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

Autor:	Plengsuriyakarn T; Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Thammasat University, Pathum Thani, 12120, Thailand.; Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand., Kotawong K; Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Thammasat University, Pathum Thani, 12120, Thailand., Karbwang J; Drug Discovery and Development Center, Thammasat University, Pathum Thani, 12120, Thailand., Na-Bangchang K; Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Thammasat University, Pathum Thani, 12120, Thailand. kesaratmu@yahoo.com.; Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand. kesaratmu@yahoo.com.; Drug Discovery and Development Center, Thammasat University, Pathum Thani, 12120, Thailand. kesaratmu@yahoo.com.
Jazyk:	angličtina
Zdroj:	BMC complementary medicine and therapies [BMC Complement Med Ther] 2023 Jun 07; Vol. 23 (1), pp. 186. Date of Electronic Publication: 2023 Jun 07.
DOI:	10.1186/s12906-023-03992-z
Abstrakt:	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. (© 2023. The Author(s).)
Databáze:	MEDLINE
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