low dose, however, did not inhibit or induce the activities of both enzymes in male and female rats. ATD reached maximum plasma concentration (Cmax) of 359.73 ng/mL at 3 h (tmax). Mean residence time (MRT) and terminal phase elimination half-life (t1/2z) were 3.03 and 0.56 h, respectively. The extent of biodistribution of ATD in mouse livers receiving ATD-PLGA-NPs was 5-fold of that receiving free ATD. Clinical use of low-dose AL should be considered to avoid potential herb-drug interactions after long-term use. ATD-PLGA-NPs is a potential drug delivery system for cholangiocarcinoma treatment.

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Development of oral pharmaceutical formulation of standardized crude ethanolic extract of Atractylodes lancea (Thunb) DC.

Cited by 4 publications

References 0 publications

Preclinical studies of toxicity and anti-cholangiocarcinoma activity of the standardized capsule formulation of Atractylodes lancea (Thunb.) DC

Preclinical studies of toxicity and anti-cholangiocarcinoma activity of the standardized capsule formulation of Atractylodes lancea (Thunb.) DC

The Role of Herbal Medicine in Cholangiocarcinoma Control: A Systematic Review

Atractylodes lancea for cholangiocarcinoma: Modulatory effects on CYP1A2 and CYP3A1 and pharmacokinetics in rats and biodistribution in mice

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