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In vitro cytotoxic and toxicological activities of ethanolic extract of Kaempferia galanga Linn. and its active component,ethyl-p-methoxycinnamate, against cholangiocarcinoma

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Journal of Integrative Medicine 2020年第4期18卷 326-333页

作者： Porwornwisit Tritripmongkol tullayakorn plengsuriyakarn Mayuri Tarasuk Kesara Na-Bangchang Graduate Program in Bioclinical Sciences Chulabhorn International College of MedicineThammasat UniversityPathum Thani 12120Thailand Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma Chulabhorn International College of MedicineThammasat UniversityPathum Thani 12120Thailand Drug Discovery and Development Center Office of Advanced Science and TechnologyThammasat UniversityPathum Thani 12120Thailand

Objective:To evaluate the cytotoxic,apoptotic,mutagenic and immunomodulatory activities of Kaempferia galanga Linn.(KG)extract and ethyl-p-methoxycinnamate(EPMC)in ***:The present study investigated the cytotoxic[using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphe nyl-2-H-tetrazolium bromide test],apoptotic(using a mitochondrial membrane potential assay),mutagenic(using a micronucleus test)and immunomodulatory(using flow cytometry)activities of the ethanolic extract of KG and its bioactive component,EPMC,against two cholangiocarcinoma(CCA)cell lines,CL-6 and HuCCT1,and one normal human cell line,OUMS-36 T-1 ***:Both KG extract and EPMC exhibited moderate cytotoxic activity against both CCA *** cytotoxic activity was supported by their concentration-dependent induction of ***-6 was most sensitive(3–4 fold)and selective to 5-fluorouracil(5-FU),compared with KG extract and EPMC[median half inhibiting concentration(IC50)and selectivity index(SI)were 23.01 lg/mL and 17.32;78.41 lg/mL and 4.44;100.76 lg/mL and 2.20,respectively for 5-FU *** extract ***].HuCCT1 was relatively more sensitive and selective to 5-FU and EPMC than KG extract[median IC50 and SI were 66.03 lg/mL and6.04;60.90 lg/mL and 3.65;156.60 lg/mL and 2.23,respectively for 5-FU *** *** extract].EPMC produced relatively potent cytotoxic activity against polymorphonuclear cells(IC50=92.20 lg/mL).KG extract and EPMC exhibited concentration-dependent mutagenic activity,as well as inhibition of tumor necrosis factor-a and ***:Considering cytotoxic,apoptotic,immunomodulatory and mutagenic activities,further development of KG as a drug candidate is likely to focus on the oral pharmaceutical formulation of a standardized KG extract rather than isolated compounds.

关键词： Kaempferia galanga Linn. Cytotoxicity Cholangiocarcinoma Mutagenicity Apoptosis Immunomodulatory activity

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Inhibitory activities of plumbagin on cell migration and invasion and inducing activity on cholangiocarcinoma cell apoptosis

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Asian Pacific Journal of Tropical Medicine 2018年第7期11卷 430-435页

作者： Luxsana Panrit tullayakorn plengsuriyakarn Pongsakorn Martviset Kesara Na-Bangchang Drug Discovery and Development Center Thammasat University Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma Chulabhorn International College of MedicineThammasat University Graduate Program in Bioclinical Sciences Chulabhorn International College of Medicine Thammasat University Faculty of Medical Technology Rangsit University

Objective: To investigate the cytotoxic, apoptotic and inhibitory activities on cell migration and invasion of plumbagin in the human cholangiocarcinoma(CCA) cell line(CL-6) in comparison with human embryonic fibroblast cell line(OUMS). Methods: Cytotoxicity activity was evaluated using MTT assay. Inhibitory effect on cell migration and invasion were investigated using label-free real-time cell analysis and QCM ECMatrix cell invasion chamber, respectively. Apoptotic activity was evaluated using flow cytometry and Cell Event? Caspase 3/7 assay. Results: Based on results of the cytotoxicity test in CL-6 cells, 50% inhibitory concentration(IC_(50), Mean±SD) values of plumbagin and the standard drug 5-fluorouracil were(24.00±3.33) and(1 036.00±137.77) μmol/L, respectively. The corresponding values for OUMS cells were(57.00±5.23) and(2 147.00±209.98) μmol/L, respectively. The selectivity index was 2.28. The inhibitory activities of plumbagin on cell migration and invasion were potent and concentration-dependent with IC_(50) of 25.0 μmol/L and complete inhibition at 25.0 μmol/L. Flow cytometry analysis showed that plumbagin at 12.5 μmol/L(half IC_(50)) induced CL-6 cell apoptosis(43.24% of control) through stimulation of caspase 3/7 activities. Complete cell apoptosis was observed at 12.5 μmol/L. Conclusions: The cytotoxic activity and inhibition of migration and invasion including apoptosis induction in the human CCA cell line(CL-6) suggest that plumbagin could be a promising candidate for CCA chemotherapeutics. However, its relatively low selective cytotoxic effect on CCA cells is a major concern.

关键词： Cholangiocarcinoma Plumbagin Cancer migration Cancer invasion Apoptosis

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Antimalarial activity and toxicity of Garcinia mangostana Linn.

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Asian Pacific Journal of Tropical Medicine 2014年第9期7卷 693-698页

作者： Ratchanu Bunyong Wanna Chaijaroenkul tullayakorn plengsuriyakarn Kesara Na-Bangchang Chulabhorn International College of Medicine Thammasat UniversityPathumthaniThailand

Objective:To investigate the antimalarial activity and toxicity of the crude ethanolic extract of its pericarp both in vitro and in ***:The antimalarial activity of Gareinja mangostana(***)*** against 3D7 and Kl Plasmodium falciparum(***)clone were assessed using SYBR green I-based assay.A 4-day suppressive test of Plasmodium berghei{***)infected mouse was performed to investigate in vivo antimalarial ***:The in vitro antimalarial activity was seleclive(SI>5?and classified as weak and good lo moderate activity against both 3D7 and K1 ***,clones with median IC_(50)(range)values of 11.12(10.94-11.29)and 7.54(6.80-7.68)μg/mL,*** extract was considered nontoxic to *** maximum tolerated doses for acute and subacute toxicity in mice were 5 000and 2 000 mg/kg,***(range)parasite density on day 4 of the negative control group(25%Tween-80),mice treated with 250,500,1000,and 2 000 mg/kg body weight of the extract,and 10 mg/kg body weight of chloroquine for 14 d were 12.8(12.2-13.7),11.4(9.49-13.8),11.6(9.9-12.5),11.7(10.6-12.8),10.9(9.4-11.6)and 0(0-0)%*** density on day 4in the control group treated with Tween-80 was higher than the groups treated with chloroquine and all dose levels of the ***:*** linn,showed weak antimalarial activity of the extract both in vitro and in vivo could be due to limitation of absorption of the active compounds.

关键词： Garcinia mangostana Linn Plasmodium falciparum Plasmodium berghei Antimalarial activity

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

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Journal of Chinese Pharmaceutical Sciences 2020年第4期29卷 280-293页

作者： Thananchanoke Rattanathada tullayakorn plengsuriyakarn Rathapon Asasujarit Anurak Cheoymang Juntra Karbwang Kesara Na-Bangchang Graduate Program in Bioclinical Science Chulabhorn International College of MedicineThammasat UniversityPhaholyothin RoadKhlong LuangPathum Thanil2120Thailand Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma Thammasat UniversityPhaholyothin RoadKhlong LuangPathum Thani 12120Thailand Department of Pharmaceutical Sciences Faculty of PharmacyThammasat UniversityPathumthani 12120Thailand Department of Clinical Product Development Institute of Tropical MedicineNagasaki University1-12-4 SakamotoNagasaki852-8523Japan Drug Discovery and Development Center Office of Advanced Science and TechnologyThammasat UniversityPathumthani 12120Thailand

Cholangiocarcinoma(CCA), the adenocarcinoma of the biliary duct, is commonly reported in Asia with the highest incidence in northeastern Thailand. Chemotherapy of this type of cancer is limited due to the lack of effective chemotherapeutic drugs. A series of previous studies support further research and development of Atractylodes lancea(Thunb) DC.(AL) as a potential candidate for the treatment of CCA as a crude ethanolic extract. In the present study, we aimed to develop an oral pharmaceutical formulation(capsule) of the standardized AL crude ethanolic extract for further clinical development in patients with CCA. Major steps included macroscopic and microscopic authentication of the AL rhizomes, preparation of standardized AL extract, preparation of oral pharmaceutical formulation(capsule) of the standardized AL extract, quantitative and qualitative analysis of the marker compound(atractylodin) in the formulated AL extract, evaluation of contaminations of heavy metals, pesticides residues, and microorganisms in the ground AL rhizomes and the formulated(capsule) powder of AL, physicochemical and pharmaceutical properties of the formulated AL extract/capsule, and cytotoxicity evaluation of the formulated AL extract. Results of all evaluations confirmed satisfactory pharmaceutical properties of oral(capsule) formulation of the standardized AL extract.

关键词： Atractylodes lancea(Thunb)DC. Capsule formulation Atractylodin β-Eudesmol Cholangiocarcinoma

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Atractylodin-loaded PLGA nanoparticles：formulation and characterization

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中国药理学与毒理学杂志 2018年第4期32卷 244-244页

作者： Nadda MUHAMAD tullayakorn plengsuriyakarn Chuda CHITTASUPHO Kesara NA-BANGCHANG Graduate Program in Bioclinical Sciences Chulabhom International College of Medicine Thammasat University Pathum Thani 12120 Thailand Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma Chulabhom Interna

OBJECTIVE To formulate atractylodin-loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles and characterize the prepared nanoparticle *** The nanoparticle formulation was developed using solvent displacement *** encapsulation and loading efficiency were characterized and particle size,and zeta potential were determined by dynamic light scattering *** release was assessed in *** The size(mean±SD of diameter) of the prepared atractylodin-loaded PLGA nanoparticles were(161.27 ± 1.87)nm with narrow size distribution(mean PDI:0.068±0.015) and zeta potential(28.83±0.35)*** encapsulation and loading efficiency were(48.31±0.83)% and(2.15±0.04)%,*** release from atractylodin-loaded PLGA nanoparticles was observed up to(87.70±0.47)% in 72 h with biphasic ***,the nanoparticles were found to be freely dispersible in water without *** Results suggest that PLGA nanoparticles may be used as an effective drug delivery system for *** anti-cholangiocarcinoma activity of this nanoparticle formulation is required.

关键词：乙醇酸纳米粒药物治疗临床分析

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