Abstract
BackgroundChemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed.Methods/DesignThe study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification.ResultsPromising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO and AL), and anti-ulcer (CUR, ZO, and AL) activities.ConclusionPlants used in Thai traditional medicine for the treatment of various ailments may provide reservoirs of promising candidate chemotherapeutics for the treatment of CCA.
Highlights
Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective
Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of Atractylodes lancea thung. DC (AL) at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of Zingiber officinal Roscoe (ZO), Pra-SaPrao-Yhai formulation (PPF), and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively)
Plants used in Thai traditional medicine for the treatment of various ailments may provide reservoirs of promising candidate chemotherapeutics for the treatment of CCA
Summary
Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. Cholangiocarcinoma (CCA) is a devastating cancer with increasing worldwide incidence and mortality rate. It is an important public health problem in several parts of Southeast Asia, in the northeastern region. The discovery and development of chemotherapeutics that are effective for the treatment and control of CCA is urgently needed. In a previous study [3], we screened a total of 28 plants and 5 herbal formulations used in Thai traditional medicine for the treatment of various ailments for their cytotoxic activities against human CCA cell line CL-6. DC, fruits of Piper chaba Hunt., flowers of Mesua ferrea, and leaves of Kaemferia galangal) and 1 herbal formulation (Pra-SaPrao-Yhai) showed promising activities against CL-6 cell line with IC50 (concentration that inhibits cell growth by 50%) values of less than 50 μg/ml
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